Metastatic Regional Lymph Nodes Research Articles

Clinical impact of 18F-FDG PET/CT on initial staging and therapy planning for breast cancer

The purpose of this study was to determine the clinical significance of 18F-FDG PET/CT on initial staging and therapy planning in patients with invasive breast cancer. One hundred and forty-one consecutive, biopsy proven preoperative and 195 postoperative high-risk breast cancer patients who were referred for PET/CT for initial staging were included in this retrospective study. The clinical stage had been determined by conventional imaging modalities prior to the PET/CT scan. Of the 141 examined preoperative patients, 19 had clinical stage I (T1N0), 51 had stage IIA (12 T2N0 and 39 T1N1), 49 had stage IIB (2 T3N0 and 47 T2N1), 12 had stage IIIA (11 T3N1, 1 T2N2), 2 had stage IIIB (2 T4N1) and 8 had stage IV. PET/CT modified the staging for 26% of stage I patients, 29% of stage IIA patients, 46% of stage IIB patients, 58% of stage IIIA patients and 100% of stage IIIB patients. PET/CT scans detected extra-axillary regional lymph nodes in 14 (9.9%) patients and distant metastasis in 41 (29%) patients. PET/CT scans detected multifocal lesions in 30 (21%) patients, multicentric lesions in 21 (14%) patients and malign foci in the contralateral breast (bilateral breast cancer) confirmed by biopsy in 5 (3.5%) patients. Of the examined 195 postoperative patients PET/CT detected axillary lymph nodes in 22 (11%) patients, extra-axillary regional lymph nodes in 21 (10%) patients and distant metastasis in 24 (12%) patients. PET/CT findings altered plans for radiotherapy in 22 (11%) patients and chemotherapy was adapted to the meta-static diseases in 24 (12%) patients. PET/CT was revealed to be superior to conventional imaging modalities for the detection of extra-axillary regional metastatic lymph nodes and distant metastases. These features make PET/CT an essential imaging modality for the primary staging of invasive breast cancer, particularly in patients with clinical stages II and III.

The Invasion and Metastasis Promotion Role of CD97 Small Isoform in Gastric Carcinoma

CD97 is over-expressed in the majority of gastric adenocarcinomas and is associated with its dedifferentiation and aggressiveness. Our previous results demonstrated that out of three CD97 isoforms tested, only the small one was able to promote increased invasiveness in vitro. Based on these data we further aimed to investigate the role of CD97 small isoform in gastric cancer progression in vivo by employing the cells with a stable CD97 small isoform knock-down and an orthotopic gastric cancer mouse model. We could demonstrate that the knock down of CD97/EGF1,2,5, led to a significant decrease in the number of cells penetrating the gelatin coated membrane as compared with control cells. In the gastric cancer mouse model, both the hypodermic and the orthotopic yielded tumor masses of the CD97/EGF1,2,5kd group and were significantly smaller than the control. Metastatic tumor cell number in early metastatic regional lymph nodes on post-operative day 42 was distinctly decreased in the CD97/EGF1,2,5kd group as compared with the SGC-NS group, and was accompanied with the downregulation of CD44, VEGFR, CD31 and CD97. We concluded in this study that CD97 small isoform not only supported gastric cancer local growth, but also promoted metastatic spread in orthotopically implanted mouse model suggesting involvement of the CD97 small isoform in the preparation of (pre)metastatic niche.

Tissue inhibitor of metalloproteinases in oral squamous cell carcinomas – A therapeutic target?

Matrix metalloproteinases (MMPs) are proteases responsible for remodeling the extracellular matrix (ECM) and enabling spreading and metastasis of tumor cells, a common phenomenon in oral squamous cell carcinomas (OSCC). They are strongly blocked by several inhibitors, among which we must highlight, for their specificity and potency, the endogenous tissue inhibitors of metalloproteinases (TIMP-1, -2, -3 and -4). The goal of this paper is to describe the expression of TIMPs in OSCC, determining their relation with clinical, histological and prognostic factors, delving into OSCC regulation mechanisms and discussing the use of exogenous TIMPs to treat this type of tumors. Expression of TIMPs in OSCC is higher in tumors than in normal tissue, which correlates with an increase of metastatic risk and regional lymph node affectation. Although some metalloproteinases inhibitors (MMIs) have shown promising results in the treatment of these tumors, their use in OSCC has not been widely tested; and although some indirect MMIs, like COX-2 inhibitors, flavonoids and endostatin seem to have beneficial effects on the invasive capacity of OSCC through regulation of MMPs and TIMP levels, routine clinical use has not been accepted yet.

Feasibility study of neoadjuvant chemoradiotherapy with cisplatin plus 5-fluorouracil and elective nodal irradiation for stage II/III esophageal squamous cell carcinoma.

130 Background: Based on the JCOG 9907 trial results, neoadjuvant chemotherapy with cisplatin (CDDP) plus 5-fluorouracil (5-FU) is considered a standard treatment for stage II/III esophageal squamous cell carcinoma (ESCC) in Japan. However, patient survival remains unsatisfactory. We conducted a feasibility study of neoadjuvant chemoradiotherapy (NeoCRT) with CDDP plus 5-FU and elective nodal irradiation for stage II/III ESCC. Methods: Eligibility criteria included clinical stage II/III (UICC 6th, non-T4) ESCC, PS 0-1, and age 20–75 years. Chemotherapy consisted of 2 courses of 5-FU infusion (1000 mg/m2, days 1–4) and a 2-h CDDP infusion (75 mg/m2, day 1), with a 4-week interval. Radiotherapy was concurrently administered to a total 41.4 Gy in 23 fractions for primary tumor, metastatic lymph nodes and regional lymph nodes. After completion of CRT, transthoracic esophagectomy with extensive lymphadenectomy (>D2) was performed. The primary endpoint was the completion rate of NeoCRT and R0 resection. Results: From July 2010 to June 2011, 33 patients were enrolled, including 2 ineligibles. In 31 eligible patients, the median age was 63 years (range, 40–73); male/female: 28/3; PS0/1: 19/12; cStage IIA/IIB/III: 2/10/19. During CRT, the most common grade 3 or 4 toxicities were leukopenia (65%), neutropenia (65%), anemia (13%), thrombocytopenia (13%), febrile neutropenia (13%), anorexia (16%), esophagitis (16%), and hyponatremia (16%). In total, 31 patients (100%) underwent CRT and 25 (81%) underwent surgery; 1 patient (3%) did not undergo surgery due to disease progression, and the other 5 patients (16%) are scheduled for surgery. Among patients who underwent surgery, there was 1 treatment-related death, and the incidence of operative morbidity was similar to that in previous studies. According to RECIST, the overall response rate was 63% after CRT completion. Pathological complete response was achieved in 11 patients (44%) who underwent esophagectomy. Conclusions: NeoCRT was well tolerated and appears to be highly promising. The randomized controlled trial compared with neoadjuvant chemotherapy is needed and will be started.

Use of detailed pathologic characteristics of the primary colorectal tumor to predict outcome after hepatectomy for metastases.

559 Background: Outcome after hepatic resection for colorectal liver metastases (CRLM) is heterogeneous and accurate predictors of survival are lacking. The aim of our study was to analyze the prognostic relevance of pathologic details of the colorectal primary tumor in patients undergoing hepatic resection of CRLM. Methods: Retrospective review of a prospective database identified patients who underwent potentially curative hepatic resection of CRLM. Clinicopathological variables were investigated and their association with outcome was analyzed. Results: From 1997-2007, 1004 patients underwent hepatic resection for CRLM. The median follow-up for survivors was 59 months with a 5-year predicted survival of 47%. Ninety-two percent of patients received perioperative chemotherapy and 34% received adjuvant hepatic artery infusion chemotherapy. Univariate analysis identified 10 factors associated with poor survival. Three of these related to the pathology of the primary tumor: lymphovascular invasion (LVI, p<0.0001), perineural invasion (p=0.005), and degree of regional lymph node involvement (N0 vs N1 vs N2, p<0.0001). Multivariate analysis identified 7 factors associated with poor survival. Two of these related to the pathology of the primary tumor: LVI (HR 1.3, 95% CI 1.06-1.64, p=0.01) and degree of regional lymph node involvement where an increase in the number of metastatic regional lymph nodes from N1 (HR 1.3, 95% CI 1.04-1.69, p=0.02) to N2 (HR 1.7, 95% CI 1.27-2.21, p <0.0005) was associated with a reduced survival. LVI positive patients had a median survival of 48 months compared to 69 months for LVI negative patients (p<0.0001); moreover, patients who were LVI positive with N2 nodal disease had a reduced survival to 40 months compared to 74 months for patients who were LVI negative with no nodal disease (p<0.0001). Conclusions: Resection of CLRM is associated with long-term survival. Pathologic details of the primary colorectal tumor, particularly LVI and the degree of lymph node involvement, are strong predictors of survival. Future biomarker studies should consider utilizing factors related to the primary colorectal tumor.

Solitary Extramedullary Plasmacytoma of the Thyroid Gland

Solitary extramedullary plasmacytoma of the thyroid gland is an uncommon condition. Up to date, its clinical pathological features are not fully understood. We present a case of an extramedullary nonmucosal plasmacytoma of the thyroid gland which is the first case with regional metastatic lymph nodes. This condition requires a scrupulous survey to rule out a metastatic multiple myeloma. Although localized forms management is still controversial, authors require combined approach for regional metastatic forms. The prognosis is favorable compared to solitary bone plasmacytomas or multiple myeloma.

Prise en charge des cancers du rectum localement avancés : quel rôle pour le pathologiste en 2011 ?

Locally advanced rectal cancers mainly correspond to lieberkünhien adenocarcinomas and are defined by T3-T4 lesions with or without regional metastatic lymph nodes. Such tumors benefit from neoadjuvant treatment combining chemotherapy and radiotherapy, followed by surgery with total mesorectum excision. Such a strategy can decrease the rate of local relapse and lead to an easier complementary surgery. The pathologist plays an important role in the management of locally advanced rectal cancer. Indeed, he is involved in the gross examination of the mesorectum excision quality and in the exhaustive sampling of the most informative areas. He also has to perform a precise histopathological analysis, including the determination of the circumferential margin or clearance and the evaluation of tumor regression. All these parameters are major prognostic factors which have to be clearly included in the pathology report. Moreover, the next challenge for the pathologist will be to determine and validate new prognostic and predictive markers, notably by using pre-therapeutic biopsies. The goal of this mini-review is to emphasize the pathologist's role in the different steps of the management of locally advanced rectal cancers and to underline its implication in the determination of potential biomarkers of aggressiveness and response.

CyclinD1, p53, E‐cadherin, and VEGF discordant expression in paired regional metastatic lymph nodes of esophageal squamous cell carcinoma: A tissue array analysis

The correlation of biomarker expression between primary tumors and corresponding metastases has not yet been well reported in esophageal squamous cell carcinoma (ESCC). This study was to confirm whether primary ESCC tumors differ from their regional metastatic lymph nodes (RMLN) in CyclinD1, p53, E-cadherin, and vascular endothelial growth factor (VEGF) expression and determine prognostic value of their alteration. There were 134 patients with stage T3N1-3M0 ESCC recruited for the research. Expression of CyclinD1, p53, E-cadherin, and VEGF was evaluated in primary ESCC tumors and their paired RMLN assembled on tissue microarrays by immunohistochemistry (IHC). The comparison of expression in different lesion and their correlation with prognosis was analyzed. E-cadherin was discordant expression in 55.2% cases and appeared to be more frequently positive in metastatic lymph nodes (P < 0.001). The VEGF expression level was significantly higher in primary tumors (P < 0.001). Combined analysis of VEGF expressions in paired lesions (P = 0.003) and its decreased expression (P = 0.006) were both predictive. Biomarker expression was discordant between the primary tumor and its paired lymphatic metastasis in over 25% of patient with ESCC. VEGF discordant expression was a new prognostic factor and combined analysis of expression in paired lesions was useful to predict. Analysis of protein expression only in primary tumors would be inadequate to judge prognosis.

The N‐Classification for Esophageal Cancer Staging: Should it be Based on Number, Distance, or Extent of the Lymph Node Metastasis?

The recently published AJCC-TNM staging system for esophageal carcinoma made an obvious modification on N-classification based on the number of metastatic regional lymph nodes (LN). However, this classification might ignore the site at which these LNs occur, a factor that might be even more important in reflecting patients' prognosis. A retrospective study of 236 patients with carcinoma of thoracic esophagus who underwent esophagectomy between 1984 and 1989 with each at least six LNs removed was conducted, with a 10-year follow-up rate of 92.4%. The proposed scheme for N-classification according to the number (0, 1-2, 3-6, ≥7; N0-3), distance (0, 1, 2, 3 stations; S0-3), or extent (0, 1, and 2 fields; F0-2) of LN involvement was evaluated by univariate and multivariate survival analysis. The LN metastasis was identified in 112 patients, revealing a poorer 5-year survival in this patient group when compared to patients without node involvement. Cox regression analysis revealed that the number and distance of LN metastases and the number of metastasis fields were factors significantly influencing survival. When these factors were further analyzed by univariate log-rank test, no significant difference in survival existed between N2 and N3 patients, or among S1, S2, and S3 patients. When patients were grouped according to the extent of LN metastasis, significant differences in survival were observed overall and between each subgroup. Refining the current N-classification for esophageal cancer according to the extent of LN metastasis, rather than by number alone, might be a better means of staging that could subgroup patients more effectively and result in different rates of survival.

Hounsfield units upon PET/CT are useful in evaluating metastatic regional lymph nodes in patients with oesophageal squamous cell carcinoma

This study evaluated the usefulness of measurements of X-ray attenuation (in Hounsfield units) obtained from unenhanced CT images for attenuation correction of the positron emission tomography (PET) data from PET/CT in the assessment of regional lymph node metastasis in oesophageal squamous cell carcinoma. 17 patients with oesophageal squamous cell carcinoma underwent surgery after evaluation with PET/CT. After the excised lymph nodes were reviewed, we compared the histopathology and PET/CT findings, and analysed the lymph node metastasis. When 18-F fludeoxyglucose (FDG) uptake in the lymph nodes was focally prominent in comparison with background mediastinal activity (regardless of lymph node size), the lymph nodes were considered to be positive for malignancy by PET/CT. The mean Hounsfield units of mediastinal lymph nodes showing abnormally increased FDG uptake in PET/CT was retrospectively evaluated using images from the unenhanced CT component of PET/CT. Receiver operating characteristic (ROC) curve analysis was applied to determine the optimal cut-off value of mean Hounsfield units for detecting individual lymph node metastases. For depiction of malignant nodal groups in each lymph node group, the sensitivity, specificity and accuracy of PET/CT based on increased FDG uptake were 58.8%, 74.5% and 70.8%, respectively. For patients with nodal groups that were positive for uptake by PET/CT, the mean attenuation in lymph nodes as measured by CT was 48 ± 13 HU for malignant nodes and 75 ± 18 HU for benign nodes. This difference was statistically significant (p<0.001). Using ROC curve analysis, we determined the cut-off as 71 HU. When we excluded lymph nodes with attenuation higher than 71 HU from the nodes determined as malignant by PET/CT, the specificity and accuracy for detecting metastatic lymph nodes improved to 90.9% and 83.3%, respectively. When interpreting lymph node metastasis in oesophageal squamous cell carcinoma using PET/CT, the assumption that any lymph node with mean HU>71 is benign can improve diagnostic accuracy.

MicroRNA let-7a represses chemoresistance and tumourigenicity in head and neck cancer via stem-like properties ablation

Head and neck cancer (HNC) is a prevalent cancer worldwide. Let-7 has been shown to function as a tumour suppressor by regulating multiple oncogenic signalling pathways. However, the role of let-7 in head and neck cancer (HNC) and in HNC-associated tumour initiating cells (TIC) remains unclear. In this study, we first demonstrated that let-7a expression was significantly decreased but that Nanog/Oct4 expression was increased in HNC tissues as compared to adjacent normal cells. Expression of let-7a in recurrent HNC tissue and in regional metastatic lymph nodes of HNC patients was also significantly decreased, but Nanog/Oct4 expression was increased as compared to the expression levels in the parental tumours. Consistently, the stemness genes were significantly up-regulated and let-7a was down-regulated in HNC-ALDH1(+) cells relative to HNC-ALDH1(-) cells. Furthermore, lentiviral-mediated let-7a overexpression could significantly inhibit the stemness signature and the chemoresistant abilities of HNC-ALDH1(+) cells. Most importantly, overexpression of let-7 or knockdown of Nanog in ALDH1(+) cells effectively blocked tumour metastasis and significantly prolonged survival time in ALDH1(+)-transplanted immunocompromised mice. Overall, restoration of let-7a in HNC and HNC-TIC may be a new approach for the therapeutic treatment of HNC in the future. These results show that let-7a negatively modulates the expression of stemness genes and plays a role as a tumour suppressor in HNC by eliminating the putative HNC-TIC population.

Pathologic T0N1 Esophageal Cancer After Neoadjuvant Therapy and Surgery: An Orphan Status

Patients with esophageal carcinoma who appear to have a complete response at the primary tumor site after undergoing neoadjuvant chemoradiotherapy may still have residual disease in regional lymph nodes despite clinically negative restaging (ypT0N1). We hypothesized that these patients would have similar survival to patients with incomplete response to therapy. We reviewed 336 esophageal cancer patients who received neoadjuvant chemoradiotherapy followed by complete resection. We identified 20 patients who obtained complete pathologic response at the primary tumor with persistent metastatic disease to regional lymph nodes (ypT0N1). These patients were compared to 123 patients with pathologic complete response and 193 with partial response for overall survival. Demographics among the three groups of patients were similar except that this cohort of patients with ypT0N1 had higher initial clinical stage (p = 0.013) and had more squamous cell carcinoma pathology (p = 0.005). Eighty-six percent of the ypT0N1 patients who had modern preoperative staging were felt to have clinical complete response. Five-year survival of ypT0N1 patients was intermediate, similar to pathologic partial response stage II patients in both the sixth and seventh editions of the American Joint Committee on Cancer staging criteria. Clinical staging of complete response to chemoradiotherapy may not translate to pathologic complete response. Patients with ypT0N1 disease at resection have intermediate but reasonable survival, justifying an aggressive approach to curative therapy. Future revisions of the staging system should place this group of patients with patients who have metastatic regional lymph nodes, stratified by number of nodes involved.

Evidence for the changes of antitumor immune response during lymph node metastasis in head and neck squamous cell carcinoma

This study aimed to elucidate the differences in antitumor immune responses between primary tumors and metastatic regional lymph nodes in head and neck squamous cell carcinoma (HNSCC). The clonality of tumor-infiltrating lymphocytes in tissue specimens from 17 HNSCC patients was examined regarding their T-cell receptor (TCR) repertoires and their complementary determining region 3 (CDR3) size spectratyping. Cytokine expression profiles and T-cell phenotypes also were measured by using real-time quantitative polymerase chain reaction. The host immune responses to HNSCC cells, reflected by the TCR repertoire, differed between primary tumors and metastatic lymph nodes. CD8+-T cells and T helper type 1 (TH1)/T cytotoxic 1 (TC1) cell cytokine production in metastatic and nonmetastatic lymph nodes were similar. The antitumor immune response to HNSCC cells changes during lymph node metastasis, and HNSCC cells can escape the cytotoxic immune responses mediated by CD8+-T cells and TH1/TC1 cells. These results suggest that lymph node metastasis might be associated with changes in the nature of the primary tumor antigens.

Gastrointestinale Tumoren

Removal and examination of regional lymph nodes play an important role in the surgical therapy of gastrointestinal tumors concerning potential adjuvant treatment strategies. The number of metastatic regional lymph nodes as well as the number of removed and examined lymph nodes are of importance regarding estimation of the prognosis. It is essential to consider which lymph nodes are defined as regional in the UICC TNM classification and which definitions apply for the individual N categories. Furthermore, it is necessary to define which recommendations are valid for the minimum numbers of lymph nodes to be removed and examined for particular tumor entities.

Ultrasonographic findings validity in the identification of metastatic regional lymph nodes in patients with cutaneous melanoma

BACKGROUND/AIM. Early identification of lymph node (LN) metastases has both therapeutic and prognostic significance in patients with cutaneous melanoma. Ultrasonographic (US) examination of LN morphological characteristics and US of LN morphological and vascular characteristics are diagnostic methods used in identification of regional LN metastases, thus rendering a base for lymphonododisection indication. The aim of this study was to determine validity of these two US diagnostic methods and eventual statistically significant difference between them. METHODS. The study included the two groups of the patients with clinical stage III melanoma. The group I included 31 patients followed up by the use of US of LN morphological characteristics due to the fact that US findings described them only. The group II included 30 patients in whom morphological and vascular LN characteristics were followed up. The patients of both groups were examined in the Institute for Radiology, Military Medical Academy using an ultrasonographic unit type Akuson Sequoia Model 2000. After that, therapeutic and elective radical disections were performed. Sensitivity, specificity and accuracy of US examination of LN were checked by histopathological examination. The presence of LN metastases in the group I was suggested by LN enlargement and its extent, while in the group II it was suggested by the ratio of LN length and width in 83.3% of the patients, echogenicity of LN center in 76.7% of the patients, LN resistance index in 73.3% of the patients, pathologic LN vascularization in 86.7%, and pathologic intranodal arborization in 83.3% of the patients. In 67.7% of the patients in the group I and in 93.3% of the patients in the group II matastatic changes of LN were diagnosed by pathohistology. A difference between validities of the two groups was statistically significant (p < 0.05). LN size without other US morphological and vascular characteristics of LN does not provide enough valid US finding for a reliable preoperative identification of LN with metastatic changes in patients with cutaneous melanoma.

Androgen Deprivation Therapy for Node-Positive Prostate Cancer: Adjuvant Does Not Mean Salvage

TO THE EDITOR: I read with interest the study by Wong et al on the role of androgen deprivation therapy (ADT) in patients who had metastatic regional lymph nodes after radical prostatectomy. As mentioned by the authors, the results of the randomized trial by Messing et al showing a significant advantage in progression-free survival and overall survival in patients who received immediate (rather than delayed at time of metastasis) ADT have led to the standard use of adjuvant ADT for node-positive patients. However, this study was conducted before the prostate-specific antigen (PSA) era and the contemporary practice of surveillance policy with salvage ADT at biochemical recurrence. Therefore, the benefit of adjuvant ADT is not clear, and additional investigations are required. Unfortunately, the methodology used by Wong et al does not allow any useful conclusion to be drawn. Indeed, the major limitation is the absence of data regarding PSA values at onset of ADT. Was ADT administered as an adjuvant treatment in patients who achieved undetectable PSA after surgery or as salvage treatment in patients with biochemical recurrence? For an adjuvant therapy, the choice of 120 days is obviously not optimal. In general oncology, adjuvant treatment is required as soon as possible after local therapy. In prostate cancer, ADT is supposed to be initiated within 8 weeks after surgery (ie, after reaching PSA value 0.1 ng/mL). Therefore, it is highly suspected that patients who received ADT within 120 days of prostatectomy had undetectable (adjuvant ADT) or detectable (salvage ADT) PSA. In my opinion, 150 days or more after prostatectomy, the whole population of patients would have had detectable PSA. Consequently, the reported data do not provide any convincing information regarding the role of adjuvant ADT. The only conclusion can be that in the PSA era, the overall and cancer-specific survivals at 10 years for patients treated with adjuvant ADT or salvage ADT do not seem different from those observed in patients not treated with ADT after prostatectomy.

Intraluminal versus infltrating gallbladder carcinoma:Clinical presentation, ultrasound and computed tomography

To compare clinical presentation and ultrasound (US) and computed tomography (CT) sensitivity between intraluminal and infiltrating gallbladder carcinoma (GBCA). This retrospective study evaluated 65 cases of GBCA that were categorized morphologically into the intraluminal-GBCA (n = 37) and infiltrating-GBCA (n = 28) groups. The clinical and laboratory findings, presence of gallstones, gallbladder size, T-staging, nodal status, sensitivity of preoperative US and CT studies, and outcome were compared between the two groups. There were no significant differences between the two groups with respect to female predominance, presence of abdominal pain, serum aminotransferases level, T2-T4 staging, and regional metastatic nodes. Compared with the patients with intraluminal-GBCA, those with infiltrating-GBCA were significantly older (65.49 +/- 1.51 years vs 73.07 +/- 1.90 years), had a higher frequency of jaundice (3/37 patients vs 13/28 patients) and fever (3/37 patients vs 10/28 patients), higher alkaline phosphatase (119.36 +/- 87.80 IU/L vs 220.68 +/- 164.84 IU/L) and total bilirubin (1.74 +/- 2.87 mg/L vs 3.50 +/- 3.51 mg/L) levels, higher frequency of gallstones (12/37 patients vs 22/28 patients), smaller gallbladder size (length, 7.47 +/- 1.70 cm vs 6.47 +/- 1.83 cm; width, 4.21 +/- 1.43 cm vs 2.67 +/- 0.93 cm), and greater proportion of patients with < 12 mo survival (16/37 patients vs 18/28 patients). The sensitivity for diagnosing intraluminal-GBCA with and without gallstones was 63.6% and 91.3% by US, and 80% and 100% by CT, respectively. The sensitivity for diagnosing infiltrating-GBCA with and without gallstones was 12.5% and 25% by US, and 71.4% and 75% by CT, respectively. In elderly women exhibiting small gallbladder and gallstones on US, especially those with jaundice, fever, high alkaline phosphatase and bilirubin levels, CT may reveal concurrent infiltrating-GBCA.

Integrated FDG-PET/CT compared with intravenous contrast-enhanced CT for evaluation of metastatic regional lymph nodes in patients with resectable early stage esophageal cancer

To assess whether integrated fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) can improve the diagnostic accuracy of metastatic regional lymph nodes (LNs) in esophageal cancer compared with contrast enhanced CT (CECT). We examined 180 consecutive patients with esophageal cancer by integrated PET/CT between April 2006 and March 2007. Eighteen patients (M:F 14:4) underwent radical esophagectomy after evaluations by PET/CT and CECT of 5-7-mm-thick slices 70-80 s after injection. Regional LNs of esophageal cancer were retrospectively reviewed on CECT images by two blinded evaluators on the basis of the following cutoff sizes: 7 mm for all regional LNs (Protocol A), 10 mm for paratracheal LNs (Protocol B), and 7 mm for others. In addition, the maximum standardized uptake value (SUVmax) on PET/CT was evaluated for positive uptake by LNs. Of 210 LNs excised at surgery, 25 were positive and 185 were negative for metastasis at pathology. The PET/CT images identified 15 true-positive and 184 true-negative LNs, whereas CECT identified 15 true positives and 176 true negatives in Protocol A, and 14 true positives and 180 true negative in Protocol B. The sensitivity, specificity, accuracy, positive, and negative predictive values of PET/CT were respectively 60.0%, 99.5%, 94.8%, 93.8%, and 94.8%, whereas those of CECT were 60.0%, 95.1%, 91.0%, 62.5%, and 94.6% (Protocol A) and 56.0%, 97.3%, 92.4%, 73.7%, and 94.2% (Protocol B). A comparison of the two CECT protocols revealed fewer false-positive LNs in Protocol B, but slightly lower sensitivity in Protocol B than in Protocol A. Substantial numbers of false-positive LNs were determined by CECT in the paratracheal regions (6 of 9, 66.7%) and CECT revealed central necrosis in 4 of 15 (26.7%) true-positive LNs > 1.8 cm. The mean SUVmax on PET/CT was 2.9 (range 1.7-5.5) in true-positive LNs. The smallest LN metastasis detectable by PET/CT was 6 mm. Integrated PET/CT improves the PPV of regional LNs when compared with CECT.

Carcinoma ex pleomorphic adenoma of the submandibular gland: report of a case with an unusual malignant component of clear cell squamous cell carcinoma

A large carcinoma ex pleomorphic adenoma (CXPA) with regional lymph node metastasis occurred in the left submandibular gland of a 64-year-old man. Initially, the patient underwent tumor extirpation and ipsilateral radical neck dissection. Histologic examination revealed the malignant component of CXPA was clear cell squamous cell carcinoma (SCC), which is quite uncommon in head and neck region. In the metastatic regional lymph nodes, aggregates of clear cells were observed. To the best of our knowledge, this is the first case of CXPA of which the malignant component is clear cell SCC. Four months after the postoperative radiotherapy, delayed regional metastasis became evident in the contralateral side of the neck. Radical neck dissection was carried out, and, microscopically, moderately differentiated SCC was identified. The patient recovered well and remained free of disease for 29 months after the second surgery.

Comparison of Her-2, EGFR and Cyclin D1 in Primary Breast Cancer and Paired Metastatic Lymph Nodes: An Immunohistochemical and Chromogenic In Situ Hybridization Study

The significant advance in the development of molecular-targeting drugs has made an evaluation of Her-2, EGFR, and cyclin D1 an important clinical issue in breast cancer patients. This study compared the Her-2, EGFR, and cyclin D1 status of primary tumors as well as their matching lymph node metastases using immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH) in 73 breast cancer patients. Her-2, EGFR, and cyclin D1 protein showed a concordance between the primary lesion and the metastatic regional lymph nodes in 82%, 90%, and 63%, respectively. CISH also revealed 92%, 93%, and 85% concordance in the gene amplification status of Her-2, EGFR, and cyclin D1, showing a reasonable agreement between primary tumors and metastatic regional lymph nodes. Although a statistically significant agreement was found in Her-2 expression, a relatively high discordance rate (18%) raises a little concern. Our findings suggest that the Her-2 status can be reliably assessed on primary tumor but a possible difference can be found in Her-2, EGFR, and cyclin D1 status between the primary and the metastatic sites and this possibility should be concerned in patients considering molecular targeted therapy or patients with progress of disease.