Implications of intraglandular lymph node metastases in primary carcinomas of the parotid gland

OBJECTIVES/HYPOTHESIS Assess the diagnostic and prognostic relevance of intraglandular lymph node (IGLN) metastases in primary parotid gland carcinomas (PGCs). STUDY DESIGN Retrospective study at a tertiary referral university hospital. METHODS We reviewed the records of 95 patients with primary PGCs, treated at least surgically, between 1997 and 2010. We assessed the clinicopathological associations of IGLN metastases, their prognostic significance, and predictive value in the diagnosis of occult neck lymph node metastases RESULTS Twenty-four (25.26%) patients had IGLN metastases. This feature was significantly more prevalent in patients with advanced pT status (P = .01), pN status (P < .01), and overall stage (P < .001); high-risk carcinomas (P = .01); as well as in patients with treatment failures (P < .01). IGLN involvement was significantly associated with decreased univariate disease-free survival (P < .001). Positive and negative predictive values and accuracy for IGLN involvement in the detection of occult neck lymph node metastases were 63.64%, 90.48%, and 84.91%, respectively. The diagnostic values were generally higher in patients with low-risk subtype of PGCs. CONCLUSIONS IGLN involvement provides prognostic information and is associated with advanced tumoral stage and higher risk of recurrence. This feature could be used as a potential readout to determine whether a neck dissection in clinically negative neck lymph nodes is needed or not. LEVEL OF EVIDENCE 4.

An Insight Into Cervical Cancer Screening and Treatment Capacity in Sub Saharan Africa.

OBJECTIVE Approximately 85% of cervical cancer cases and deaths occur in resource-constrained countries where best practices for prevention, particularly for women with HIV infection, still need to be developed. The aim of this study was to assess cervical cancer prevention capacity in select HIV clinics located in resource-constrained countries. MATERIALS AND METHODS A cross-sectional survey of sub-Saharan African sites of 4 National Institutes of Health-funded HIV/AIDS networks was conducted. Sites were surveyed on the availability of cervical cancer screening and treatment among women with HIV infection and without HIV infection. Descriptive statistics and χ or Fisher exact test were used as appropriate. RESULTS Fifty-one (65%) of 78 sites responded. Access to cervical cancer screening was reported by 49 sites (96%). Of these sites, 39 (80%) performed screening on-site. Central African sites were less likely to have screening on-site (p = .02) versus other areas. Visual inspection with acetic acid and Pap testing were the most commonly available on-site screening methods at 31 (79%) and 26 (67%) sites, respectively. High-risk HPV testing was available at 29% of sites with visual inspection with acetic acid and 50% of sites with Pap testing. Cryotherapy and radical hysterectomy were the most commonly available on-site treatment methods for premalignant and malignant lesions at 29 (74%) and 18 (46%) sites, respectively. CONCLUSIONS Despite limited resources, most sites surveyed had the capacity to perform cervical cancer screening and treatment. The existing infrastructure of HIV clinical and research sites may provide the ideal framework for scale-up of cervical cancer prevention in resource-constrained countries with a high burden of cervical dysplasia.

Trends in Treatment Patterns and Outcomes for Ductal Carcinoma In Situ

BACKGROUND Impact of contemporary treatment of pre-invasive breast cancer (ductal carcinoma in situ [DCIS]) on long-term outcomes remains poorly defined. We aimed to evaluate national treatment trends for DCIS and to determine their impact on disease-specific (DSS) and overall survival (OS). METHODS The Surveillance, Epidemiology, and End Results (SEER) registry was queried for patients diagnosed with DCIS from 1991 to 2010. Treatment pattern trends were analyzed using Cochran-Armitage trend test. Survival analyses were performed using inverse probability weights (IPW)-adjusted competing risk analyses for DSS and Cox proportional hazard regression for OS. All tests performed were two-sided. RESULTS One hundred twenty-one thousand and eighty DCIS patients were identified. The greatest proportion of patients was treated with lumpectomy and radiation therapy (43.0%), followed by lumpectomy alone (26.5%) and unilateral (23.8%) or bilateral mastectomy (4.5%) with significant shifts over time. The rate of sentinel lymph node biopsy increased from 9.7% to 67.1% for mastectomy and from 1.4% to 17.8% for lumpectomy. Compared with mastectomy, OS was higher for lumpectomy with radiation (hazard ratio [HR] = 0.79, 95% confidence interval [CI] = 0.76 to 0.83, P < .001) and lower for lumpectomy alone (HR = 1.17, 95% CI = 1.13 to 1.23, P < .001). IPW-adjusted ten-year DSS was highest in lumpectomy with XRT (98.9%), followed by mastectomy (98.5%), and lumpectomy alone (98.4%). CONCLUSIONS We identified substantial shifts in treatment patterns for DCIS from 1991 to 2010. When outcomes between locoregional treatment options were compared, we observed greater differences in OS than DSS, likely reflecting both a prevailing patient selection bias as well as clinically negligible differences in breast cancer outcomes between groups.

Doppler Ultrasound Flow Evaluation of the Uterine Arteries Significantly Correlates with Tumor Size in Cervical Cancer Patients.

PURPOSE The aim of this present study was to evaluate the sonographic correlation between Doppler flow characteristics of the uterine arteries and tumor size in patients with cervical cancer, in order to establish a new potential marker to monitor treatment response. METHODS This was a retrospective cohort study of 25 patients who underwent a sonographic evaluation of Doppler flow characteristics of the uterine arteries before surgery or radiochemotherapy for early and locally advanced/advanced cervical cancer, respectively, was analyzed. The primary outcome was the correlation between Doppler flow characteristics of the uterine arteries and tumor size in patients with cervical cancer. RESULTS Median age was 49 (range 26-85) years, and mean tumor size was 40.8 ± 17 mm. A significant positive correlation was found between tumor diameter and the uterine artery end-diastolic velocity (r = 0.47, p < 0.05) as well as the peak systolic velocity (r = 0.41, p < 0.05). No correlation was found between tumor size and the pulsatility index or resistance index. CONCLUSIONS In cervical cancer, uterine artery velocity parameters are associated with tumor size. This finding could become particularly useful in the follow-up of locally advanced cervical cancer patients undergoing radiochemotherapy or in corroborating the selection of women with more possibility of a high response rate during neoadjuvant chemotherapy before surgery.

Regulation of bovine IL-12R beta 2 subunit mRNA expression in bovine lymph node cells

The beta 2 subunit of the interleukin (IL)-12 receptor (IL-12R beta 2) has been shown to play an essential role in differentiation of T helper 1 (Th1) cells in the murine and human system, and antibodies raised against IL-12R beta 2 recognized this molecule on human Th1 but not Th2 cells. However, while the cytokines secreted by clones of murine cells allowed the definition of distinct T helper cell subsets, bovine clones with polarized Th1 and Th2 cytokine profiles were rarely found. This raised important questions about the regulation of immune responses in cattle. We therefore cloned bovine IL-12R beta2 (boIL-12R beta 2) DNA complementary to RNA (cDNA) from the start codon to the 3' end of the mRNA. Comparison of boIL-12R beta 2 cDNA with human and murine IL-12R beta 2 cDNA sequences revealed homologies of 85 and 78%, respectively. The deduced protein sequence showed the hallmark motifs of the cytokine receptor superfamily including the four conserved cysteine residues, the WSXWS motif and fibronectin domains in the extracellular part as well as a STAT4 binding site in the intracellular part of the molecule. Using real-time reverse transcription-polymerase chain reaction, upregulation of mRNA expression of this molecule could be demonstrated in cultured bovine lymph node cells stimulated with phytohemagglutinin. Furthermore, cells with upregulated boIL-12R beta 2 mRNA responded with enhanced expression of interferon gamma to treatment with interleukin 12.

Prognostic Implication of Lymphovascular Invasion Detected by Double Immunostaining for D2-40 and MITF1 in Primary Cutaneous Melanoma.

BACKGROUND Lymphovascular invasion (LVI) is associated with adverse outcomes in primary cutaneous melanoma (PCM). Detection of LVI by hematoxylin and eosin staining alone is 0%-6%, but targeting lymphovascular structures increases the detection rate. OBJECTIVE To examine the prognostic significance of LVI detected by immunostaining for D2-40 and microphthalmia-associated transcription factor 1 (MITF1) in PCM. METHODS The authors retrospectively analyzed 120 PCM samples. We compared the LVI detection rates of immunostaining for D2-40 only (22%), double staining for D2-40 and MITF1 (38%), and hematoxylin and eosin, and examined the association of LVI with clinicopathologic variables and clinical outcomes. RESULTS Immunolabeling with both methods significantly increased the LVI detection rate. Double staining for D2-40 and MITF1 as well as D2-40-detected LVI was significantly associated with increased Breslow thickness, number of mitoses, and sentinel lymph node (SLN) metastasis. D2-40-detected LVI was also associated with ulceration. Although the difference was not significant, double staining for D2-40 and MITF1 allowed for easier detection of LVI than D2-40 alone. LIMITATIONS This study was conducted in a tertiary referral institution; therefore, a referral bias cannot be excluded. CONCLUSIONS Immunolabeling increased detection of LVI in PCM. Because LVI is a positive predictive marker for SLN metastasis, the authors propose using anti-D2-40 and anti-MITF1 in the evaluation of LVI in patients with PCM with a certain risk of SLN metastasis.

Sentinel node mapping using hysteroscopic injection of indocyanine green and laparoscopic near-infrared fluorescence imaging in endometrial cancer staging.

Herein is presented a technique for minimally invasive sentinel node mapping. The patient had apparently early stage endometrial cancer. Sentinel node mapping was performed using a hysteroscopic injection of indocyanine green followed by laparoscopic sentinel node detection via near-infrared fluorescence. This technique ensures delineation of lymphatic drainage from the tumor area, thus achieving accurate detection of sentinel nodes.

Pelvic lymph nodes: distribution and nodal tumour burden of urothelial bladder cancer

To evaluate the number of lymph nodes and the lymph node tumour burden in different anatomical pelvic regions to better asses the impact of variations in the extent of lymphadenectomy on reported LN parameters and pelvic tumour clearance.

Tumor lymphangiogenesis and metastasis to lymph nodes induced by cancer cell expression of podoplanin

The membrane glycoprotein podoplanin is expressed by several types of human cancers and might be associated with their malignant progression. Its exact biological function and molecular targets are unclear, however. Here, we assessed the relevance of tumor cell expression of podoplanin in cancer metastasis to lymph nodes, using a human MCF7 breast carcinoma xenograft model. We found that podoplanin expression promoted tumor cell motility in vitro and, unexpectedly, increased tumor lymphangiogenesis and metastasis to regional lymph nodes in vivo, without promoting primary tumor growth. Importantly, high cancer cell expression levels of podoplanin correlated with lymph node metastasis and reduced survival times in a large cohort of 252 oral squamous cell carcinoma patients. Based on comparative transcriptional profiling of tumor xenografts, we identified endothelin-1, villin-1, and tenascin-C as potential mediators of podoplanin-induced tumor lymphangiogenesis and metastasis. These unexpected findings identify a novel mechanism of tumor lymphangiogenesis and metastasis induced by cancer cell expression of podoplanin, suggesting that reagents designed to interfere with podoplanin function might be developed as therapeutics for patients with advanced cancer.

Long-term results of International Breast Cancer Study Group Trial VIII: adjuvant chemotherapy plus goserelin compared with either therapy alone for premenopausal patients with node-negative breast cancer

The International Breast Cancer Study Group Trial VIII compared long-term efficacy of endocrine therapy (goserelin), chemotherapy [cyclophosphamide, methotrexate and fluorouracil (CMF)], and chemoendocrine therapy (CMF followed by goserelin) for pre/perimenopausal women with lymph-node-negative breast cancer.

Ultrasmall superparamagnetic particles of iron oxide allow for the detection of metastases in normal sized pelvic lymph nodes of patients with bladder and/or prostate cancer

Lymph node metastases influence prognosis and outcome in patients with bladder and prostate cancer. Cross sectional imaging criteria are limited in detecting metastases in normal sized lymph nodes. This prospective study assessed the diagnostic accuracy of ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) for the detection of metastases in normal sized lymph nodes using extended pelvic lymph node dissection (ePLND) and histopathology as the reference standard.

Molecular investigation of lymph nodes in colon cancer patients using one-step nucleic acid amplification (OSNA): a new road to better staging?

A new diagnostic system, called one-step nucleic acid amplification (OSNA), has recently been designed to detect cytokeratin 19 mRNA as a surrogate for lymph node metastases. The objective of this prospective investigation was to compare the performance of OSNA with both standard hematoxylin and eosin (H&E) analysis and intensive histopathology in the detection of colon cancer lymph node metastases.

The role of the number of uninvolved lymph nodes in predicting locoregional recurrence in breast cancer

PURPOSE: To identify groups of early breast cancer patients with substantial risk (10-year risk > 20%) for locoregional failure (LRF) who might benefit from postmastectomy radiotherapy (RT). PATIENTS AND METHODS: Prognostic factors for LRF were evaluated among 6,660 patients (2,588 node-negative patients, 4,072 node-positive patients) in International Breast Cancer Study Group Trials I to IX treated with chemotherapy and/or endocrine therapy, and observed for a median of 14 years. In total, 1,251 LRFs were detected. All patients were treated with mastectomy without RT. RESULTS: No group with 10-year LRF risk exceeding 20% was found among patients with node-negative disease. Among patients with node-positive breast cancer, increasing numbers of uninvolved nodes were significantly associated with decreased risk of LRF, even after adjustment for other prognostic factors. The highest quartile of uninvolved nodes was compared with the lowest quartile. Among premenopausal patients, LRF risk was decreased by 35% (P = .0010); among postmenopausal patients, LRF risk was decreased by 46% (P < .0001). The 10-year cumulative incidence of LRF was 20% among patients with one to three involved lymph nodes and fewer than 10 uninvolved nodes. Age younger than 40 years and vessel invasion were also associated significantly with increased risk. Among patients with node-positive disease, overall survival was significantly greater in those with higher numbers of uninvolved nodes examined (P < .0001). CONCLUSION: Patients with one to three involved nodes and a low number of uninvolved nodes, vessel invasion, or young age have an increased risk of LRF and may be candidates for a similar treatment as those with at least four lymph node metastases.

Extracapsular tumor spread and the risk of local, axillary and supraclavicular recurrence in node-positive, premenopausal patients with breast cancer

BACKGROUND: Extracapsular tumor spread (ECS) has been identified as a possible risk factor for breast cancer recurrence, but controversy exists regarding its role in decision making for regional radiotherapy. This study evaluates ECS as a predictor of local, axillary, and supraclavicular recurrence. PATIENTS AND METHODS: International Breast Cancer Study Group Trial VI accrued 1475 eligible pre- and perimenopausal women with node-positive breast cancer who were randomly assigned to receive three to nine courses of classical combination chemotherapy with cyclophosphamide, methotrexate, and fluorouracil. ECS status was determined retrospectively in 933 patients based on review of pathology reports. Cumulative incidence and hazard ratios (HRs) were estimated using methods for competing risks analysis. Adjustment factors included treatment group and baseline patient and tumor characteristics. The median follow-up was 14 years. RESULTS: In univariable analysis, ECS was significantly associated with supraclavicular recurrence (HR = 1.96; 95% confidence interval 1.23-3.13; P = 0.005). HRs for local and axillary recurrence were 1.38 (P = 0.06) and 1.81 (P = 0.11), respectively. Following adjustment for number of lymph node metastases and other baseline prognostic factors, ECS was not significantly associated with any of the three recurrence types studied. CONCLUSIONS: Our results indicate that the decision for additional regional radiotherapy should not be based solely on the presence of ECS.

The role of 3D fusion imaging in sentinel lymphadenectomy for vulvar cancer

OBJECTIVES: To evaluate the feasibility of fusion imaging compound tomography (FICT) of CT/MRI and single photon emission tomography (SPECT) versus planar scintigraphy only (plSc) in pre-surgical staging for vulvar cancer. MATERIALS AND METHODS: Analysis of consecutive patients with vulvar cancer who preoperatively underwent sentinel scintigraphy (planar and 3D-SPECT imaging) and CT or MRI. Body markers were used for exact anatomical co-registration and fusion datasets were reconstructed using SPECT and CT/MRI. The number and localisation of all intraoperatively identified and resected sentinel lymph nodes (SLN) were compared between planar and 3D fusion imaging. RESULTS: Twenty six SLN were localized on planar scintigraphy. Twelve additional SLN were identified after SPECT and CT/MRI reconstruction, all of them were confirmed intraoperatively. In seven cases where single foci were identified at plSc, fusion imaging revealed grouped individual nodes and five additional localisations were discovered at fusion imaging. In seven patients both methods identified SLN contra lateral to the primary tumor site, but only fusion imaging allowed to localise iliac SLN in four patients. All SLN predicted on fusion imaging could be localised and resected during surgery. CONCLUSIONS: Fusion imaging using SPECT and CT/MRI can detect SLN in vulvar cancer more precisely than planar imaging regarding number and anatomical localisation. FICT revealed additional information in seven out of ten cases (70%).