Bassam I. Aswad

Intraoperative Triple Antenna Hepatic Microwave Ablation

OBJECTIVE Microwave ablation is emerging as a new treatment option for patients with unresectable hepatic malignancies. This two-center study shows the results of a phase 1 clinical trial of patients with known hepatic masses who underwent synchronous triple antenna microwave ablation before elective hepatic resection. SUBJECTS AND METHODS Intraoperative microwave ablation was performed before hepatic resection. Hepatic lesions were targeted using real-time intraoperative sonography with three microwave antennas positioned in a triangular configuration. Microwave ablation was performed at 45 W for 10 minutes. Hepatic resection was then completed in the standard fashion. Gross specimens were sectioned and measured to determine tumor and ablation sizes. Representative areas were stained with H and E stain and vital histochemical nicotinamide adenine dinucleotide (NADH) stain. RESULTS Ten patients with a mean age of 64 years (range, 48-79 years) were treated. Tumor histology included colorectal carcinoma metastases and hepatocellular carcinoma. The mean maximal tumor diameter was 4.4 cm (range, 2.0-5.7 cm). The mean maximal ablation diameter was 5.5 cm (range, 5.0-6.5 cm), while the average ablation zone volume was 50.8 cm3 (range, 30.3-65.5 cm3). Gross and microscopic examinations of areas after microwave ablation showed clear coagulation necrosis, even surrounding large hepatic vessels (> 3 mm in diameter). A marked thermallike effect was observed with maximal intensity closest to the antenna sites. NADH staining confirmed the uniform absence of viable tumor in the ablation zone. CONCLUSION This study shows the feasibility of using multiple microwave antennas simultaneously in the treatment of liver tumors intraoperatively. Additional percutaneous studies are currently under way to investigate the safety and efficacy in treating nonsurgical candidates.

Cryptogenic and Secondary Organizing Pneumonia: Clinical Presentation, Radiographic Findings, Treatment Response, and Prognosis

BACKGROUND Organizing pneumonia (OP) is a distinct clinical and pathologic entity. This condition can be cryptogenic (COP) or secondary to other known causes (secondary OP). In the present study, we reviewed the features associated with COP and secondary OP in patients from two teaching hospitals. METHODS The medical records of 61 patients with biopsy-proven OP were retrospectively reviewed. Forty patients were diagnosed with COP and 21 patients with secondary OP. The clinical presentation, radiographic studies, pulmonary function tests (PFTs), laboratory data, BAL findings, treatment, and outcome were analyzed. RESULTS The mean age at presentation was 60.46 ± 13.57 years. Malaise, cough, fever, dyspnea, bilateral alveolar infiltrates, and a restrictive pattern were the most common symptoms and findings. BAL lymphocytosis was observed in 43.8% of patients with OP. The relapse rate and mortality rate after 1 year of follow-up were 37.8% and 9.4%, respectively. The in-hospital mortality was 5.7%. The clinical presentation and radiographic findings did not differ significantly between patients with COP and secondary OP. A mixed PFT pattern (obstructive and restrictive physiology) and lower blood levels of serum sodium, serum potassium, platelets, albumin, protein, and pH were observed among patients with secondary OP. Higher blood levels of creatinine, bilirubin, Paco₂, and BAL lymphocytes were also more common among patients with secondary OP. There were no differences in the relapse rate or mortality between patients with COP and secondary OP. The 1-year mortality correlated with an elevated erythrocyte sedimentation rate, low albumin, and low hemoglobin levels. CONCLUSIONS The clinical and radiographic findings in patients with COP and secondary OP are similar and nonspecific. Although certain laboratory abnormalities are more common in secondary OP and can be associated with worse prognosis, they are likely due to the underlying disease. COP and secondary OP have similar treatment response, relapse rates, and mortality.

Gastrointestinal malignancies in patients with celiac sprue

BACKGROUND Celiac sprue is a malabsorption disease, which carries an increased risk of gastrointestinal malignancy, often underestimated. The purpose of this study was to examine the management of patients with gastrointestinal neoplasms complicating celiac disease. PATIENTS AND METHODS The pathology database at our institution was searched from 1986 to present; and the literature from 1966 to 1997 was reviewed to identify reports of celiac sprue complicated by malignancy. A total of 82 cases were available for analysis. RESULTS Two thirds of patients had carried the diagnosis of celiac sprue for a mean of approximately 10 years. The remaining one third were diagnosed with celiac disease and gastrointestinal malignancy simultaneously. Jejunal T-cell lymphoma was the most common malignancy. There was also an increased frequency of small intestinal adenocarcinoma and squamous cell carcinoma of the esophagus. Prognosis was generally poor, related to the histologic type and stage of the disease. CONCLUSIONS Gastrointestinal malignant neoplasms, especially small bowel lymphomas, can occur in patients with celiac sprue. Patients with known celiac disease who present with exacerbation of symptoms should be promptly investigated for occult gastrointestinal malignancies, and considered for early surgical exploration.

Marrow cell genetic phenotype change induced by human lung cancer cells.

Microvesicles have been shown to mediate varieties of intercellular communication. Work in murine species has shown that lung-derived microvesicles can deliver mRNA, transcription factors, and microRNA to marrow cells and alter their phenotype. The present studies evaluated the capacity of excised human lung cancer cells to change the genetic phenotype of human marrow cells. We present the first studies on microvesicle production by excised cancers from human lung and the capacity of these microvesicles to alter the genetic phenotype of normal human marrow cells. We studied 12 cancers involving the lung and assessed nine lung-specific mRNA species (aquaporin, surfactant families, and clara cell-specific protein) in marrow cells exposed to tissue in co-culture, cultured in conditioned media, or exposed to isolated lung cancer-derived microvesicles. We assessed two or seven days of co-culture and marrow which was unseparated, separated by ficoll density gradient centrifugation or ammonium chloride lysis. Under these varying conditions, each cancer derived from lung mediated marrow expression of between one and seven lung-specific genes. Microvesicles were identified in the pellet of ultracentrifuged conditioned media and shown to enter marrow cells and induce lung-specific mRNA expression in marrow. A lung melanoma and a sarcoma also induced lung-specific mRNA in marrow cells. These data indicate that lung cancer cells may alter the genetic phenotype of normal cells and suggest that such perturbations might play a role in tumor progression, tumor recurrence, or metastases. They also suggest that the tissue environment may alter cancer cell gene expression.

Intraoperative Microwave Ablation of Pulmonary Malignancies with Tumor Permittivity Feedback Control: Ablation and Resection Study in 10 Consecutive Patients

PURPOSE To determine histologic changes induced by microwave ablation (MWA) in patients with pulmonary malignancy by using an ablation system with tumor permittivity feedback control, enabling real-time modulation of energy power and frequency. MATERIALS AND METHODS Institutional review board approval and patient informed consent were obtained for this prospective HIPAA-complaint ablation and resection study. Between March 2009 and January 2010, 10 patients (four women, six men; mean age, 71 years; age range, 52-82 years) underwent intraoperative MWA of pulmonary malignancies. Power (10-32 W) and frequency (908-928 MHz) were continuously adjusted by the generator to maintain a temperature of 110°-120°C at the 14-gauge antenna tip for one 10-minute application. After testing for an air leak, tumors were resected surgically. Gross inspection, slicing, and hematoxylin-eosin (10 specimens) and nicotinamide adenine dinucleotide (six specimens) staining were performed. RESULTS Tumors included adenocarcinomas (n = 5), squamous cell carcinomas (n = 3), and metastases from endometrial (n = 1) and colorectal (n = 1) primary carcinomas. Mean maximum tumor diameter was 2.4 cm (range, 0.9-5.0 cm), and mean maximum volume was 8.6 cm(3) (range, 0.5-52.7 cm(3)). One air leak was detected. Five of 10 specimens were grossly measurable, revealing a mean maximum ablation zone diameter of 4.8 cm (range, 3.0-6.5 cm) and a mean maximum ablation zone volume of 15.1 cm(3) (range, 7.3-25.1 cm(3)). At hematoxylin-eosin staining, coagulation necrosis was observed in all ablation zones, extended into the normal lung in nine of 10 specimens, and up to blood vessel walls without evidence of vessel (>4 mm) thrombosis. Nicotinamide adenine dinucleotide staining enabled confirmation of no viability within ablation zones extending into normal lung in five of six specimens. CONCLUSION MWA with tumor permittivity feedback control results in cytotoxic intratumoral temperatures and extension of ablation zones into aerated peritumoral pulmonary parenchyma, possibly forming the equivalent of an oncologic resection margin.

Lobectomy by Video-Assisted Thoracic Surgery vs Muscle-Sparing Thoracotomy for Stage I Lung Cancer: A Critical Evaluation of Short- and Long-Term Outcomes

BACKGROUND Propensity-matched studies have shown lobectomy by VATS to be superior to thoracotomy. However, these studies do not control for institution or surgeon expertise and do not compare VATS strictly with muscle-sparing thoracotomy (MST). STUDY DESIGN From a single surgeon experienced in both VATS and MST, patients undergoing lobectomy for clinical stage I non-small cell cancer were evaluated. Video-assisted thoracic surgery was chosen if the patient requested this approach, otherwise MST was used. Short-term and long-term outcomes were compared. RESULTS From 2007 to 2012, two hundred and ninety-eight patients were evaluated, 74 (25%) VATS and 224 (75%) MST. There were no statistically significant differences in demographics, chest tube days, and postoperative complications between the 2 surgical groups. Operative time was longer for VATS (median 130 minutes for VATS vs 90 minutes for MST; p<0.001). Hospital length of stay was longer for MST (median 4.5 days for VATS vs 5 days for MST; p=0.007). There was no difference in disease-free survival (5-year: 76% for VATS vs 78% for MST; p=0.446) and overall survival (5-year: 80% for VATS vs 79% for MST; p=0.840) for clinical stage I disease. Results were unchanged using propensity score matching of 60 VATS and 60 MST patients for postoperative complications, disease-free survival, and overall survival between the 2 matched groups. CONCLUSIONS Our current comparison of VATS vs MST, from a single surgeon experienced with both approaches, found operative time (favoring MST) and hospital days (favoring VATS) to be the only difference between the 2 groups; and major outcomes, such as postoperative complications, disease-free survival, and overall survival, were not different. A multi-institution randomized trial should be considered before deeming any one approach to be superior.

Pleuropericarditis in a Patient with Inflammatory Bowel Disease: A Case Presentation and Review of the Literature

Inflammatory bowel disease (IBD) can affect the lung parenchyma and airways. Rarely it involves the pleural space and pericardium, causing inflammatory exudative pleural and/or pericardial effusions. In this report, we describe a 76-year-old patient with recurrent sterile exudative pleuropericarditis that gradually responded to treatment with steroids, and we review the relevant literature. Thoracic serositis in patients with IBD can cause pleuritis, pericarditis, pleuropericarditis, or myopericarditis. This is a relatively rare presentation of the uncommon and probably underreported and underrecognized pulmonary extraintestinal manifestations of IBD. Pleuropericardial inflammatory disease and effusion can be directly related to IBD, its complications, associated infections, or the medications used to treat it. Serositis directly related to IBD is a diagnosis of exclusion. It is important to evaluate the pleural effusion and rule out other etiologies before making this diagnosis. Pleural or pericardial biopsies are rarely necessary, and probably show nonspecific acute and chronic inflammatory changes. Although the specific pathophysiology of pleuropericardial disease in patients with IBD remains unclear, the response to systemic steroids is usually adequate.

HER-2/neu gene amplification in stages I-IV breast cancer detected by fluorescent in situ hybridization.

Purpose: Approximately 25–30% of breast and ovarian carcinomas have amplification of the HER-2/neu oncogene. The aim of the present study was to focus on HER-2/neu gene amplification in different clinical stages of breast cancer in order to (1) determine if fluorescent in situ hybridization (FISH) can be used to detect HER-2/neu gene amplification in different clinical stages of breast cancer, (2) establish whether HER-2/neu gene amplification characterizes a subset of breast cancer in each of these stages, and (3) determine whether a trend for correlation of amplification with the clinical stage of the disease can be detected using the FISH technology.Methods: A total of 40 specimens of formalin-fixed, paraffin-embedded breast cancer tissues were analyzed cytogenetically, in a blinded fashion, for HER-2/neu gene amplification using FISH and the Vysis LSI HER-2/neu Orange and CEP 17 Green DNA dual color probe. The criterion for “high amplification” was an amplification ratio of >4.0, that for “moderate amplification” a ratio between 2.1 and 4.0, and that for “low amplification” a ratio of 1.5–2.0.Results: Using a cutoff point of ≥1.5, the overall frequency of HER-2/neu gene amplification among stage I tumors was 30% (3 out of 10). Of these, one-third (1 out of 3) showed low amplification, one-third (1 out of 3) were moderately amplified, and one-third (1 out of 3) were highly amplified. The overall frequency of HER-2/neu gene amplification among stage II tumors was 0% (0 out of 10). The overall frequency of HER-2/neu gene amplification among stage III tumors was 10% (1 out of 10). The sole tumor found positive was classified as moderately amplified by our criteria. The overall frequency of HER-2/neu gene amplification among stage IV tumors was 50% (5 out of 10). Four of the 5 tumors found positive were highly amplified. The overall frequency of gene amplification in the 40 cases studied was 22.5% (9 out of 40 tumors studied).Conclusion: Although a linear correlation between HER-2/neu amplification and clinical stage cannot be established at this time, it is interesting to note that when stages I and II, and when stages III and IV are combined, respectively, the latter category has a higher amplification frequency than the former. Furthermore, stage IV has the highest frequency (5 out of 10) of HER-2/neu gene amplification than all three lower stages combined (4 out of 30). This is no doubt due to the high frequency of gene amplification observed in stage IV tumors, which, interestingly, also demonstrate high level amplification of HER-2/neu gene copy numbers. Although the biologic and clinical basis for gene amplification is not clear, given the observation that the most aggressive disease stage is associated with the highest frequency of gene amplification and the most high level amplification, further exploration of HER-2/neu as a prognostic marker of poor outcome using FISH is warranted.

Evaluation of mulitprobe radiofrequency technology in a porcine model

OBJECTIVE We evaluated two new radiofrequency devices in an in vivo porcine model. MATERIALS AND METHODS Multiprobe radiofrequency ablation (RFA) was used in a porcine model with an impedance-based algorithm in one experiment and clustered probes with and without switcher controllers in another; a Pringle maneuver was used with half of the ablations. RESULTS The impedance experiment included 13 ablations, with a mean length of 7.0 cm and width of 2.9 cm (95% CI) and an average time of 596 s. Ablation volumes were significantly larger (54.1+/-11.7 cc(3) vs 34.9+/-4.8 cc(3), p<0.05) and ablation times were significantly shorter (359 s vs 834 s, p<0.05) for the Pringle group compared with the No Pringle group, respectively. The switcher controller experiment included 34 RFAs. Diameter (mm) (51.4 vs 40.3, p<0.0001), surface area (cm(2)) (22.4 vs 16.0, p<0.0002), and volume (cc) (66.1 vs 36.9, p<0.0001) were significantly larger for the combination probes with switcher controller compared with clustered probes, respectively. Ablation volumes for the Pringle vs No Pringle groups in the combination probes were 68.0 cc vs 64.3 cc and for the clustered probes 40.1 cc vs. 33.7 cc, respectively. CONCLUSION Multiprobe ablations using RFA are promising technologies that need further study to evaluate their clinical utility.

Long-term survival after pneumonectomy for primary pulmonary malignant melanoma.

As few as 30 cases of primary malignant melanoma of the lung have been reported in the literature. Many patients die within months of diagnosis; few published cases describe patients who survive long-term after treatment. We report a case of primary pulmonary malignant melanoma in a patient who remains disease-free 60 months after pneumonectomy.