Nagi F. Khouri

Computed tomography of bronchiectasis

Computed tomography (CT) was performed on six patients with bronchiectasis. In two cases of advanced cystic bronchiectasis, the diagnosis was apparent on plain chest roentgenograms. In four cases, bronciectasis was initially diagnosed by CT and later confirmed by bronchography. The CT signs of bronchiectasis include air-fluid levels in distended bronchi, a linear array or cluster of cysts, dilated bronchi in the periphery of the lung, and bronchial wall thickening due to peribronchial fibrosis. Distended bronchi must be distinguished from emphysematous blebs, which generally have no definable wall thickness and no accompanying vessels. It is concluded that CT should have a role in establishing the presence and anatomic extent of bronchiectasis.

Computed tomography of the pulmonary parenchyma. Part 2: Interstitial disease

A series of patients with documented predominantly interstitial pulmonary disease was examined by routine and high-resolution computed tomography (CT) and compared to a series of twenty-one normals. Inspiratory-expiratory lung density measurements were also obtained at predetermined levels. Several basic CT signs of interstitial disease were identified: (1) finely irregular and thickened pleural surfaces; (2) irregular vascular shadows; (3) thickened and irregular bronchial walls making bronchi visible over a longer portion of their course in the lungs; (4) reticular network of lines with three patterns easily distinguishable by the size of their reticular element; (5) hazy patches of increased density of various sizes distinguishable from alveolar filling processes by the fact that vessels can still be visualized through them; and (6) nodules of various sizes. Micronodules are often associated with a small or medium-size reticular network and in most cases seem to represent points of confluence rather than isolated nodules. The hematogenous origin of some nodules can be specifically suggested when feeding vessels arc demonstrated on thin-section scans. Nodules associated with a large network of thickened septa are suggestive of lymphangitic carcinomatosis. Inspiratory-expiratory density gradients can be more useful in confirming the diagnosis of interstitial disease than absolute measurements.

Typical and atypical CT manifestations of pulmonary sarcoidosis.

Chest CT of 36 patients with proven sarcoidosis were reviewed retrospectively. In all cases CT was obtained in an attempt to answer a diagnostic dilemma, either a patient with abnormal chest radiography and no clinical diagnosis or a patient with a history of known sarcoidosis and an atypical presentation on chest radiography. Computed tomography was superior to chest radiography in detecting and defining the presence of adenopathy. In addition, CT was more accurate in detecting the presence and extent of infiltrates. Secondary findings in sarcoidosis including pleural effusions, bullous disease, bronchiectasis, cavitation with and without mycetoma, and fibrosing mediastinitis were detected using CT. Using the information obtained from CT, we were able to arrive at the correct diagnosis in the majority of cases and to decide which modality would be most useful to secure tissue confirmation (bronchoscopy, transtracheal biopsy, or percutaneous needle biopsy of a solitary mass).

The Role of Ultrasound-Guided Fine-Needle Aspiration of Axillary Nodes in the Staging of Breast Cancer

BackgroundAs a complement to sentinel node dissection (SLND), we evaluated ultrasound-guided fine-needle aspiration (USFNA) of normal and abnormal axillary nodes in breast cancer patients. We hypothesized that USFNA would be accurate for primary breast tumors larger than 2 cm.MethodsWe retrospectively reviewed 68 patients who underwent 69 preoperative USFNAs from 2003 to 2005. The results of 65 preoperative USFNA were compared with the results of SLND or axillary node dissection (ALND) for concordance. Four USFNAs were excluded from analysis because of a complete response to neoadjuvant therapy. We evaluated whether primary tumor features (histology, size, grade, vascular invasion, estrogen/progesterone receptor status and Her-2-neu status) predicted concordance of USFNA results and the final lymph node pathology.ResultsOf 65 axillae analyzed, 39 (60%) were positive, four (6%) were non-diagnostic, and 22 (34%) were negative by USFNA. USFNA had 89% sensitivity, 100% specificity, and 100% positive predictive value (PPV) in patients with palpable or ultrasonographically suspicious nodes. USFNA sensitivity dropped significantly for nonpalpable, ultrasonographically normal nodes (54%), while specificity and PPV remained 100%. None of the primary tumor features predicted concordance of USFNA and SLND/ALND.ConclusionsUSFNA of axillary nodes has a high specificity and PPV in clinically or radiologically suspicious nodes. Sensitivity of USFNA is low for nodes of normal appearance, but positive USFNA may allow definitive management of the axilla without a SLND. Thus, USFNA of normal appearing nodes might be beneficial in cases where decisions regarding neoadjuvant chemotherapy would be affected by the results.

An Evaluation of Bone Scans as Screening Procedures for Occult Metastases in Primary Breast Cancer

Preoperative bone scans were obtained in 104 patients with operable breast cancer. Areas of increased radioactivity detected by the bone scan were correlated with appropriate radiographs. One of 64 patients (1.5%) with clinical Stage I and Stage II breast cancer had a metastatic lesion detected by the preoperative bone scan. In contrast, 10 of 41 patients (24%) with Stage III breast cancer had occult metastatic lesions detected by the preoperative bone scan. The majority of patients with abnormal bone scans and no radiographic evidence of a benign lesion to explain the cause of the increased radioactivity proved to have metastatic breast cancer on follow-up examination. Even though 20% of patients with operable breast cancer will eventually develop bone metastases, our results indicate that preoperative bone scans are not an effective means of predicting which patients with Stage I and Stage II disease will develop metastatic breast cancer. Because of the considerably increased frequency of detection of occult metastases in patients with Stage III breast cancer, bone scans should be obtained routinely in the preoperative assessment of these patients.

Multiparametric Magnetic Resonance Imaging, Spectroscopy and Multinuclear (23Na) Imaging Monitoring of Preoperative Chemotherapy for Locally Advanced Breast Cancer

RATIONALE AND OBJECTIVES The aim of this prospective study was to investigate using multiparametric and multinuclear magnetic resonance imaging during preoperative systemic therapy for locally advanced breast cancer. MATERIALS AND METHODS Women with operable stage 2 or 3 breast cancer who received preoperative systemic therapy were studied using dynamic contrast-enhanced magnetic resonance imaging, magnetic resonance spectroscopy, and ²³Na magnetic resonance. Quantitative metrics of choline peak signal-to-noise ratio, total tissue sodium concentration, tumor volumes, and Response Evaluation Criteria in Solid Tumors were determined and compared to final pathologic results using receiver-operating characteristic analysis. Hormonal markers were investigated. Statistical significance was set at P < .05. RESULTS Eighteen eligible women were studied. Fifteen responded to therapy, four (22%) with pathologic complete response and 11 (61%) with pathologic partial response. Three patients (17%) had no response. Among estrogen receptor-positive, HER2-positive, and triple-negative phenotypes, observed frequencies of pathologic complete response, pathologic partial response, and no response were 2, 5, and 0; 1, 4, and 0; and 1, 1, and 3, respectively. Responders (pathologic complete response and pathologic partial response) had the largest reductions in choline signal-to-noise ratio (35%, from 7.2 ± 2.3 to 4.6 ± 2; P < .01) compared to nonresponders (11%, from 8.4 ± 2.7 to 7.5 ± 3.6; P = .13) after the first cycle. Total tissue sodium concentration significantly decreased in responders (27%, from 66 ± 18 to 48.4 ± 8 mmol/L; P = .01), while there was little change in nonresponders (51.7 ± 7.6 to 56.5 ± 1.6 mmol/L; P = .50). Lesion volume decreased in responders (40%, from 78 ± 78 to 46 ± 51 mm³; P = .01) and nonresponders (21%, from 100 ± 104 to 79.2 ± 87 mm³; P = .23) after the first cycle. The largest reduction in Response Evaluation Criteria in Solid Tumors occurred after the first treatment in responders (18%, from 24.5 ± 20 to 20.2 ± 18 mm; P = .01), with a slight decrease in tumor diameter noted in nonresponders (17%, from 23 ± 19 to 19.2 ± 19.1 mm; P = .80). CONCLUSIONS Multiparametric and multinuclear imaging parameters were significantly reduced after the first cycle of preoperative systemic therapy in responders, specifically, choline signal-to-noise ratio and sodium. These new surrogate radiologic biomarkers maybe able to predict and provide a platform for potential adaptive therapy in patients.

Incidental minimal atypical lobular hyperplasia on core needle biopsy: correlation with findings on follow-up excision.

IntroductionAtypical lobular hyperplasia (ALH), often an incidental finding in breast core biopsies, is largely considered to be a risk factor for carcinoma rather than a direct precursor. However, management of ALH is controversial. We review our experience with incidental minimal ALH on core biopsy, and correlate with excision and follow-up results. DesignWe evaluated all cases of ALH on core biopsy from 1999 to 2009 from our institution, focusing on cases with ≤3 foci of ALH (minimal), paired excision, and no other lesion on the core biopsy that by itself would require excision. Cases with discordant clinical/radiologic impressions, suggesting that a suspicious lesion had been missed on biopsy, were excluded. Therefore, the excisions were performed because of the diagnosis of ALH. ResultsOf 56 cases with ALH on biopsy and paired excision, 42 showed minimal ALH. On excision, 26 had residual ALH and 13 were benign. Three cases had other atypical lesions: lobular carcinoma in situ (2 cases) and mild atypical ductal hyperplasia separate from the biopsy site (1 case). On follow-up, only 1 patient developed subsequent ALH in the same breast. No other ipsilateral lesions were later diagnosed (mean follow-up 3.2 y). ConclusionsNo case with ALH on biopsy had a lesion on excision requiring further treatment, suggesting that these patients can be managed more conservatively. Furthermore, no patients were diagnosed with a higher grade lesion in the same breast on follow-up. We propose that, if there is close radiologic correlation and follow-up, minimal incidental ALH on core biopsy (≤3 foci) does not require excision.

Preclinical and Clinical Evaluation of Intraductally Administered Agents in Early Breast Cancer

Intraductal administration of chemotherapeutic agents may reduce new breast cancer formation and offer a less toxic treatment regimen than intravenous therapy. Repairing the Ductwork Breast cancer is typically treated intravenously with chemotherapeutic drugs, poisons that permeate the entire body and cause toxic side effects, such as hair loss, pain, and nausea. Because most breast tumors originate in the cellular lining of the breast ducts, Stearns and colleagues designed a gentler, more local treatment regimen that gets right to the source: intraductal drug injection. The authors first tested intraductal treatment with five different chemotherapeutic agents, including paclitaxel and doxorubicin, on rats with mammary tumors, at doses comparable to what might be used in the clinic in actual patients. Compared to saline-treated or untreated control animals, the rats treated intraductally had fewer tumors in the mammary glands, with minimal side effects. Stearns et al. then enrolled 17 women in a phase 1 clinical trial to examine intraductal treatment using one chemical agent, pegylated liposomal doxorubicin. Their localized delivery to the breast ducts resulted in considerably lower systemic concentrations of the drug compared to intravenous administration, suggesting that the intraductal approach is a less toxic alternative to standard chemotherapy. This clinical trial also indicates that approved agents can be delivered to the breast ducts in an outpatient setting. Longer-term studies in more women will be necessary to determine the efficacy of intraductal chemotherapy. Intraductal treatment could be especially useful for women with premalignant lesions or those at high risk of developing breast cancer, thus drastically improving upon their other, less attractive options of breast-removal surgery or surveillance (termed “watch and wait”). It’s not yet routine practice, but direct treatment of the breast ductwork with cancer-fighting drugs promises to be a safer, less painful method for controlling cancer. Most breast cancers originate in the epithelial cells lining the breast ducts. Intraductal administration of cancer therapeutics would lead to high drug exposure to ductal cells and eliminate preinvasive neoplasms while limiting systemic exposure. We performed preclinical studies in N-methyl-N′-nitrosourea–treated rats to compare the effects of 5-fluorouracil, carboplatin, nanoparticle albumin-bound paclitaxel, and methotrexate to the previously reported efficacy of pegylated liposomal doxorubicin (PLD) on treatment of early and established mammary tumors. Protection from tumor growth was observed with all five agents, with extensive epithelial destruction present only in PLD-treated rats. Concurrently, we initiated a clinical trial to establish the feasibility, safety, and maximum tolerated dose of intraductal PLD. In each eligible woman awaiting mastectomy, we visualized one ductal system and administered dextrose or PLD using a dose-escalation schema (2 to 10 mg). Intraductal administration was successful in 15 of 17 women with no serious adverse events. Our preclinical studies suggest that several agents are candidates for intraductal therapy. Our clinical trial supports the feasibility of intraductal administration of agents in the outpatient setting. If successful, administration of agents directly into the ductal system may allow for “breast-sparing mastectomy” in select women.

Multiparametric and Multinuclear Magnetic Resonance Imaging of Human Breast Cancer: Current Applications

The exploration of novel imaging methods that have the potential to improve specificity for the identification of malignancy is still critically needed in breast imaging. Changes in physiologic alterations of soft tissue water associated with breast cancer can be visualized by magnetic resonance (MR) imaging. However, it is unlikely that a single MR parameter can characterize the complexity of breast tissue. Techniques such as multiparametric MR imaging, proton magnetic resonance spectroscopic (MRSI) imaging, and 23Na sodium MR imaging when used in combination provide a comprehensive data set with potentially more power to diagnose breast disease than any single measure alone. A combination of MR, MRSI, and 23Na sodium MR parameters may be examined in a single MR imaging examination, potentially resulting in improved specificity for radiologic evaluation of malignancy.

Computed tomography of lobar collapse: 1. Endobronchial obstruction.

The computed tomographic (CT) appearance of lobar collapse has yet to be defined. In an attempt to determine the characteristic appearance of collapse 95 cases were reviewed retrospectively in a wide variety of clinical settings over a 3 year period ending January 1983. In this report 38 cases of lobar collapse secondary to endobronchial occlusion are analyzed; the appearance of collapse without endobronchial obstruction forms the basis of a subsequent report. Computed tomography was accurate in determining the site of bronchial occlusion in all cases. In 36 of 38 cases collapse was caused by endobronchial tumors, including bronchogenic carcinoma, bronchial carcinoids, endobronchial metastases, and lymphoma. Differentiation between these tumors was not feasible with CT. Most cases of collapse were caused by central tumor. In those cases in which a bolus of contrast material was used differentiation between tumor mass and collapsed pulmonary parenchyma was possible. Two of 38 cases were found to have benign bronchial occlusion. In one case a mucous plug obstructing the left lower lobe bronchus was accurately defined. In another case a bronchial stricture occluded the right lower lobe bronchus. This represented the only false positive case in this series. It is concluded that CT is an accurate means for establishing the diagnosis of endobronchial obstruction. In most cases the diagnosis of neoplasia was possible, provided a bolus of contrast material was used to define tumor mass. The potential role of CT in evaluating patients with lobar collapse is discussed.