CT lymphography for sentinel lymph node mapping of clinically N0 early oral cancer.

BACKGROUND: The objectives of this retrospective study were to evaluate the usefulness of computed tomography lymphography (CTL) and to clarify the optimal timing of CTL in sentinel lymph node (SLN) mapping of clinically N0 early oral cancer. METHODS: Twenty patients with clinically N0 early oral cancer underwent CTL with a 128 multi-detector row CT scanner to detect SLN the day before resection of primary tumor and SLN biopsy with indocyanine green (ICG) fluorescence guidance. CT scanning was performed in the first 10 patients at 2, 5, and 10 min after submucosal injection of iopamidol and in the remaining 10 patients at 2, 3.5, 5, and 10 min after the injection of contrast medium. We evaluated the SLN detection rate at each scan timing and the number and location of SLNs. We evaluated whether CTL-enhanced SLNs could be identified intraoperatively as ICG fluorescent lymph nodes. RESULTS: SLNs were detected by CTL in 19 of the 20 patients (95.0%), and the mean number of SLNs was 2 (range, 1-4). All SLNs were located on the ipsilateral side; 35 of 37 SLNs were located at level I and II, and 2 SLNs were lingual lymph nodes. All SLNs could be detected 2 min and 3.5-5 min after contrast medium injection, and CTL-enhanced SLNs could be identified intraoperatively as fluorescent lymph nodes. CONCLUSIONS: CTL could facilitate the detection of SLNs in early oral cancer, and the optimal timing of CT scanning was at 2 and 5 min after injection of contrast medium.

Delineation of Neck Clinical Target Volume Specific to Nasopharyngeal Carcinoma Based on Lymph Node Distribution and the International Consensus Guidelines.

PURPOSE: To establish the regional lymph node (LN) distribution probability map and draw the neck clinical target volume specific to nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: One thousand patients with pathologically proven NPC were enrolled from January 2010 to December 2011. The center point of the LNs with a minimal axial diameter of ≥4 mm was marked on a single treatment planning computed tomography scan. The neck LN levels I to X using the 2013 updated international consensus guidelines were also contoured. LN distribution probability maps and distribution curves were established. The relationships between the LN distribution and consensus guidelines were analyzed to propose modifications for clinical target volume boundaries specific to NPC. RESULTS: A total of 10,651 LNs from 959 patients were marked. Based on the distribution of LNs and consensus guidelines, most of the LN levels defined in the 2013 updated consensus guidelines were confirmed to be comprehensive and applicable for NPC. However, for level Vb, 13.3% of cases (11 of 83) had LNs beyond the posteromedial border. For level VIIa (retropharyngeal LN), 1.5% of cases (12 of 819) had LNs above the cranial boundary, and 5 cases had LNs that emerged in the medial group. Moreover, we confirmed that no LN had been detected in certain areas of levels Ib, II, IVa, and Vc. Accordingly, a new level VIIc was proposed to include the medial group of retropharyngeal LNs, moderately extended boundaries for levels Vb and VIIa were recommended, and reduced boundaries are possibly adaptable for levels Ib, II, IV, and Vc. CONCLUSIONS: Most LN levels in the 2013 updated consensus guidelines are comprehensive and applicable for NPC. We have proposed a new level VIIc to include a medial group of retropharyngeal LNs, recommended moderate extended boundaries for levels Vb and VIIa, and suggested that the boundaries for levels Ib, II, IV, and Vc might be reduced.

A Validation Study of Near-Infrared Fluorescence Imaging of Lymphatic Vessels in Humans.

BACKGROUND: Near-infrared fluorescence (NIRF) imaging is a new imaging technique that is used to visualize lymphatic vessels in humans. It has a high spatial and temporal resolution, allowing real-time visualization of lymphatic flow. METHODS AND RESULTS: The current study investigated the intra- and inter-individual variability of the technique, and how local hypo- and hyperthermia (20°C, 40°C), as well as exercise affect lymph transport. In this study, 10 healthy volunteers were studied twice, with 2 weeks between. NIRF imaging was conducted by using intradermal Indocyanine green injections and a custom-built camera setup. All data were blinded before analysis and presented as mean ± standard deviation. Mean contraction frequency and lymph propulsion velocity were 0.59 ± 0.13 minutes-1 and 1.51 ± 0.24 cm/s, respectively, with no significant difference during each 4 hours examination or between the two visits. The maximal pressure that the lymphatic flow in the vessels could overcome on test day 1 and 2 was 56 ± 9 mmHg and 57 ± 9 mmHg, respectively (p = 0.496). Local hyperthermia increased contraction frequency from 0.62 ± 0.4 minutes to 1.46 ± 0.5 minutes-1 (p < 0.05). Hypothermia caused no significant changes. Immediately after exercise (exercising at a simulated distance of 1.4 km on a cycle ergometer), an increase in lymph propulsion velocity from 1.5 ± 0.49 to 2.2 ± 0.63 cm/s was observed (p < 0.05); whereas contraction frequency was unaltered. A decrease in contraction frequency from 0.68 ± 0.25 minutes to 0.35 ± 0.19 minutes-1 was observed 10 minutes after exercise, without a change in velocity. CONCLUSIONS: NIRF imaging can be conducted for 4 hours without a change in lymphatic activity. Furthermore, it has the sensitivity to detect changes in lymphatic activity by local hyperthermia and exercise. No changes were seen after local hypothermia. Pumping pressure shows good repeatability, whereas the other parameters show poor repeatability.

Análisis de los factores relacionados con la sobreestadificación y la positividad del ganglio centinela en las pacientes con diagnóstico inicial de carcinoma ductal in situ / Analysis of factors related to upstaging and sentinel node positivity in the initial diagnosis of ductal carcinoma in situ

Objetivo. Determinar el porcentaje de pacientes con diagnóstico inicial de carcinoma ductal in situ (CDIS) que presentó infiltración tras la excisión quirúrgica e identificar los factores relacionados tanto con la sobreestadificación como con la positividad del ganglio centinela (GC) en el estudio definitivo. Material y métodos. Análisis retrospectivo de 135 pacientes diagnosticadas mediante biopsia core de CDIS a las que se les realizó biopsia selectiva del GC de forma consecutiva de 2003 a 2011. La técnica fue mixta en el período inicial y posteriormente mediante administración intraperilesional de radiocoloides. En 2009 se introdujo una gammacámara portátil y se inició el estudio intraoperatorio molecular mediante amplificación de ácido nucleico de un solo paso. Resultados. Se produjo sobreestadificación en 45 de las 135 pacientes (33,3%), de las que 30 (22,2%) presentaron CDIS con microinfiltración y 15 (11,1%) carcinoma infiltrante. Los CDIS con microinfiltración mostraron mayor tamaño, mayor porcentaje de alto grado, de HER2 positivo y de Ki-67 alto que los CDIS (p < 0,001, p < 0,001, p = 0,002 y p = 0,031, respectivamente). Los porcentajes de positividad del GC fueron del 3,6% en el CDIS, del 6,9% en el CDIS con microinfiltración y del 20% en los carcinomas infiltrantes, correspondiendo a 8 pacientes, de las cuales 6 presentaron HER2 positivo y Ki-67 alto. Conclusiones. El porcentaje global de infraestimación fue alto, principalmente debido a la presencia de microinfiltración. Tanto esta como la afectación metastásica del GC mostró relación con el HER2 positivo y el Ki-67 alto, por tanto, disponer de estos datos en la biopsia percutánea podría ser relevante para establecer la indicación de realización de biopsia selectiva del GC en el CDIS

Objective. To determine the percentage of patients with ductal carcinoma in situ (DCIS) with infiltration after surgical excision and to identify the factors related to both upstaging and sentinel node (SN) positivity in the final study. Material and methods. A retrospective analysis was performed in 135 patients diagnosed with DCIS by core biopsy who subsequently underwent sentinel lymph node biopsy from 2003 to 2011. In the first period of the study, the technique was mixed and subsequently consisted of intra-perilesional radiocolloid administration. In 2009, a portable gamma camera was introduced and we began to use intraoperative one-step nucleic acid amplification. Results. Upstaging occurred in 45 of the 135 patients (33.3%), of which 30 (22.2%) had DCIS with microinfiltration and 15 (11.1%) had invasive carcinoma. Compared with DCIS, DCIS with microinfiltration were larger and showed a higher percentage of high grade, HER2 positivity and high Ki-67 (P < .001, P < .001, P = .002 and P = .031, respectively). SN positivity rates were 3.6% in DCIS, 6.9% in DCIS with microinfiltration, and 20% in invasive carcinomas, corresponding to 8 patients, of whom 6 showed HER2-positivity and high Ki-67. Conclusions. Overall underestimation was high, mainly due to the presence of microinfiltration. Both microinfiltration and metastatic SN involvement were associated with HER2-positivity and high Ki-67. Therefore, the availability of this information in core needle biopsy could be relevant in establishing the indication for sentinel lymph node biopsy in DCIS

Are Radiation Therapy Oncology Group Para-aortic Contouring Guidelines for Pancreatic Neoplasm applicable to other malignancies--assessment of nodal distribution in gynecological malignancies.

PURPOSE: Intensity modulated radiation therapy is used to reduce dose to adjacent critical structures while maintaining adequate target coverage, but it requires precise target localization. We report the 3-dimensional distribution of para-aortic (PA) lymph nodes (LN) in pelvic malignancies. We propose a guideline to accurately define the PA LN by anatomic landmarks and compare our data with published guidelines for pancreatic cancer. METHODS AND MATERIALS: A retrospective analysis was performed on 46 patients with pelvic malignancies and positive PA LNs. Positive LNs were defined based on size and morphology or fluorodeoxyglucose avidity. All PA LNs were characterized into 3 groups based on location: left PA (between aorta and left psoas muscle), aortocaval (between aorta and inferior vena cava), and right paracaval (between inferior vena cava and right psoas muscle). Patients with retrocrural LNs were also analyzed. RESULTS: One hundred thirty-three positive PA LNs were evaluated. The majority of the PA LNs were in the left PA (59%) and aortocaval (35) regions, and only 8% were in the right paracaval region. All patients with positive right paracaval LNs also had involved left PA LNs, with only 1 exception. The highest PA LN involvement was at the level of the renal vessels and was seen in 28% of patients. Of these patients with disease extending to renal vessels, 38% had retrocrural LN involvement. CONCLUSIONS: The nodal contouring for the PA region should not be defined by a fixed circumferential margin around the vessels. The left PA and aortocaval spaces should be covered adequately because these are common locations of PA LNs. For microscopic disease superiorly, contouring should extend up to renal vessels rather than a fixed bony landmark. For patients who have nodal involvement at renal vessels, one can consider including retrocrural LNs. Radiation Therapy Oncology Group Para-aortic Contouring Guidelines for Pancreatic Neoplasm are not applicable to gynecological malignancies.

Summary ROC curve based on a weighted Youden index for selecting an optimal cutpoint in meta-analysis of diagnostic accuracy.

Established approaches for analyzing meta-analyses of diagnostic accuracy model the bivariate distribution of the observed pairs of specificity Sp and sensitivity Se, thus accounting for across-study correlation. However, it is still a matter of debate how to define a summary ROC (SROC) curve. It was recently pointed out that the SROC curve is in principle unidentifiable if only one (Sp, Se) pair per study is known. We evaluate an alternative approach, modeling the study-specific ROC curves based on the assumption of linearity in logit space. A setting is considered in which the pair (Sp, Se) that is selected for publication in a particular study maximizes a weighted Youden index λSe+(1-λ)Sp with a given weight λ.This leads to a fixed slope (1-λ)/λ of the ROC curve in (1-Sp, Se), equivalent to a slope of (1-λ)Sp(1-Sp)/(λSe(1-Se)) for the corresponding straight line in logit space. While the slope depends on the variance ratio of the underlying distributions, the intercept is a function of the mean difference. Our approach leads in a natural way to a new, model-based proposal for a summary ROC curve. It is illustrated using an example from the literature.

RECIST and WHO criteria evaluation of cervical, thoracic and abdominal lymph nodes in patients with malignant lymphoma: manual versus semi-automated measurement on standard MDCT slices.

PURPOSE: Since semi-automated lesion quantification may be more precise than manual uni- and bidimensional measurements, the purpose of this study was to compare semi-automated with manual evaluations of cervical, thoracic and abdominal lymph nodes in patients with malignant lymphoma. MATERIALS AND METHODS: 62 patients with known malignant lymphoma underwent staging with contrast-enhanced 16-MDCT (16x0.7 mm coll., 120 kV, cervical/thoracic/abdominal: 150/120/160 mAseff., 1/1.25 /1 pitch, 4/3 - 5/4 - 5/4 slice thickness/reconstruction increment). On the basis of these standard reconstructed slices, each lesion was quantified in terms of RECIST and its longest orthographic diameter using a semi-automated software tool (Syngo CT Oncology, Siemens Medical Solutions, Forchheim, Germany) and manually by an experienced radiologist. The degree of agreement between manual measurements and software quantification was statistically assessed by computing the concordance correlation coefficient kappa and represented graphically in corresponding Bland-Altman plots. RESULTS: 74/80 cervical, 51/80 thoracic and 75/80 abdominal lymph nodes were correctly evaluated by the software. A strong degree of agreement between both measurement techniques (RECIST diameter: kappa = 0.97 (cervical)/0.98 (thoracic)/0.99 (abdominal); longest orthographic diameter: kappa = 0.97/0.93/0.97) was obtained. CONCLUSION: Semi-automated measurement of cervical, thoracic and abdominal lymph nodes showed valid results on standard axial reconstructions compared to manual quantification with the limitation of a high false segmentation rate in thoracic lymph nodes.

A unification of models for meta-analysis of diagnostic accuracy studies.

Studies of diagnostic accuracy require more sophisticated methods for their meta-analysis than studies of therapeutic interventions. A number of different, and apparently divergent, methods for meta-analysis of diagnostic studies have been proposed, including two alternative approaches that are statistically rigorous and allow for between-study variability: the hierarchical summary receiver operating characteristic (ROC) model (Rutter and Gatsonis, 2001) and bivariate random-effects meta-analysis (van Houwelingen and others, 1993), (van Houwelingen and others, 2002), (Reitsma and others, 2005). We show that these two models are very closely related, and define the circumstances in which they are identical. We discuss the different forms of summary model output suggested by the two approaches, including summary ROC curves, summary points, confidence regions, and prediction regions.

Utility of lymphangiography in the prediction of lymph node metastases in patients with cervical cancer.

Our objective was to assess the value of lymphangiography in selecting patients for surgical staging of locally advanced cervical cancer. We reviewed our computerized database to identify patients with cervical cancer who had abnormal findings on lymphangiography and underwent retroperitoneal lymph node dissection between September 1991 and January 1996. The records of these patients were retrospectively reviewed, and the following data were retrieved: clinical tumor stage and findings on lymphangiography at surgery, and on pathologic examination of resected lymph nodes. The lymphangiograms were reviewed and reinterpreted in blinded fashion by two of the authors. The positive and negative predictive values of lymphangiography for the presence of lymph node metastases were calculated, with findings on pathologic examination of lymph nodes used as the gold standard. The positive and negative predictive values of surgeons' clinical assessments at surgery were also calculated. Fifty patients met the selection criteria and constituted the study population. Fourteen patients (28%) had histologically negative nodes, and 36 patients (72%) had lymph node metastases. Thirty-three patients had metastases to pelvic nodes, 1515 patients had metastases to common iliac nodes, and 1616 patients had metastases to para-aortic nodes. The positive predictive value of lymphangiography for lymph node metastases was 74% for pelvic nodes, 73% for common iliac nodes, and 88% for para-aortic nodes. The negative predictive value of lymphangiography for lymph node metastasis was 76% for common iliac nodes and 77% for para-aortic nodes. Overall, 46% of the patients selected for surgical exploration had histologic findings of either common iliac or para-aortic lymph node metastases; these findings led clinicians to extend radiation fields to cover the para-aortic lymph nodes. Lymphangiography is helpful in selecting patients with cervical cancer who have a high risk of common iliac or para-aortic lymph node metastasis. However, more accurate and more readily available noninvasive methods of evaluating cervical patients for the presence of regional disease continue to be needed.

Properties of the summary receiver operating characteristic (SROC) curve for diagnostic test data.

The summary receiver operating characteristic (SROC) curve has been recommended to represent the performance of a diagnostic test, based on data from a meta-analysis. However, little is known about the basic properties of the SROC curve or its estimate. In this paper, the position of the SROC curve is characterized in terms of the overall diagnostic odds ratio and the magnitude of inter-study heterogeneity in the odds ratio. The area under the curve (AUC) and an index Q(*) are discussed as potentially useful summaries of the curve. It is shown that AUC is maximized when the study odds ratios are homogeneous, and that it is quite robust to heterogeneity. An upper bound is derived for AUC based on an exact analytic expression for the homogeneous situation, and a lower bound based on the limit case Q(*), defined by the point where sensitivity equals specificity: Q(*) is invariant to heterogeneity. The standard error of AUC is derived for homogeneous studies, and shown to be a reasonable approximation with heterogeneous studies. The expressions for AUC and its standard error are easily computed in the homogeneous case, and avoid the need for numerical integration in the more general case. SE(AUC) and SE(Q(*)) are found to be numerically close, with SE(Q(*)) being larger if the odds ratio is very large. The methods are illustrated using data for the Pap smear screening test for cervical cancer, and for three tests for the diagnosis of metastases in cervical cancer patients.

Is it wise to eliminate lymphography from the staging of Hodgkin's disease?

We believe that lymphography and CT are complementary rather than mutually exclusive techniques for the diagnosis and staging of HD. Unfortunately, it seems that many radiologists and clinicians disregard the ability of lymphography to provide qualitative information on lymph node architecture, which is not available by CT. The use of lymphography is declining in several teaching centers throughout the world. This makes it difficult for young radiologists to acquire the skills needed to perform and interpret lymphographies successfully. In turn, radiologists who have little experience with lymphography are less likely to use the technique. Because most of the treatment-related morbidity in HD is dose-related, and because lymphography helps to avoid over- and undertreatment, we believe that high-quality lymphography continues to have a significant role in the staging of selected HD patients. Moreover. lymphography may reduce both the cost of management and the morbidity rate in many HD patients. One solution would be to continue to use lymphography in a small number of institutions specialized in the management of HD.

Learning curves and breast cancer lymphatic mapping: institutional volume index.

INTRODUCTION: To date, studies of breast cancer lymphatic mapping (LM) have analyzed success with respect to individual surgeons. However, LM and sentinel lymph node biopsy (SLNBx) are procedures that require institutional multidisciplinary cooperation between the departments of radiology, pathology, and surgery. Thus, it is important to evaluate these procedures with respect to the institution. This study examines 30 institutions to clarify the value of the institutional volume index (IVI) (cases/month) to the outcome of LM and SLNBx in breast cancer. METHODS: From July 1997 to July 1999, 30 institutions participated in the Department of Defense national breast LM trial. All participants underwent a 2-day training course for surgeons, nuclear medicine physicians, and pathologists. The records for each institution were prospectively accrued and submitted to a database. The false negatives, failure rates, and IVI were calculated for each institution. A logistic regression model plots the relationship between IVI and institutional failure rate. Using a multivariate analysis, mapping failure was analyzed as a function of case number with respect to the individual surgeon and the institution as a whole. RESULTS: False negative results were demonstrated in only 5 (4%) cases among all institutions and were excluded from further analysis due to small numbers. Mapping failures were found in all but 7 of the 30 institutions whose data were complete. There were 71 mapping failures among 74 surgeons over 555 cases, which yielded an overall failure rate of 12.79% (71 555). The logistic regression model revealed an inverse relationship between IVI and institutional failure rate. However, the multivariate analysis revealed that the individual surgeon performance was the most significant factor in determining institutional mapping success. CONCLUSION: Failure to map can be a function of multiple factors including surgical skill, surgical volume index, and injection method of the SLN patient, all under the quality control of an institution. The surgical failure rate on the other hand is a function of surgical skill, surgical volume, and injection methods. While differences in mapping success exist across institutions, this disparity is not due to factors associated with the institution as a whole, but lie with the individual surgeon.

Radiographic detail and variation of the nominal focal spot size: the "focal effect".

It is not generally appreciated that there is a gradation of the focal spot size from the anode to cathode end of an x-ray field that can dramatically affect radiographic detail from one end of a radiograph to the other. The authors name this gradation the "focal effect." Gradations in radiation intensity and focal spot size were measured from anode end to cathode end of a 14 x 17-inch field and were visually demonstrated with lymphangiograms and line-pair patterns. The degradation in spatial resolution along the anode-cathode axis was found to be as much as 75%, depending on the orientation of the patient with respect to the x-ray tube. Radiographic detail is, therefore, significantly improved (even when the large focal spot is used) by exploiting the focal effect and placing the body part requiring the best radiographic detail at the anode end of the table.

[Standardization of diagnostic studies in thyroid diseases]. / Standartizatsiia diagnosticheskogo issledovaniia pri zabolevaniiakh shchitovidnoi zhelezy.

Standardized diagnosis of thyroid diseases includes 3 levels of diagnostic investigation proper based on the syndromic approach and distributed by 3 levels of providing medical care to population. At the 1st level of primary health care the use of "active" detectability ensures timely detection of symptomless thyroid cancer at early stages and early detection of the syndrome of its disturbance and makes it possible to start the prevention of functional and organic changes. At the second level of providing specialized medical care the role of adjuvant diagnostic methods acquires more importance (ultrasound investigations, radioimmunoassay, diagnostic puncture, thyroid lymphography) which are characterized by minimum dose formation, sufficient simplicity, reliability, low cost, a possibility to be widely employed in clinical practice, and safety. The 3rd level (scanning, endoscopy, angiography, CT, NMR) depends on the availability of expensive equipment employed in specialized clinical and diagnostic centers. The proposed algorithms of investigation can be changed in case of the appearance of new more informative and efficient diagnostic methods.

[Accuracy and general relevance of preoperative lymphography in gynaecology (author's transl)]. / Treffsicherheit und Stellenwert der präoperativen Lymphographie in der Gynäkologie.

Lymphographic findings obtained from 304 patients were compared with results obtained from histological testing of extirpated lymph nodes, with the view to making an assessment of accuracy of presurgical lymphography. Agreement was recordable in 82.3 per cent of all cases, while 3.3 per cent of the findings were falsely negative and 4.9 per cent falsely positive. The relevance of preoperative lymphography to diagnosis and planning of therapy for various gynaecological carcinomas is discussed.

[Lymphographic pattern in lymphogranulomatosis -- a study on the prognostic value and relation to histology (author's transl)]. / Lymphographisches Bild bei Lymphogranulomatose -- Eine Studie über die prognostische Aussagekraft und die Beziehung zur Histologie.

The possibilities offered by lymphography with regard to supplying clear information in respect of prognosis and histology in patients with lymphogranulomatosis, were analysed in 83 patients via retrospective evaluation of clinical data and x-ray findings, using a computer. Disclosure of pathological lymphangiographic changes signifies poor prognosis not requiring further differentiation. Analysis of the pathological storage patterns appears to indicate that these are images of an infiltrative process proceeding in three stages. Solitary filling defects appear first, followed by a lucunar image and, finally, a cystic storage pattern. No different prognostic conclusions can be drawn from the individual stages. No correlation was found between lymphographic storage patterns and histological findings.

[Accuracy of lymphography in carcinoma of the cervix (author's transl)]. / Zur Treffsicherheit der Lymphographie beim Zervixkarzinom.

A review has been made of lymphographic diagnoses recorded from patients with cervical carcinoma over more than five years. The diagnosis by lymphography of nodes metastases had to be altered in some 25 per cent, and correction proved necessary also in cases in which lymphography had failed to yield conclusive information. - In the group with lymphographically secured cancer lymph nodes coincided with histological results in 70 per cent of all primary and 90 per cent of secondary checks. Comparable gaps were recorded also from the group with lymphographically inconclusive information on lymph node cancer. - The following conclusions are drawn from the study described: (a) The accuracy of lymphographic diagnosis depends on the experiences of the examiner and changes within time and this must be considered in the evaluation of therapeutic success or failure. - (b) Conclusive findings in the context of lymph node problems are obtainable from selective use of lymphography.