Bruno D. Fornage

Role of preoperative ultrasonography in the surgical management of patients with thyroid cancer.

BACKGROUND Cervical recurrence occurs in up to 30% of patients with differentiated thyroid carcinoma. We retrospectively compared preoperative transcutaneous ultrasonography and physical examination (PE) results in the detection of local-regional metastases (lymph node and soft tissue) in patients with thyroid cancer. METHODS Data were collected retrospectively from the medical records of patients with thyroid carcinoma who underwent preoperative ultrasonography. Patients were divided into 3 groups: group 1, those undergoing primary thyroid/neck surgery; group 2, those undergoing reoperation for persistent disease; and group 3, those undergoing reoperation for recurrent thyroid carcinoma. For each group, we recorded the frequencies with which ultrasonography detected disease in a neck compartment (central or lateral) that was normal on PE. RESULTS Two hundred twelve patients underwent operation for primary, persistent, or recurrent papillary (n=130), medullary (n=61), or follicular/Hürthle cell (n=21) carcinoma. Ultrasonography detected additional sites of metastatic disease not appreciated on PE in 21 (20%) of 107 group 1 patients, 9 (32%) of 28 group 2 patients, and 52 (68%) of 77 group 3 patients. The surgical procedure performed was altered by the information obtained from preoperative ultrasonography in 82 (39%) of the 212 patients. Of the 107 group 1 patients, cervical recurrence has been detected in only 6 (6%) at a median follow-up of 36 months, in spite of 67 (63%) having tumors larger than 2 cm or lymph node metastases. CONCLUSIONS Preoperative high-quality ultrasonography detected lymph node or soft-tissue metastases in neck compartments believed to be uninvolved by PE in 39% of patients. Ultrasound findings altered the operative procedure in these patients, facilitating complete resection of disease and potentially minimizing local-regional recurrence.

Outcome After Pathologic Complete Eradication of Cytologically Proven Breast Cancer Axillary Node Metastases Following Primary Chemotherapy

PURPOSE Pathologic complete remission (pCR) of primary breast tumors after primary chemotherapy (PCT) is associated with higher relapse-free survival (RFS) and overall survival (OS) rates. The purpose of this study was to determine long-term outcome in patients achieving pCR of cytologically proven axillary lymph node (ALN) metastases. METHODS Patients with cytologically documented ALN metastases were treated in five prospective PCT trials. After surgery, patients were subdivided into those with and without residual ALN carcinoma. Survival was calculated by the Kaplan-Meier method. RESULTS Of 925 patients treated, 403 patients had cytologically confirmed ALN metastases. Eighty-nine patients (22%) achieved ALN pCR after PCT. Compared with the group without ALN pCR, 5-year OS and RFS were improved in patients achieving ALN pCR (93% [95% CI, 87.5 to 98.5] and 87% [95% CI, 79.7 to 94.3] v 72% [95% CI, 66.5 to 77.5] and 60% [95% CI, 54.1 to 65.9], respectively; P < .0001). Residual primary tumor did not affect outcome of those with ALN pCR. Combination anthracycline/taxane-based PCT resulted in significantly more ALN pCRs, although outcome after ALN pCR was not improved by taxanes. We constructed a nomogram demonstrating that patients who do not benefit from neoadjuvant anthracyclines are unlikely to benefit from subsequent taxanes. CONCLUSION ALN pCR is associated with an excellent prognosis, even with a residual primary tumor, pointing to biologic differences between primary and metastatic cells. ALN pCR represents an early surrogate marker of long-term outcome. Response to initial PCT has important potential as a guide to subsequent therapy.

Significant long-term survival after radiofrequency ablation of unresectable hepatocellular carcinoma in patients with cirrhosis.

BackgroundRadiofrequency ablation (RFA) offers an alternative treatment in some unresectable hepatocellular carcinoma (HCC) patients with disease confined to the liver. We prospectively evaluated survival rates in patients with early-stage, unresectable HCC treated with RFA.MethodsAll patients with HCC treated with RFA between September 1, 1997, and July 31, 2002, were prospectively evaluated. Patients were treated with RFA by using a percutaneous or open intraoperative approach with ultrasound guidance and were evaluated at regular intervals to determine disease recurrence and survival.ResultsA total of 194 patients (153 men [79%] and 41 women [21%]) with a median age of 66 years (range, 39–86 years) underwent RFA of 289 sonographically detectable HCC tumors. All patients were followed up for at least 12 months (median follow-up, 34.8 months). Percutaneous and open intraoperative RFA was performed in 140 (72%) and 54 (28%) patients, respectively. The median diameter of tumors treated with RFA was 3.3 cm. Disease recurred in 103 (53%) of 194 patients, including 69 (49%) of 140 patients treated percutaneously and 34 (63%) of 54 treated with open RFA (not significant). Local recurrence developed in nine patients (4.6%). Most recurrence was intrahepatic. The overall complication rate was 12%. Overall survival rates at 1, 3, and 5 years for all 194 patients were 84.5%, 68.1%, and 55.4%, respectively.ConclusionsTreatment with RFA can produce significant long-term survival rates for cirrhotic patients with early-stage, unresectable HCC. RFA can be performed in these patients with relatively low complication rates. Confirmation of these results in randomized trials should be considered.

Thermoacoustic and photoacoustic tomography of thick biological tissues toward breast imaging

Microwave-based thermoacoustic tomography (TAT) and laser-based photoacoustic tomography (PAT) in a circular scanning configuration were both developed to image deeply seated lesions and objects in biological tissues. Because malignant breast tissue absorbs microwaves more strongly than benign breast tissue, cancers were imaged with good spatial resolution and contrast by TAT in human breast mastectomy specimens. Based on the intrinsic optical contrast between blood and chicken breast muscle, an embedded blood object that was 5 cm deep in the tissue was also detected using PAT at a wavelength of 1064 nm.

Cortical Morphologic Features of Axillary Lymph Nodes as a Predictor of Metastasis in Breast Cancer: In Vitro Sonographic Study

OBJECTIVE The purpose of this study was in vitro sonographic-pathologic correlation of findings in dissected axillary lymph nodes from breast cancer patients undergoing axillary lymph node dissection and classification of the sonographic appearance of the nodes on the basis of cortical morphologic features to facilitate early recognition of metastatic disease. MATERIALS AND METHODS High-resolution sonography was used for in vitro examination of 171 lymph nodes from 19 axillae in 18 patients with unknown nodal status who underwent axillary lymph node dissection for early infiltrating breast cancer. The images were evaluated by two blinded observers, and discordant readings were referred to a third blinded observer. Each lymph node was classified as one of types 1-6 according to cortical morphologic features. Types 1-4 were considered benign, ranging from hyperechoic with no visible cortex to thickened generalized hypoechoic cortical lobulation. Type 5 (focal hypoechoic cortical lobulation) and type 6 (hypoechoic node with absent hilum) nodes were considered metastatic. The reference standard for metastatic disease was histopathologic evaluation of sectioned nodes by a single pathologist blinded to sonographic findings. Largest nodal diameter also was measured. RESULTS Interobserver agreement was 77% for classification of nodal morphology (types 1-6) and 88% for characterization of a node as benign or malignant. Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of cortical shape in prediction of metastatic involvement of axillary nodes were 77%, 80%, 36%, 96%, and 80%. Type 4 nodes had the most false-negative findings (four of 36). Node size ranged from 0.2 to 3.8 cm, and subcentimeter nodes of all types were detected. CONCLUSION In breast cancer, axillary lymph nodes can be classified according to cortical morphologic features. Predominantly hyperechoic nodes (types 1-3) can be considered benign. Generalized cortical lobulation (type 4) is uncommonly a false-negative finding, but metastasis, if present, is invariably detected at sentinel node mapping. The presence of asymmetric focal hypoechoic cortical lobulation (type 5) or a completely hypoechoic node (type 6) should serve as a guideline for universal performance of fine-needle aspiration for preoperative staging of breast cancer. This classification, when verified with larger samples, may serve as a useful clinical guideline if proven with results of in vivo studies.

Impact of Clinicopathological Factors on Sensitivity of Axillary Ultrasonography in the Detection of Axillary Nodal Metastases in Patients With Breast Cancer

Background: Ultrasonography and fine-needle aspiration (FNA) are used to evaluate the breast and regional nodes in breast cancer patients. We sought to identify factors influencing the sensitivity of ultrasonography for detection of nodal metastasis.Methods: Patients with a clinically negative axilla who underwent axillary ultrasonography and sentinel lymph node biopsy were included.Results: Of 208 patients, axillary ultrasonography was negative in 180 (86%) and suspicious or indeterminate in 28 (14%). FNA was performed in 22 patients whose findings were indeterminate or suspicious, and 3 were positive for malignancy. Final pathological examinations revealed positive nodes in 53 patients: 39 (22%) of 180 with negative ultrasonographic findings and 14 (50%) of 28 with indeterminate or suspicious ultrasonographic findings (P = .001). Excisional biopsy was more common for patients with indeterminate or suspicious findings on preoperative ultrasonography (P = .038). There were no significant differences in tumor size, histological features, size of nodal metastasis, or number of positive nodes between patients whose ultrasonography findings were negative and those whose findings were indeterminate or suspicious.Conclusions: Ultrasonographically suggested nodal metastasis is associated with the finding of nodal disease on final pathological examination. No significant clinicopathologic criteria were found to impact sensitivity of ultrasonography; however, excisional biopsy for diagnosis may be a confounding variable in subsequent axillary ultrasonography.

ULTRASOUND AS A COMPLEMENT TO MAMMOGRAPHY AND BREAST EXAMINATION TO CHARACTERIZE BREAST MASSES

This study was designed to determine if complementary ultrasound (US) imaging and Doppler could decrease the number of biopsies for benign masses. A total of 761 breast masses were sequentially scored on a level of suspicion (LOS) of 1-5, where 1 represented low, and 5 was a high suspicion of malignancy, for mammography, US, and color flow with pulse Doppler (DUS). After biopsy, the results were analyzed using 2 x 2 contingency tables and ROC analysis, for mammography alone and in combination with US and DUS. The addition of US increased the specificity from 51.4% to 66.4% at a prevalence of 31.3% malignancy. ROC analysis showed that the addition of US significantly improved the performance over mammography alone in women < 55 years old (p = 0.049); > 55 years old (p = 0.029); masses < 1 cm (p = 0.016) and masses > 1 cm (p = 0.016). These results show that the addition of US to mammography alone could substantially reduce the number of breast biopsies for benign disease.

Radiofrequency ablation of early-stage invasive breast tumors: an overview.

As the management of breast cancer evolves toward less invasive treatments, the next step is the possibility of removing the primary tumor without surgery. The most promising of the noninvasive ablation techniques is radiofrequency ablation, which uses frictional heating that is caused when ions in the tissue attempt to follow the changing directions of a high-frequency alternating current. Three pilot studies, including an ongoing study at M.D. Anderson Cancer Center, have demonstrated that radiofrequency ablation is effective for the destruction of small primary breast cancers. The most important factorfor successful radiofrequency ablation is accuracy of the ultrasound evaluation, which is used to estimate tumor size, localize the tumor for treatment, and monitor the progress of the ablation. A study in preparation at M.D. Anderson will determine whether the use of radiofrequency ablation alone for the local treatment of primary breast cancer will result in outcomes equivalent to those obtained with breast conservation therapy.

Role of axillary lymph node dissection after tumor downstaging with induction chemotherapy for locally advanced breast cancer

AbstractBackground: Induction chemotherapy has become the standard of care for patients with locally advanced breast cancer (LABC) and currently is being evaluated in prospective clinical trials in patients with earlier-stage disease. To better gauge the role of axillary lymph node dissection in patients with LABC this study was performed to assess initial axillary status on physical and ultrasound examination, axillary tumor downstaging following induction chemotherapy, and the accuracy of physical examination compared with axillary sonography in predicting which patients will have axillary lymph node metastases found on pathologic examination. Methods: Between 1992 and 1996, 147 consecutive patients with LABC were registered in a prospective trial of induction chemotherapy using 5-fluorouracil, doxorubicin, and cyclophosphamide. Physical and ultrasound examinations of the axilla were performed at diagnosis and after induction chemotherapy. Segmental resection with axillary lymph node dissection or modified radical mastectomy was performed, followed by postoperative chemotherapy and irradiation of the breast or chest wall and regional lymphatics. Results: Following induction chemotherapy, 43 (32%) of the 133 patients with clinically positive lymph nodes on initial examination had axillary tumor downstaging as assessed by physical and ultrasound examination. The sensitivity of axillary sonography in identifying axillary metastases was significantly higher than that of physical examination (62% vs. 45%,P=.012). The specificity of physical examination (84%) was higher than that of sonography (70%), but the difference did not reach statistical significance. Among the 55 patients in whom the findings of both physical and ultrasound examination of the axilla were negative following induction chemotherapy, 29 patients (53%) were found to have axillary lymph node metastases on pathologic examination of the axillary contents. However, 28 (97%) of these patients had either 1 to 3 positive lymph nodes or only micrometastases 2 to 5 mm in diameter. Conclusions: Preoperative clinical assessment of the axilla by physical examination combined with ultrasound examination is not completely accurate in predicting metastases in patients with LABC following tumor downstaging. However, patients with negative findings on both physical and ultrasound examinations of the axilla may be potential candidates for omission of axillary dissection if the axilla will be irradiated because minimal axillary disease remains. Patients who have positive findings on preoperative physical or ultrasound examinations should receive axillary dissection to ensure local control. A prospective randomized trial of axillary dissection versus axillary radiotherapy in patients with a clinically negative axilla following induction chemotherapy is currently underway.

Sonographically guided needle biopsy of nonpalpable breast lesions

This article describes the techniques of sonographically guided fine‐needle aspiration (FNA) and core‐needle biopsy (CNB) of nonpalpable breast lesions. Virtually any nonpalpable breast lesion that is clearly demonstrated on sonograms can be sampled with a needle under ultrasound guidance. Advantages of ultrasound‐guided FNA include its pinpoint accuracy, the excellent tolerance by patients, and the ability to aspirate or inject fluid or air. Advantages of ultrasound‐guided CNB include a near 100% tissue recovery rate even in fibrous masses, the ability to assess the invasiveness of a cancer, and the fact that tissue cores are readily interpreted by any pathologist. In institutions in which an expert cytopathologist is available, FNA is often used as a first‐line biopsy technique, with CNB being reserved for situations in which FNA cannot provide a definitive answer to the question asked. In most institutions, however, CNB has become the standard for percutaneous needle biopsy of breast masses, and sonography has replaced stereotaxy as the standard guidance technique for nonpalpable masses.