Positron emission tomography (PET) was used to quantify 18fluorodeoxyglucose (18FDG) uptake in rabbits with experimental pneumonitis localized to the right upper lobe. In Streptococcus pneumoniae-induced pneumonia, which causes a profound inflammatory response lasting several days before it resolves, 18FDG uptake was pronounced at 15 h after the onset of inflammation, but by 48 h there was little uptake. In bleomycin injury, which progresses from an acute inflammatory stage to chronic inflammation and scarring, 18FDG uptake detectable by PET persisted for up to 21 d. Autoradiography of histologic sections after intravenous administration of [3H]deoxyglucose 15 h after streptococcal instillation and 2 wk after bleomycin instillation showed that, in both models, deoxyglucose uptake was localized to neutrophils. In the streptococcal model there was little 18FGD signal at 6 h, when major neutrophil migration occurs. At 15 h, [3H]deoxyglucose-labeled neutrophils were present in the airspaces but not in the alveolar septa, suggesting that the deoxyglucose signal reflected a postmigratory neutrophil event, probably the respiratory burst. Thus, PET of 18FDG uptake may provide a novel and readily repeatable, noninvasive approach to the in vivo study of neutrophil activity at otherwise inaccessible sites.
A retrospective study of 33 patients with cystosarcoma phyllodes was done. Eight of these patients had metastases, and the clinical and histologic criteria predicting the development of metastases were examined. The most reliable predictor was the presence of stromal overgrowth; this appears to be necessary for metastasis to occur. Other useful indicators of clinical behavior were the degree of mitotic activity, nuclear pleomorphism, and infiltrating margins. Based on these data and a literature review, the authors suggest close follow‐up of patients whose primary tumors contain areas of stromal overgrowth because, in all series combined, the risk of metastatic spread in such patients was 72% within 5 years. Among these high‐risk patients, local recurrence is another indication that metastasis is likely.
The role of inflammatory cells such as neutrophil granulocytes in the pathogenesis of pulmonary scarring is unclear. We determined the metabolic activity of neutrophils with positron emission tomography (PET) to measure regional uptake of (18F)-2-fluoro-2-deoxy-D-glucose (18FDG) following its intravenous injection. Fibrogenic or nonfibrogenic substances were instilled into the right upper lobe of rabbit lungs. Time course and intensity of the 18FDG signal in the affected region varied markedly, depending on the stimulus. Time to peak signal (Tmax) and rate constant for its decline (k) for the test substances were, respectively: C5a 10 h (Tmax), 0.045 +/- 0.030 h-1 (k); Streptococcus pneumoniae 15 h, 0.068 +/- 0.012 h-1; bleomycin 28 h, 0.002 +/- 0.001 h-1; microcrystalline silica (microXSiO2), 90 h, 0.0012 +/- 0.0007 h-1; amorphous silica (aSiO2), no response. Response to the nonfibrogenic agents C5a, S. pneumoniae and aSiO2 was brief or nonexistent, falling to baseline values within 3 d, whereas that to the fibrogenic agents bleomycin and microXSiO2 persisted for up to 4 wk. Neutrophil numbers in the lung were proportional to the 18FDG signal following C5a and S. pneumoniae, but not bleomycin and microXSiO2. Autoradiography of lungs following administration of (3H)-deoxyglucose [(3H)-DG] showed specific localization to neutrophils in all models. Thus, 18FDG uptake provides a remarkably specific measure of neutrophil activity in situ, and the development of pulmonary fibrosis may be related to persistence of this activity.
Lymph node metastasis informs prognosis and is a key factor in deciding further management, particularly adjuvant chemotherapy. It is core to all contemporary staging systems, including the widely used tumor node metastasis staging system. Patients with node-negative disease have 5-year survival rates of 70%-80%, implying a significant minority of patients with occult lymph node metastases will succumb to disease recurrence. Enhanced staging techniques may help to identify this subset of patients, who might benefit from further treatment. Obtaining adequate numbers of lymph nodes is essential for accurate staging. Lymph node yields are affected by numerous factors, many inherent to the patient and the tumour, but others related to surgical and histopathological practice. Good lymph node recovery relies on close collaboration between surgeon and pathologist. The optimal extent of surgical resection remains a subject of debate. Extended lymphadenectomy, extra-mesenteric lymph node dissection, high arterial ligation and complete mesocolic excision are amongst the surgical techniques with plausible oncological bases, but which are not supported by the highest levels of evidence. With further development and refinement, intra-operative lymphatic mapping and sentinel lymph node biopsy may provide a guide to the optimum extent of lymphadenectomy, but in its present form, it is beset by false negatives, skip lesions and failures to identify a sentinel node. Once resected, histopathological assessment of the surgical specimen can be improved by thorough dissection techniques, step-sectioning of tissue blocks and immunohistochemistry. More recently, molecular methods have been employed. In this review, we consider the numerous factors that affect lymph node yields, including the impact of the surgical and histopathological techniques. Potential future strategies, including the use of evolving technologies, are also discussed.
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