Preoperative lymph node staging of early-stage cervical carcinoma by [18F]-fluoro-2-deoxy-D-glucose-positron emission tomography

BACKGROUND: Increasing evidence has documented the value of positron emission tomography (PET) in oncology, but only limited data are available comparing PET findings with the pathologic status of regional lymph nodes in patients with cervical carcinoma. The objective of this study was to determine the sensitivity and specificity of PET in detecting lymph node metastasis in women with early-stage cervical carcinoma. METHODS: The authors performed a retrospective review of all patients with Stage IA-IIA cervical carcinoma who underwent PET before surgery from 1999 to 2004. The status of the regional lymph nodes was correlated with lymph node pathology. RESULTS: Fifty-nine patients were identified. Pelvic lymph node metastases were present in 32% of the patients and were detected by PET with a sensitivity of 53%, a specificity of 90%, a positive predictive value (PPV) of 71%, and a negative predictive value (NPV) of 80%. Paraaortic lymph node disease was present in 9% of patients and was detected by PET with a sensitivity of 25%, a specificity 98%, a PPV of 50%, and an NPV of 93%. The mean size of the tumor deposits was larger in the PET-positive pelvic nodes (15.2 mm; range, 2-35 mm) than in the PET-negative lymph nodes (7.3 mm; range, 0.3-20 mm; P = 0.002). Computed tomography (CT) scans were obtained before surgery in 42 patients. The combined sensitivity of PET and CT in these patients was 75%. PET alone detected 9 (36%) of the positive lymph node groups, whereas CT alone detected 3 (12%) of the positive lymph node groups. Neither PET nor CT detected the positive lymph node groups in 8 patients (32%). CONCLUSIONS: Pathologic validation of PET imaging demonstrated a low sensitivity and a high specificity for PET in patients with early-stage cervical carcinoma.     

Axillary lymph node management in breast cancer with positive sentinel lymph node biopsy

The surgical treatment of localized breast cancer has become progressively less aggressive over the years. The management of the axillary lymph nodes has been modified by the introduction of sentinel lymph node biopsy. Axillary dissection can be avoided in patients with sentinel lymph node negative biopsies. Based on randomized trials data, it has been proposed that no lymph node dissection should be carried out even in certain patients with sentinel lymph node positive biopsies. This commentary discusses the basis of such recommendations and cautions against a general omission of lymph node dissection in breast cancer patients with positive sentinel lymph node biopsies. Instead, an individualized approach based on axillary tumor burden and biology of the cancer should be considered.     

Positron emission tomography and sentinel lymph node dissection in breast cancer

Sentinel lymph node dissection (SLND) is emerging as the preferred method of axillary staging for breast cancer patients. To further the use of noninvasive techniques in breast cancer, positron emission tomography (PET) scans have been considered as an alternative axillary staging modality. In order to compare the 2 modalities, we studied 15 invasive breast cancer patients who had undergone a preoperative PET scan before sentinel lymphadenectomy. PET scans were compared to axillary pathology results, which were defined as the greatest diameter of nodal metastases. Primary tumor sizes ranged from 0.5 cm to 5.0 cm (median,1.5 cm) and all were ductal in origin except for 1 invasive lobular and 1 mucinous carcinoma. Ten women had completion axillary dissections. Sentinel lymph node dissection was successful in all patients with completion dissections and no false-negative results. Five patients had sentinel node metastases, but PET scans identified only 1 of these patients, resulting in 4 false-negative PET scans. Missed metastases ranged in size from a micrometastatic focus identified only by immunohistochemistry to a nodal tumor measuring 11 mm in diameter. In addition, 1 woman with a PET-positive axilla was tumor free by SLND and remains free of axillary recurrence 29 months postoperatively. Two women had mediastinal uptake by PET scanning and were found to be tumor free after computerized tomography. The results of this preliminary study suggest that PET scanning using current techniques can be used as an adjunct to SLND rather than as an alternative staging technique.     

18F-2-fluoro-2-deoxy-d-glucose positron emission tomography in staging of locally advanced breast cancer.

PURPOSE: To prospectively evaluate the effect of adding whole-body (18)F-2-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) to conventional screening for distant metastases in patients with locally advanced breast cancer (LABC). PATIENTS AND METHODS: All women with LABC referred for participation in the LABC Spinoza trial were considered eligible for this study. Patients were included if chest x-ray, bone scan, liver ultrasound, or computed tomography scan performed by the referring physician failed to reveal distant metastases. They underwent whole-body FDG PET scanning before therapy. Patients with subsequently proven distant metastases were switched to alternative forms of chemotherapy, hormonal therapy, or both. RESULTS: Among the 48 patients evaluated with PET, 14 had abnormal FDG uptake, and metastases were suspected in 12. After simple clinical evaluation (plain x-ray, history), 10 sites that were suggestive of abnormality remained. Further work-up revealed that four sites were metastases. Proven false positivity occurred in one patient with sarcoidosis. In the other five patients, the reason for abnormal FDG uptake (liver, lung, bone) remained unclear, and patients were treated as planned. Eleven months later, distant metastases were found in one patient at sites unrelated to the previous FDG uptake. CONCLUSION: The addition of FDG PET to the standard work-up of patients with LABC may lead to the detection of unexpected distant metastases. This may contribute to a more realistic stratification between patients with true stage III breast cancer and those who are in fact suffering from stage IV disease. Abnormal PET findings should be confirmed to prevent patients from being denied appropriate treatment.     

Pitfalls in lymph node staging with positron emission tomography in non-small cell lung cancer patients

BACKGROUND: The evidence of clinical value of positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (FDG) in lymph node (LN) staging in non-small cell lung cancer (NSCLC) has been shown in numerous papers. However, few studies have assessed its limitations. The aim of the present study is to clarify clinico-pathologic factors responsible for false PET results. METHODS: From July 2000 through December 2001, 71 NSCLC patients underwent both FDG PET and surgical intervention at the National Cancer Center Hospital East, Chiba. Clinical records, computed tomographic (CT) scan findings, PET findings, and histologic findings were retrospectively reviewed. RESULTS: Sensitivity, specificity, accuracy in nodal staging for CT were 29, 83, and 65% and for PET were 39, 79, and 66%, respectively. There were 10 (14%) false-positive PET scans and 14 (20%) false-negative PET scans. The causative factors for false-positive PET scan were: (1) inflammatory conditions in seven patients; (2) PET mis-localization of an interlobar LN as a mediastinal LN in one patient; (3) inability to distinguish the endobronchial polypoid growth of a primary tumor from a lobar LN in one patient; (4) unknown in one patient. All false-positive LNs due to inflammatory conditions showed reactive lymphoid hyperplasia histologically. The causative factors for false-negative PET scan were: (1) limitation of spatial resolution of the PET scanner in 12 patients (maximum tumor focus dimensions in false-negative LNs ranging from 1 to 7.5 mm, with an average of 3.4 mm); (2) PET mis-localization of a mediastinal LN as a hilar LN in one patient; (3) weak FDG uptake by microscopic tumor foci due to necrosis with massive bleeding in a metastatic LN in one patient. CONCLUSIONS: Inflammatory conditions were most responsible for false-positive PET scans, and spatial resolution limitation of FDG PET was the causative factor of false-negative PET scans. Recognizing these factors in advance would be clinically helpful in accurate nodal staging with FDG PET.     

Axillary lymph node irradiation in breast cancer: state of the art

Place of axillary radiotherapy in the management of patients with breast cancer remains debated. While the prognostic value of axillary lymph node extension has been largely demonstrated, the benefit of axillary treatment is more uncertain. Large clinical trials having demonstrated the benefit of adjuvant radiotherapy in advanced breast cancer comprised large nodal irradiation, including axillary area. Analyzing the true benefit of axillary radiotherapy is rendered difficult by heterogeneity of series, particularly when focusing on the extent of lymph node dissection. Although adjuvant axillary radiotherapy is usually recommended in patients with insufficient lymph node dissection or with bulky axillary involvement, the prognosis in these patients remains poor by metastatic evolution and such strategy exposes to increased toxicity and functional sequels. Further assessments should better define the optimal indications and the true benefit of axillary radiotherapy.     

Minimal invasive staging for breast cancer: clinical experience with sentinel lymph node biopsy

During the 1990s, considerable research and development resulted in reasonably reliable methods to target the set of lymph nodes most likely to contain metastases in patients with breast cancer. The methods of identification of these "sentinel nodes" (SNs) involve injection of a visual-based dye or a radioactive tracer. The tracer/dye enters the lymphatics and labels the SNs so that they can be selectively removed. SNs can be successfully identified in > or =90% of patients. In breast cancer patients with clinically negative lymph nodes, the accuracy of the SNs to predict whether any nodal metastases are present is > or =97%. The false-negative rate, however, ranges from 0% (in smaller series) to 11%. Clinical trials are in progress that will determine the long-term safety and predictive value of SN resection in patients with breast cancer. Successful application of SN surgery should allow elimination of conventional axillary lymphadenectomy in at least 75% of patients with breast cancer. Semin Oncol 28:229-235.     

Comparative efficacy of positron emission tomography and ultrasonography in preoperative evaluation of axillary lymph node metastases in breast cancer

PURPOSE: In primary breast cancer, axillary nodal status is the most powerful predictive factor of recurrence. However, axillary lymph node dissection may cause surgical complications. If preoperative evaluation of axillary lymph node metastases is possible, unnecessary axillary lymph node dissections can be avoided. The purpose of this study was to evaluate the efficacy of positron emission tomography (PET) on detection of axillary lymph node metastases in breast cancer. METHODS: PET scans of the axilla were obtained in 32 patients with primary breast cancer. All patients fasted for at least 4 hours before the examination. After transmission scans for attenuation correction were performed, emission scans after intravenous injection of 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) were obtained. RESULTS: Overall accuracy of PET alone, ultrasonography alone, and in combination in the detection of axillary metastases were 82%, 79%, and 85% respectively. CONCLUSION: There were no significant differences between PET, ultrasonography, and PET in combination with ultrasonography regarding sensitivity, specificity and accuracy in the detection of axillary metastases.     

Axillary lymph node and bone marrow micrometastases of breast cancer]

Micrometastatic disease from breast cancer is a major concern both for clinicians and pathologists. Histologically, they can be defined as potentially invasive microfoci of tumoral cancer cells located in the vicinity of blood vessels and are a distinct entity from residual disease. They are mainly looked for in bone marrow and lymph nodes specimens and their diagnosis is currently easier thanks to immunohistochemistry. Provided a standard definition of micrometastatic disease and standard screening procedures can be met, the presence of micrometastases at the time of diagnosis could represent a major parameter in therapeutic decision-making. Although controversial, the presence of medullary and axillary lymph node micrometastases appears to be a major prognostic factor in terms of survival. Recognition of this entity could help in better defining the high-risk subset of patients who would potentially benefit from adjuvant chemotherapy.     

Beyond lymph node staging: molecular predictors of outcome in breast cancer

This article briefly reviews the exciting, yet unproven, reports of alternate methods of predicting outcomes in breast cancer and highlights new molecular methods of diagnosing, classifying, and treating this disease. The author starts by reviewing well-known factors in breast cancer with which all alternate methods of staging and predicting outcomes must be compared prospectively.     

Fluorodeoxyglucose-positron emission tomography and sentinel lymph node biopsy in staging primary cutaneous melanoma.

AIM: We report the value of sentinel lymph node (SLN) biopsy and fluorodeoxyglucose-positron emission tomography (FDG-PET) in relation to SLN biopsy in staging primary cutaneous melanoma. METHODS: Fifty-five patients with primary cutaneous melanoma >1.0 mm. Breslow thickness and no palpable regional lymph nodes underwent a FDG-PET scan before SLN biopsy. RESULTS: SLN's were retrieved in 53 patients. Melanoma metastases were found in the SLN of 13 patients. FDG-PET detected the lymph node metastases in two of the 13 patients with SLN metastases. In five patients FDG accumulation was recorded in a regional lymph node basin, while no tumour positive SLN was found. In eight patients FDG-PET showed increased activity at a site of possible distant metastasis. Metastatic disease was confirmed in one patient. No explanation for the positive FDG-PET result could be found in five cases. CONCLUSION: FDG-PET should not be considered in this group. SLN biopsy reveals regional metastases that are too small to be detected by FDG-PET. The prevalence of distant metastases is too small to justify routine use of FDG-PET.     

Axillary lymph node metastasis in lung cancer

Study objectives Axillary lymph node metastasis (ALNM) from lung cancer is rare. Its prognosis and effective treatments remain unknown. To evaluate clinicopatholgical characteristics of such lung cancer patients, we performed a retrospective study of them, who had ALNM at the time of initial presentation or developed ALNM in their clinical courses. Methods We reviewed the medical records and pathological reports of all patients at our division who had a diagnosis of primary lung cancer from January 1985 through August 2007. Results Ten (0.75%) of 1,340 patients had ALNM. In eight of them, ALNM was detected at the time of initial diagnosis, and two patients developed ALNM in their clinical courses. Lymphatic metastasis to mediastinum was evident in all patients. Supraclavicular and cervical lymph nodes were involved in five and three patients, respectively. One patient had direct chest wall invasion from the lung. Three patients had distant metastases other than axillary or cervical lymph nodes. Four patients received systemic chemotherapy, and another four patients received palliative chest irradiation or supportive care because of their poor performance status. Median survival time of 8 patients who were diagnosed as having ALNMs at initial presentation was 7 months. Conclusions The most likely mechanism for axillary node involvement is intercostal lymphatics via spread from mediastinal lymph node metastasis. Routine palpation of the axillae is recommended if chest wall invasion, mediastinal and/or supraclavicular lymph nodes are found either at initial presentation or at follow-up of patients.     

前哨淋巴结活检术及正电子发射体层显像诊断乳腺癌腋窝淋巴结状态的研究进展

前哨淋巴结活检术 (sentinellymphnodebiopsy ,SLNB)是 2 0世纪 90年代提出的乳腺癌腋窝手术的新观念 ,可准确地预测腋窝淋巴结的转移状况。正电子发射体层显像 (positronemissiontomography ,PET)作为最新的影像学技术 ,在肿瘤诊断、指导治疗方面有重要价值。综述了两者诊断腋窝淋巴结转移的原理、应用、影响因素及联合应用的临床意义。     

Mediastinal lymph node staging by means of positron emission tomography is less sensitive in elderly patients with non-small-cell lung cancer

PURPOSE: We sought to identify the impact of age on the sensitivity and specificity of integrated positron emission tomography/computed tomography (PET-CT; CT) on mediastinal lymph node staging of patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: We conducted a retrospective review of 206 consecutive patients with histologically proven NSCLC who underwent resection and/or mediastinoscopy in our center between September 2004 and January 2007. All of these patients had preoperative staging with integrated PET-CT as an adjunct to chest CT before resection and/or mediastinoscopy. Diabetic patients and patients who received neoadjuvant chemotherapy were excluded. The pathologic results of all of these cases were reviewed and correlated with those on CT and integrated PET-CT. RESULTS: The sensitivity and positive predictive values (PPV) of PET-CT in mediastinal nodal staging were significantly lower in elderly patients (age>or=65 years; sensitivity, 42%; PPV, 66%) than in younger patients (age<65 years; sensitivity, 52%; PPV, 74%). Specificity and negative predictive values were similar in both groups. CONCLUSION: PET-CT staging of the mediastinum is less sensitive in elderly patients with NSCLC who have a lower PPV. Positive mediastinal uptake on PET-CT should be verified by mediastinoscopy, irrespective of age. Elderly patients with positive mediastinal uptake should not be refuted a curative intent surgical resection on the basis of positive mediastinal uptake alone.     

Axillary lymph node dissection in breast cancer--current status and controversies, alternative strategies and future perspectives

Axillary lymph node dissection (ALND) has traditionally been considered as a standard procedure in the surgical management of patients with breast cancer. The goals of ALND in breast cancer surgery are: (a) to provide accurate prognostic information, (b) to maintain local control of the disease in the axilla and (c) to provide a rational basis for decisions about adjuvant therapy. Although controversial, ALND may also be associated with a small therapeutic benefit. Recently, the question of whether ALND is needed for every patient with invasive breast cancer has been the subject of ongoing debate in the literature. This is mainly due to the widespread use of adjuvant systemic therapy for patients with node-negative breast cancer and to the increasingly frequent detection of small invasive cancers by mammographic screening; the majority of these patients have negative axillae. Sentinel lymph node (SLN) biopsy is a new, promising, minimally invasive procedure, which accurately predicts nodal status with minimal morbidity, and reserves ALND for patients with positive SLN biopsies. However, this method is still investigational. Partial (levels I and II) ALND remains the gold standard in the surgical management of patients with breast cancer.     

Role of positron emission tomography in pretreatment lymph node staging of uterine cervical cancer: a prospective surgicopathologic correlation study

We evaluated the accuracy of FDG-PET in diagnosing metastatic para-aortic and pelvic lymph nodes in patients with cervical cancer by comparing this noninvasive imaging technique with surgicopathologic results. We performed FDG-PET in 54 patients with cervical cancer at FIGO stages IB-IVA who were about to undergo lymphadenectomy. For region-specific comparisons, we divided the nodes into eight regions (four on each side: para-aortic, common iliac, external iliac, and internal iliac/obturator). Histological examination revealed metastases in 15 (28%) of the patients, with region-specific analysis identifying 37 (8.6%) metastases in 432 regions. The region-specific findings of FDG-PET exhibited a sensitivity of 38% and a positive predictive value (PPV) of 56%. The sensitivity increased to 52% and 65% when we restricted the pathologic criterion for metastases to tumour-invasion diameters of >5 and >10 mm, respectively. These results indicate that FDG-PET exhibited low sensitivity and PPV (especially for microscopic metastases) and hence cannot replace surgical staging, although it might still be useful for detecting metastases in patients with clinical conditions that make surgical staging inappropriate.