CT for detection of malignant posterior intercostal lymph nodes in patients undergoing pre-operative staging for malignant pleural mesothelioma.

INTRODUCTION: Recent evidence suggests that patients with malignant pleural mesothelioma (MPM) undergoing extended pleurectomy/decortication (eP/D) with metastasis to the posterior intercostal lymph nodes (PILN) have a worse prognosis. In this study, we determine if MPM PILN metastasis can be reliably detected on computed tomography (CT). MATERIALS AND METHODS: Preoperative staging CT exams were reviewed for the presence of PILN in MPM patients undergoing eP/D between 2007-2013 with surgical sampling of their PILN. CT images were reviewed by two thoracic radiologists blinded to clinical records, including operative pathology reports. The number and short axis size of PILN were recorded and correlated with surgical pathology. Statistical analysis examined the value of preoperative CT to detect metastatic PILN. RESULTS: Of 36 patients that underwent eP/D with PILN sampling had preoperative CT images for review. At surgery, 22 of these patients had metastatic PILN and 14 had benign PILN. The positive and negative predictive values for one or more nodes seen on preoperative CT were 60 % and 38 % respectively. The number of PILN on preoperative CT did not predict metastasis (p = 0.40) with an average of 2 PILN seen, regardless of PILN pathology. The average nodal short axis size was 4.6 mm and 4.8 mm for benign and malignant PILN, respectively, and PILN short axis size did not predict metastasis (p = 0.39). There was little inter-observer variability between the size and number of nodes detected by each radiologist. CONCLUSIONS: CT does not reliably identify metastatic PILN on preoperative CT for patients with MPM undergoing extended pleurectomy/decortication.

Trial of a novel synthetic sealant in preventing air leaks after lung resection.

BACKGROUND: Postoperative air leaks are a major cause of morbidity after lung resections. This study was designed to evaluate the efficacy and safety of a new synthetic, bioresorbable surgical sealant in preventing air leaks after pulmonary resection. METHODS: In a multicenter trial, 172 patients undergoing thoracotomy were randomized intraoperatively in a 2:1 ratio to receive surgical sealant applied to sites at risk for air leak after standard methods of lung closure (treatment group) or to have standard lung closure only (control group). The primary outcome variable was the percentage of patients free of air leakage throughout hospitalization. Secondary outcome variables were the control of air leaks intraoperatively and the time to postoperative air leak cessation. Time to chest tube removal, time to hospital discharge, and safety outcomes were also evaluated. RESULTS: Air leaks were identified before randomization in 89 of 117 patients in the treatment group and in 39 of 55 patients in the control group. Application of the sealant resulted in control of air leaks in 92% of treated patients (p < or = 0.001). A significantly higher percentage of treated patients than control patients remained free of air leaks during hospitalization (39% versus 11%, p < or =0.001). The mean times to last observable air leak were 30.9 hours in the treatment group and 52.3 hours in the control group (p = 0.006). In the treatment group, trends were observed for reduced time to chest tube removal and earlier discharge. No significant difference was identified in postoperative morbidity and mortality between the two groups. CONCLUSIONS: Air leaks after lung resection occur in most patients. The application of this novel surgical sealant appears to be effective and safe in preventing postoperative air leaks.

In vitro effects of photodynamic therapy on Aspergillus fumigatus.

Photodynamic therapy is a technique for killing cells with visible light after pretreatment with a photosensitizing agent. We demonstrated significant in vitro fungicidal activity against Aspergillus fumigatus of the photosensitizer Green 2W, activated with 630 nm light. This effect was both inoculum- and light dose-dependent. At a Green 2W concentration of 31.5 mg/L, there was complete killing of 2.7 x 10(1) cfu/mL with a light dose of 110 J/cm(2) and up to 2.7 x 10(6) cfu/mL with a light dose of 385 J/cm(2).

Changing clinical course of patients with malignant mesothelioma: implications for FNA cytology and utility of immunocytochemical staining.

The diagnosis of both local recurrences and distant metastases of mesothelioma can be accomplished by fine-needle aspiration (FNA) biopsy. Although the previous history of mesothelioma provides strong support for recurrent/metastatic mesothelioma, other diagnostic possibilities (particularly adenocarcinoma) may require exclusion via special stains in some cases. In this study, we report on the morphologic findings in 13 cases of mesothelioma which underwent FNA (7 metastatic lesions, 6 local recurrences). In addition, immunohistochemical staining results for 7 cases with available material using antibodies directed against cytokeratin AE 1/3 and two antibodies reported to show consistently positive results in mesothelioma (calretinin and cytokeratin 5/6) are reported and compared to results seen for 10 cases of adenocarcinoma. All cases of mesothelioma and adenocarcinoma showed strong staining with cytokeratin AE 1/3. Three of 7 cases of mesothelioma showed strong staining with calretinin, while only focal staining was detected in 3 additional cases; only one case showed positive staining with cytokeratin 5/6. One of 10 cases of adenocarcinoma showed calretinin positivity; however, at least focal staining with cytokeratin 5/6 was seen in 4 cases. These results suggest that cytokeratin 5/6 is neither a sensitive nor specific stain for the diagnosis of mesothelioma in cytology material. Calretinin appears to be more specific for mesothelioma but showed disappointing sensitivity for this tumor, potentially limiting its diagnostic utility in FNA material.

Toxicity of photodynamic therapy after combined external beam radiotherapy and intraluminal brachytherapy for carcinoma of the upper aerodigestive tract.

BACKGROUND AND OBJECTIVE: To describe the toxicity of photodynamic therapy (PDT) in patients with carcinoma of the upper aerodigestive tract who received prior treatment with external beam irradiation and intraluminal brachytherapy (IB). STUDY DESIGN/MATERIALS AND METHODS: Hospital records of PDT patients were reviewed. Three patients who received prior treatment with external beam irradiation and IB were identified. Two patients had esophageal carcinoma treated with combined chemotherapy and external beam irradiation (55.8 and 50.4 Gy) followed by IB (12 Gy and 35 Gy at 1 cm). These patients then received PDT for treatment of recurrence (2 mg/kg Photofrin injection and 2 light applications: 630 nm, 150--200 J/cm, 200--400 mW/cm). One patient had non-small cell lung cancer treated with external beam irradiation (60 Gy) followed by IB (36.1 Gy at 1 cm) and then received PDT for recurrence (1 mg/kg Photofrin injection and one light application: 630 nm, 150 J/cm, 200 mW/cm). RESULTS: One patient with esophagus cancer had formation of a tracheoesophageal fistula, which required stent placement. The other esophageal cancer patient developed quadriplegia due to an epidural abscess arising from a fistula with the diseased portion of the esophagus. The lung cancer patient had massive hemoptysis after the procedure and died 2 days later. Autopsy showed necrotizing arteritis of the right pulmonary artery. CONCLUSION: Patients with upper aerodigestive tract carcinoma who have received treatment with both external beam irradiation and IB seem to be at higher risk for complications when treated with PDT.

Endobronchial photodynamic therapy for the treatment of lung cancer.

After 2 decades of basic research and clinical experience with endobronchial photodynamic therapy, clear indications for its use have arisen. PDT for the treatment of superficial NSCLC is a viable alternative for patients with inoperable lung cancer. Although early indications are that it may be used to spare operable patients an aggressive surgical procedure, this application still should be considered investigational. The standard of care remains surgical resection in the operable patient. PDT may be considered for the palliation of obstructing lesions of the tracheobronchial tree; however, the risk for prolonged sensitivity to sunlight limits its broad application in this patient population. As better screening techniques are introduced, the role of PDT will expand in the future management of superficial lung cancers. Future developments include new photosensitizers with decreased duration of sun sensitivity and greater choice of wavelength to affect depth of penetration, better dosimetry systems for more consistent light delivery and reporting of results, and better light delivery systems for more homogenous distribution of light.

Lobectomy with tangential pulmonary artery resection without regard to pulmonary function.

BACKGROUND: Non-small cell carcinoma of the lung invading the pulmonary artery (PA) has traditionally been treated by pneumonectomy. Although PA resection and reconstruction (PAR) has begun to gain acceptance, previous series of PAR by the simplest technique of tangential excision and primary repair have been unfavorable. We have maintained a policy of performing PAR preferentially whenever anatomically feasible, and usually this has been possible by tangential excision and primary repair. This study sought to determine if this approach is sound. METHODS: Retrospective clinical and pathologic review. RESULTS: Thirty-three PARs were performed from 1992 to 1999. The patients, followed 6 to 65 months (mean 25), were aged 36 to 80 years (mean 61), and their tumors were pathologic stage IB (n = 7), IIB (n = 13), IIIA (n = 9), and IIIB (n = 4). The mean preoperative forced expiratory volume in 1 second was 70% predicted. The procedures included 14 bronchial sleeve lobectomies with PAR and 19 simple lobectomies with PAR. The PARs were performed without heparinization and included 19 tangential excisions with primary closure, 11 larger tangential excisions with pericardial patch closure, and 3 sleeve resections. There were no operative deaths and 2 (6.1%) early major complications, all unrelated to the PAR. Thirteen patients (39%) had early minor complications. Four-year Kaplan-Meier survival was 48.3% for stages I/II and 45% for stage III. Ipsilateral, central, intrathoracic recurrence occurred in 3 patients (9.1%). CONCLUSIONS: These data are not dramatically different from those reported for standard resections. Although the numbers are small, the results suggest that lobectomy with PAR by tangential excision is an acceptable alternative to pneumonectomy whenever anatomically possible.

Secondary pulmonary malignancy.

Patients with pulmonary metastases were previously relegated to palliative medical management. Since the first metastasectomies in the nineteenth century, general acceptance of this technique has occurred. Although, initially, indications for resection of pulmonary metastases were limited to patients with solitary nodules, over time, indications have broadened to include multiple lesions, recurrent disease, and nearly all histologies. With appropriate patient selection and the absence of extrathoracic disease, survival may be improved. For patients with disseminated and symptomatic disease, surgical therapy may also provide some relief.

Non-small cell lung cancer: prognostic factors in patients treated with surgery and postoperative radiation therapy.

PURPOSE: To determine survival outcomes, to identify adverse prognostic factors for relapse, and to compare American Joint Commission on Cancer (AJCC) staging systems in patients with non-small cell lung cancer (NSCLC) treated with surgery and postoperative radiation therapy. MATERIALS AND METHODS: Between 1980 and 1995, 211 patients with NSCLC underwent surgery and postoperative radiation therapy. Surgery consisted of wedge resection (12.5%), lobectomy (67.8%), or pneumonectomy (19.7%). Pathologic stages (1992 AJCC) included I (n = 22), II (n = 70), IIIA (n = 104), and IIIB (n = 12). Indications for radiation therapy included compromised margins (n = 81) and/or positive mediastinal nodes (n = 55). Prognostic factors were identified by using univariate and multivariate models. RESULTS: Overall 3-year survival for patients with stage I, II, and IIIA cancer was 58.9%, 44.1%, and 43.2%, respectively. Older age (P = .008), male sex (P = .021), large primary tumor (P = .004), and multiple positive mediastinal nodes (P = .046) were associated with worse rates of survival. Actuarial risk of local-regional relapse (36 patients) was 21.4% at 3 years. In a multivariate model, use of wedge resection (P = .001), positive margins (P = .010), and larger pathologic tumor (P = .059) were risk factors for local-regional recurrence. Actuarial rate of distant failure was 55.2% at 3 years. CONCLUSION: Local-regional control can be achieved with surgery and radiation therapy in approximately 80% of patients; however, the rate of distant metastasis remains unacceptably high. Other variables, such as multiple positive nodes, may serve to identify patients at higher risk for relapse and poorer survival. Methods for improving treatment outcomes in these patients should be pursued.

Clinical presentation of stage IIIA (N2) non-small cell lung cancer: role of multimodality therapy.

Neoadjuvant chemotherapy before surgical resection of locally advanced non-small cell lung cancer (NSCLC) has been shown to improve survival compared with surgery alone in several randomized clinical trials. A case report is presented describing the use of paclitaxel and carboplatin in a multimodality regimen for a patient with stage IIIA N2 NSCLC. Studies are ongoing to determine the optimal type and timing of chemotherapy.

Comparison of open and thoracoscopic bilateral volume reduction surgery: complications analysis.

BACKGROUND: The effectiveness of lung volume reduction for the treatment of patients with emphysema is well established, but data about the surgical approach, the postoperative management, and complications are limited. We report a comparison of patients undergoing bilateral lung volume reduction (BLVRS) via median sternotomy and thoracoscopic techniques with emphasis on hospital course and complications. METHODS: All patients undergoing BLVRS at Hospital of University of Pennsylvania were analyzed for mortality and morbidity, using a combination of prospective data analysis and retrospective chart review. RESULTS: Patients undergoing BLVRS via median sternotomy were older than those undergoing video-assisted thoracoscopic surgery (VATS) procedures (63.9+/-6.89 vs 59.3+/-9.4 years, p = 0.005). Operating time was longer for the VATS procedure (147 versus 129 minutes, p = 0.006) while estimated blood less was greater for median sternotomy (209 versus 82 L, p = 0.0000017). Significant differences were found in intensive care unit stay, days intubated, life-threatening complications, respiratory complications, requirement for tracheostomy, and death that favored VATS BLVRS. When only later cohorts of patients were compared, more life-threatening complications and deaths were found in patients undergoing BLVRS by median sternotomy. There were no differences between early and late median sternotomy BLVRS patients. Twenty-six percent of the lethal complications in median sternotomy BLVRS patients were bowel perforations, equally divided between duodenal ulcers and colons. CONCLUSIONS: Managing patients after BLVRS remains complex. Bilateral video-assisted volume reduction offers equivalent functional outcome with potentially decreased morbidity and mortality. Gastrointestinal perforations can complicate the management of these patients.

Epidemiology of lung cancer.

Lung cancer is the leading cause of cancer deaths for men and women in the United States, accounting for more cancer deaths since 1930 than all other cancer deaths combined. Whereas primary lung cancer was a relatively rare malignancy in the early 1900s, in 1994 there were approximately 170,000 new cases of lung cancer in the United States, of which roughly 100,000 were in men and 70,000 were in women. Despite numerous medical and surgical advances in the past several decades, there has not been a dramatic increase in the percentage of patients being cured of this lethal disease. Smoking is the primary factor responsible for the lung cancer epidemic, but there are numerous other environmental and genetic factors that have been implicated in the pathogenesis of the disease. Recently, it has become evident that passive smoking may also play a significant role in the development of lung cancer. Although screening has not been proven effective in the past, it may be time to reevaluate this technique because early detection of lung cancer affords the best chance for cure.

The role of surgery in the multimodality management of non-small cell lung cancer.

The majority of patients with lung cancer have disseminated disease at the time of presentation. For the minority of patients with disease localized to the chest, the concept of staging becomes particularly important because it has a major impact on the treatment plan. Guided by findings on the computed tomographic scan, mediastinoscopy remains the definitive invasive staging procedure to document unequivocally the involvement of the mediastinal lymph nodes. Equally as important is the documentation of absence of disease in contralateral lymph nodes. Patients with locally advanced non-small cell lung cancer, especially those with involvement of mediastinal lymph nodes (N2), are candidates for a multimodality approach to treatment involving either chemotherapy alone or in combination with radiation therapy. Surgical excision may be important in the management of these patients after an induction regimen. If surgical excision is performed, complete excision is the single most important factor. Postoperative adjuvant therapy may reduce the incidence of local recurrence but has not been shown to improve survival.

The role of radiation therapy in the management of non-small cell lung cancer.

Lung cancer remains the number one cancer killer for both men and women in the United States. Most patients with lung cancer will receive radiotherapy as part of their treatment. For non-small cell lung cancer, this treatment will be administered as either neoadjuvant, adjuvant, definitive, or palliative therapy. Occasionally the distinction between these classifications may be unclear or may change in the course of the treatment. The use of thoracic radiotherapy as part of the treatment regimen and the goal of the therapy depends not just on tumor-related factors such as stage, but also on patient-related factors such as pulmonary reserve and performance status. This article describes the use of radiotherapy in each of the previously listed capacities and details the potential benefits and complication of this treatment modality for non-small cell lung cancer.

A quantitative model of invasive Pseudomonas infection in burn injury.

To evaluate newer therapies for wound infections, it becomes necessary to quantify bacteria that invade from the infected wounds into the adjacent tissues. For example, antibody-targeted photolysis targets the invasive Pseudomonas with antibodies carrying photochemical dyes. A full-thickness burn wound was infected with Pseudomonas aeruginosa with a modification of previous methods. In mice, a skin fold was elevated, and two preheated brass blocks at 92 degrees to 95 degrees C were applied for 5 seconds, producing a 5% total body surface area injury with discrete margins. The eschars were immediately inoculated with Pseudomonas. Survival at 10 days was 100% with burn injury alone and 60% with infected burns. Pseudomonas (10(8)/gm) were recovered from the unburned muscle by 24 hours. The method produced uniform and reproducible quantitative bacteriology within the muscle immediately beneath the burn injury (SL < 0.05). Quantitative comparisons can be used to determine the effectiveness of newer modalities to control Pseudomonas burn wound infections.

Circulating interleukin-1 beta and tumor necrosis factor-alpha concentrations after burn injury in humans.

OBJECTIVES: To measure plasma interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF alpha) concentrations after burn injury and to determine if these concentrations relate to clinical status. DESIGN: Prospective assessment. SETTING: Hospital burn unit. PATIENTS: Thirty-one patients with second- or third-degree burns, covering 10% to 95% of body surface area. MEASUREMENTS AND MAIN RESULTS: Initial concentrations of IL-1 beta were increased (mean 188 +/- 31 pg/mL), and the concentrations for each patient correlated with body temperature at the time of the blood sample (rho = 0.51, p < .015) (rho is a nonparametric statistical measure; a nonparametric analysis is mandatory for data that is categorical [Acute Physiology and Chronic Health Evaluation, APACHE, scores] and data that are not normally distributed [IL-1 beta and tumor necrosis factor, TNF, data]). Mean TNF alpha concentrations were initially 264 +/- 132 pg/mL, and these concentrations were positively related to body temperature (rho = 0.41, p < .05) and inversely related to the total WBC count (rho = -0.45, p < .025). Through the course of hospitalization, plasma cytokine levels fluctuated, but transient increases (sometimes into the nanogram/mL range) did not consistently correspond to changes in clinical signs or severity of illness, as determined by APACHE II scores. The maximum plasma cytokine levels in any patient were not related to age, but maximum IL-1 beta concentrations were inversely related to burn size (rho = -0.46, p < .015). The final IL-1 beta concentrations measured in the patients who died (n = 7) were significantly less than measurements in surviving patients matched for burn size and age taken at approximately the same time after admission. CONCLUSIONS: These results indicate that early after burn injury there is a correspondence of IL-1 beta and TNF alpha with certain host responses, but these correlations disappear with the progression of illness. In general, IL-1 beta and TNF alpha appear to be poor indicators of prognosis during burn injury; however, the association of mortality with low circulating IL-1 beta values supports the concept of IL-1 beta as being an essential mediator of host defenses.

Hepatocytes from rat liver perfusions. Physicochemical effects on polyribosome size.

Hepatocytes have been used extensively both in vitro and in vivo for a wide variety of studies. Although isolated hepatocytes appear similar to their in vivo counterparts, they are different in some respects. One aspect in which they differ is their ability to translate proteins. The isolation process appears to inflict sufficient damage to reduce the average polyribosome size within the isolated hepatocytes and this size reduction correlates with a lower rate of protein production. Two methods of liver perfusion that better maintain the normal distribution of polyribosomes are described in this report. It is clear from these studies that new isolation methods that result in high yields of viable hepatocytes that function maximally are needed.