Evidence Of Node Involvement Research Articles

A Multi-Institutional Analysis of Outcomes of Patients with Clinically Node Positive Urothelial Bladder Cancer Treated with Induction Chemotherapy and Radical Cystectomy

Selected patients with bladder cancer with pelvic lymphadenopathy (cN1-3) are treated with induction chemotherapy followed by radical cystectomy. However, the data on clinical outcomes in these patients are limited. In this study we assess pathological and survival outcomes in patients with cN1-3 disease treated with induction chemotherapy and radical cystectomy. Data were collected on patients from 19 North American and European centers with cT1-4aN1-N3 urothelial carcinoma who received chemotherapy followed by radical cystectomy between 2000 and 2013. The primary end points were pathological complete (pT0N0) and partial (pT1N0 or less) response rates, with overall survival as a secondary end point. Logistic regression and Cox proportional hazard ratios were used for multivariate analysis of factors predicting these outcomes. The total of 304 patients had clinical evidence of lymph node involvement (cN1-N3). Methotrexate/vinblastine/doxorubicin/cisplatin was used in 128 (42%), gemcitabine/cisplatin in 132 (43%) and other regimens in 44 (15%) patients. The pN0 rate was 48% (cN1-56%, cN2-39%, cN3-39%, p=0.03). The complete and partial pathological response rates for the entire cohort were 14.5% and 27%, respectively. The estimated median overall survival time for the cohort was 22 months (IQR 8.0, 54). On Cox regression analysis overall survival was associated with pN0, negative surgical margins, removal of 15 or more pelvic nodes and cisplatin therapy. Complete pathological nodal response can be achieved in a proportion of patients with cN1-3 disease receiving induction chemotherapy. The best survival outcomes are observed in male patients on cisplatin regimens with subsequent negative radical cystectomy margins and complete nodal response (pN0) with excision of 15 or more pelvic nodes.

PWE-144 7-year experience of two stage minimally invasive oesophagectomy with intrathoracic anastomosis (mio-2) in a single uk centre

Introduction The 2014 report of the National OesopahgoGastric Cancer Audit (NOGCA) identified an increasing number of patients who were treated with minimally invasive (MIO) or hybrid operations (41.5%). Overall complications were similar to open surgery, but a significant increase in anastomotic leak (AL) after MIO was identified (11.7% vs. 6.7%). Totally minimally invasive oesophagectomy with intrathoracic anastomosis (MIO-2) has been performed at University Hospital Southampton NHS Foundation Trust since 2008 and we present a review of this consecutive series. Method A prospectively collected database of clinic-pathological and operative variables from consecutive patients undergoing oesophagogastric resection between January 1, 2005 and February 27, 2015 was reviewed. Statistical analysis was performed in SPSS. Results 147 patients (78% male, 22% female) underwent MIO-2, beginning in June 2008. Patient demographics were: median age 67 years (33–85), median BMI 26 (16–37), ASA 1 6.8%, ASA 2 64.6%, ASA 3 27.9%, ASA 4 0.7%. One patient had surgery for achalasia and 3 for HGD/Tis; the remainder had invasive cancer. 65% of patients had T3 disease on preoperative staging, with 65.3% having evidence of lymph node involvement (N1+). Median operative duration was 319 min (180–530 min) and median blood loss of 205 ml (0–5000 ml). In 11 (7.5%) cases the thoracic component was converted to open. There were 3 in-patient deaths (2.0%) including one intraoperative mortality. Major complications (Clavien-Dindo 3–4) were observed in 19% of cases with 11 anastomotic leaks (7.5%) and a reoperation rate of 9.6%. An R0 resection was achieved in 81.9% of cases with a median lymph node yield of 21 (2–62). Median length of hospital stay was 11 (6–96) days. Conclusion MIO-2 can be performed in the UK with acceptable perioperative morbidity, mortality, and oncological efficiency. Disclosure of interest F. Noble: None Declared, T. Underwood Grant/Research Support from: MRC, D. Sharland: None Declared, J. Byrne: None Declared, J. Kelly: None Declared.

PTH-322 A single tertiary centre experience of t1 colorectal cancers – a retrospective analysis

<h3>Introduction</h3> The management of T1 colorectal cancer remains controversial and not standardised. Surgical resection can offer cure in the majority of patients and provides appropriate lymph node staging and guides adjuvant treatment. Endoluminal excision has significantly reduced morbidity but risks undertreating undetected lymph node metastases. The aim of this study was to review practice in a single tertiary referral centre over a period of five years. <h3>Method</h3> A retrospective analysis of histology reports, radiology imaging, and electronic records of all confirmed T1 cancers identified on our pathology database was undertaken. Cases between December 2006 and December 2011 were included giving a minimum follow up of 3 years. <h3>Results</h3> There were a total of 71 (47 colon and 24 rectal) T1 cancers that were offered surgical resection. The median age at operation was 66 years (range 36–92). 10 patients (14%) were over the age of 80. Nodal metastases were present in 14 patients (20%). This was higher in rectal cancers than in colon cancers. (33% vs. 13%, p = 0.046). There was one sigmoid cancer staged as T1N2 following sigmoid resection. SM3 invasion and vascular invasion are significantly more likely to be associated with lymph node metastases. (p = 0.048 ad 0.002 respectively). No patients had local recurrences at 3 years. Three patients (4%) had distant metastases at 3 years. One patient had a node negative sigmoid cancer and the other two had rectal cancers one of which was node positive. The cancer specific mortality was 1.4% in this cohort. <h3>Conclusion</h3> In this series lymph node metastases are less common in T1 colonic tumours than in rectal cancers. However, 16 of 24 patients (67%) who underwent a rectal resection for T1 cancers had no evidence of lymph node involvement or vascular invasion. <h3>Disclosure of interest</h3> None Declared.

Low-grade adenosquamous carcinoma of the breast: A diagnostic and clinical challenge

Adenosquamous carcinoma of the breast (ASBC) is a rare variant of metaplastic breast cancer with both glandular as well as squamous differentiation. Their lack of distinct imaging characteristics, sometimes subtle histological characteristics and overlapping features with other benign lesions pose a diagnostic challenge. Unlike other forms of metaplastic breast cancer, low-grade adenosquamous carcinoma (LGAC) tends to follow an indolent course with favourable prognosis. We reviewed eight cases of LGAC in our institution from June 2005 to March 2014. In six cases, LGAC was only found after excisional biopsy. In our patients, LGAC frequently co-existed with other forms of breast pathology. Two patients had incidental findings of LGAC alongside their primary malignant tumour (adenoid cystic carcinoma and invasive ductal carcinoma in one, four foci between 0.5 and 4.0 mm within a radial sclerosing lesion adjacent to a malignant phyllodes tumour in the other). A further four patients had LGAC within a complex sclerosing lesion. One patient had a focus of LGAC within a fibroadenoma. One had a focus of LGAC within a benign phyllodes tumour. None of the patients had evidence of nodal involvement. A high degree of suspicion is recommended as such lesions tend to be incidental histological findings within benign tumours or within complex sclerosing lesions. Although the risk of nodal and distant metastasis is low, the potential for local recurrence necessitates aggressive local excision with margin clearance. The role of axillary dissection has yet to be defined and routine sentinel node biopsy and axillary clearance may not be necessary in view of rarity of nodal metastasis in literature. Benefit from adjuvant radiotherapy or chemotherapy is not clearly defined. All eight patients in our study have shown no evidence of recurrence after definitive surgery but longer periods of surveillance is required.

MP65-01 PELVIC LYMPH NODE DISSECTION ON THE CONTRALATERAL SIDE CAN BE LIMITED IN STRICTLY UNILATERALLY LOCATED BLADDER CANCER

You have accessJournal of UrologyBladder Cancer: Invasive III1 Apr 2015MP65-01 PELVIC LYMPH NODE DISSECTION ON THE CONTRALATERAL SIDE CAN BE LIMITED IN STRICTLY UNILATERALLY LOCATED BLADDER CANCER Bernhard Kiss, Michael Paerli, Daniel Schöndorf, George N. Thalmann, and Beat Roth Bernhard KissBernhard Kiss More articles by this author , Michael PaerliMichael Paerli More articles by this author , Daniel SchöndorfDaniel Schöndorf More articles by this author , George N. ThalmannGeorge N. Thalmann More articles by this author , and Beat RothBeat Roth More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2291AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Dynamic multimodality lymph node (LN) mapping showed contralateral lymphatic drainage of the lateral bladder in 40% of patients but without evidence of drainage to the contralateral internal iliac region. Due to the substantial impact of these findings on nerve sparing in radical cystectomy we evaluated whether patho-anatomical findings confirm these dynamic imaging results in patients with strictly unilaterally located bladder cancer. METHODS Between 01/2000 and 07/2013 825 bladder cancer patients without evidence of LN involvement (cN0) underwent extended pelvic LN dissection (PLND), radical cystectomy, and urinary diversion at our institution. 193/825 (23%) of these cN0 patients turned out to be LN positive in the pathological specimen (pN+). 26% (51/193 patients) of this subgroup had strictly unilaterally located bladder cancer. The distribution of LN involvement in these patients was retrospectively analyzed. RESULTS The median number of LNs removed per patient was 35 (range 13-80). The median number of positive LNs was 2 (range 1-14). Fourteen of 51 patients (31%) presented with LN metastases on the contralateral side (total positive contralateral LNs:18; median 1 LN per patient; range 1-3). 72% (13/18) of the positive contralateral LNs were located in the external iliac, 17% (3/18) in the obturator, and 11% (2/18) in the common iliac region. There was no positive LN found in the contralateral internal iliac region. Five of 51 patients (10%) showed LN metastases only in contralateral external and common nodes without evidence of LN metastases in the ipsilateral pelvis. CONCLUSIONS Crossover lymphatic drainage is a common phenomenon and unilateral PLND would have missed LN metastases in 31% of patients. However, our patho-anatomic mapping study confirms the results of dynamic multimodality LN mapping showing no lymphatic drainage to the contralateral internal iliac region. Thus, if bladder cancer is strictly unilaterally located, contralateral pelvic lymph node dissection can be limited to the obturator fossa, and the external and common iliac regions. Consequently, preserving the contralateral autonomic nerves situated close and medial to the internal iliac vessels does not compromise surgical radicality. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e807 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Bernhard Kiss More articles by this author Michael Paerli More articles by this author Daniel Schöndorf More articles by this author George N. Thalmann More articles by this author Beat Roth More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Merkel cell carcinoma of the upper eyelid: when reconstruction becomes a challenge.

Merkel cell carcinoma of the upper eyelid: when reconstruction becomes a challenge.

The Benefits and Risks of Prophylactic Central Neck Dissection for Papillary Thyroid Carcinoma: Prospective Cohort Study.

Objectives. This study evaluated the benefits of performing prophylactic central neck dissection (CND) with total thyroidectomy (TT) in management of papillary thyroid carcinoma (PTC) patients who were clinically node-negative at presentation. Methods. A total of 257 patients with stage T1 or T2 PTC and without preoperative evidence of lymph node involvement (N0) were enrolled in this prospective study. The patients were randomly assigned to two groups: (1) a total thyroidectomy (TT) group (n = 104) or (2) a TT plus CND group (n = 153). The two groups were compared for their perioperative data, complication rates, disease recurrence rates, and clinical outcomes. Results. The two groups of patients were similar in age, sex ratio, follow-up duration, and tumor size (P = 0.227, 0.359, 0.214, and 0.878, resp.). The two groups showed similar rates of disease recurrence (3.9% in the TT group versus 3.3% in the TT plus CND group); however, complications occurred more frequently in the TT plus CND group; especially transient hypocalcemia (P = 0.043). Conclusions. Patients treated with TT plus CND had a higher rate of complications with similar recurrence rate. We believe that CND may not be routinely recommended when treating patients with PTC.

Abstract 4172: Noncoding mutation analysis reveals previously unrecognized pathways in lymph node-invasive breast cancer

Abstract Large-scale DNA sequencing studies have elucidated genomic landscapes of breast cancer (BC) tumours to identify driver mutations and dysregulated pathways contributing to tumourigenesis. Reported somatic mutations largely consist of protein coding mutations, whereas analyses of mRNA splicing mutations have been limited, even though these mutations are prevalent in many genetic disorders. We conducted an independent study of 445 matched normal and BC tumour exomes from The Cancer Genome Atlas Consortium (TCGA) using software for large-scale prediction and validation of novel splicing mutations. A variant caller, Strelka, was used to detect somatic mutations by comparing matched tumour-normal genotypes. The Shannon Human Splicing Pipeline predicted 5 206 splicing mutations, of which 1 130 are classified as cryptic splice site variants, 1 355 and 2 721 as inactivating or weakening natural sites, respectively. We predicted 385 (90%) of 429 splicing variants reported by the TCGA. Software was developed for high throughput validation of these variants using matched RNA sequencing data and controls to confirm expected consequences due to the variant's effect on the strength of the cognate splice site: cryptic splicing (extension or truncation of an exon), exon skipping or intron inclusion attributable to missplicing. Statistical significance was computed based on counts of the expected isoforms relative to their occurrence in non-variant containing samples. The splicing mutations were found to be in genes previously implicated in BC (TP53, MLL3, CDH1, MAP3K1, PTEN, PIK3CA, GATA3 and RB1) as well as novel significantly mutated genes identified by the TCGA (CBFB, PIK3R1 and NF1). Pathway analysis of mutated genes based on splicing variants alone revealed overrepresentation of 29 pathways including 14 collagen, 4 extracellular matrix (ECM), and other pathways previously associated with BC such as the cell cycle or ERBB2 signaling. Many, but not all, of these pathways were shown to be overrepresented by the TCGA. Inclusion of splicing mutations revealed enrichment in 8 NCAM1 related pathways in samples with evidence of lymph node involvement, which was not observed in the lymph node-negative subset (p &amp;lt; 0.05). NCAM pathway-related mutations explain variability within significant components of the data, and are correlated with tumour stage and receptor status. Based on our findings, we hypothesize that NCAM1 and associated mutations contribute to tumour metastasis, whereas, overall, tumours are enriched for collagen/ECM mutations regardless of lymph node status. A non-negligible fraction of splicing variants are also predicted to overlap codons. We propose that comprehensive reporting of DNA sequencing data should consider both protein coding and non-trivial splicing analyses to avoid missing clinically-significant deleterious splicing mutations, which may contribute to novel metastasis-associated pathways. Citation Format: Stephanie N. Dorman, Coby Viner, Ben C. Shirley, Peter K. Rogan. Noncoding mutation analysis reveals previously unrecognized pathways in lymph node-invasive breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4172. doi:10.1158/1538-7445.AM2014-4172

Membranous Nectin-4 expression is a risk factor for distant relapse of T1-T2, N0 luminal-A early breast cancer.

Nectins are Ca2+-independent immunoglobulin-like cell adhesion molecules that compose a family of four members that regulate several cellular activities such as movement, proliferation, survival, differentiation, polarization, and the entry of viruses. Nectin-4 has recently emerged as a metastatis-associated protein in several cancers. Here, we have evaluated the association between the expression of Nectin-4 and the clinical outcome of patients with node-negative, T1/T2 breast cancers.The study group consisted of 197 patients presenting with primary unilateral breast carcinoma (T1/T2), with no evidence of nodal involvement and distant metastases. Nectin-4 protein expression was assessed by immunohistochemistry on tissue microarrays, and the results correlated with the clinical data using Kaplan–Meier curves and multivariate Cox regression analysis. Thirty-four out of 197 tumors (17.3%) exhibited Nectin-4 expression on cell membrane (m-Nectin-4) and 122 out of the 163m-Nectin-4 negative tumors (74.8%) showed high cytoplasmic expression of Nectin-4 (c-Nectin-4High). At Kaplan–Meier analysis, m-Nectin-4 positivity was significantly associated with a lower disease-free survival (DFS) and distant relapse-free survival (DRFS) rate in patients with a luminal-A phenotype (P=0.030 and P=0.002, respectively). Multivariate analysis showed that in luminal-A tumors m-Nectin-4 positivity is an independent prognostic factor for DFS (P=0.018) and DRFS (P=0.004), but not for local relapse-free survival (LRFS). On the other hand, c-Nectin-4High was significantly associated with higher rates of DFS and LRFS, but not DRFS, in the whole population (P=0.008 and P=0.004, respectively) and in patients with luminal-A tumors (P=0.022 and P=0.018, respectively). In patients with luminal-A tumors, multivariate analysis showed that the prognostic value of c-Nectin-4Low/Negative is limited to DFS (P=0.012) and LRFS (P=0.022). We suggest that Nectin-4 represents a prognostic factor and a therapeutic target in luminal-A early stage breast cancer.

Treatment of rectal cancer by transanal endoscopic microsurgery: experience with 425 patients.

To describe our experience in treating rectal cancer by transanal endoscopic microsurgery (TEM), report morbidity and mortality and oncological outcome. A total of 425 patients with rectal cancer (120 T1, 185 T2, 120 T3 lesions) were staged by digital rectal examination, rectoscopy, transanal endosonography, magnetic resonance imaging and/or computed tomography. Patients with T1-N0 lesions and favourable histological features underwent TEM immediately. Patients with preoperative stage T2-T3-N0 underwent preoperative high-dose radiotherapy; from 1997 those aged less than 70 years and in good general health also underwent preoperative chemotherapy. Patients with T2-T3-N0 lesions were restaged 30 d after radiotherapy and were then operated on 40-50 d after neoadjuvant therapy. The instrumentation designed by Buess was used for all procedures. There were neither perioperative mortality nor intraoperative complications. Conversion to other surgical procedures was never required. Major complications (urethral lesions, perianal or retroperitoneal phlegmon and rectovaginal fistula) occurred in six (1.4%) patients and minor complications (partial suture line dehiscence, stool incontinence and rectal haemorrhage) in 42 (9.9%). Postoperative pain was minimal. Definitive histological examination of the 425 malignant lesions showed 80 (18.8%) pT0, 153 (36%) pT1, 151 (35.5%) pT2, and 41 (9.6%) pT3 lesions. Eighteen (4.2%) patients (ten pT2 and eight pT3) had a local recurrence and 16 (3.8%) had distant metastasis. Cancer-specific survival rates at the end of follow-up were 100% for pT1 patients (253 mo), 93% for pT2 patients (255 mo) and 89% for pT3 patients (239 mo). TEM is a safe and effective procedure to treat rectal cancer in selected patients without evidence of nodal involvement. T2-T3 lesions require preoperative neoadjuvant therapy.

Axillary management in invasive lobular carcinoma: Do we need to re-evaluate the use of sentinel node biopsy?

Introduction: Current NICE guidelines for early invasive breast cancer recommend patients without evidence of lymph node involvement on ultrasound should primarily undergo sentinel lymph node biopsy (SLNB).

Long-term survival of patients receiving multimodality neoadjuvant therapy for resectable or borderline resectable pancreatic ductal adenocarcinoma.

309 Background: While surgery offers the only chance for cure in localized PDA, outcomes remain poor for those who have undergone surgical resection (SR). Neoadjuvant therapy (NATx) has several advantages, including early treatment of micrometastatic disease, the potential for tumor downstaging, and improved selection of patients (pts) for surgery by excluding those with chemotherapy-refractory disease. Methods: We report long-term follow-up on consecutive pts with resectable or borderline resectable (R/BR) PDA treated at our institution with an off-protocol, but defined regimen of multi-modality NATx. Demographic, clinical and outcomes data were extracted from medical records. Overall survival (OS) and progression-free survival (PFS) were calculated by Kaplan-Meier analysis. Results: 16 pts with R/BR PDA were treated with NATx; median follow-up is now 41 months (mo) (7.9-91.5). The median age was 57, 50% were female, and all had an ECOG PS &lt;2. Fourteen (88%) had BR disease, and 9 (56%) had radiographic evidence of nodal involvement. All pts received NA gemcitabine, docetaxel and capecitabine and 13 (81%) also received NA chemoradiotherapy with capecitabine +/- oxaliplatin. 14 pts (88%) underwent SR; of those, 11 (79%) received adjuvant chemotherapy. The median decline in CA19-9 over the course of NATx was 80%. An R0 resection was achieved in 11 pts (79%), and there were 2 pCR. To date, 12 pts have died, 4 are alive (including 2 with CA19-9 &gt;1000 at dx), and 3 are without recurrence. The mPFS and mOS were 27.4 and 41 mo, respectively. 1- and 3-year survival rates were 94% and 56%, respectively. When analyses were restricted to pts who underwent SR, the mPFS and mOS were 29 mo and 47.8 mo, respectively. There were no surgery-related deaths. 3 pts had postoperative wound complications. Conclusions: In this series of mostly BR pancreatic cancer pts, treatment with multi-modality NATx resulted in an almost doubling of mOS when compared to historical controls. NATx was also safe, and did not increase surgical morbidity or mortality. Based on these encouraging results, a phase II protocol of multi-modality NATx for R/BR PDA was initiated and has now completed accrual.

Sentinel Lymph Node Biopsy in Papillary Thyroid Carcinoma

Background: The prognostic value of sentinel lymph node (SLN) biopsy mapping of tumor lymphatics for determining metastases in patients with papillary thyroid carcinoma (PTC) remains unconfirmed. Therefore, this study investigated the reliability and feasibility of the SLN biopsy to predict metastasis in PTC. Methods: Fifty-one PTC patients without clinical evidence of lymph node involvement (cN0) underwent preoperative lymphoscintigraphy with Technetium-99m-labeled dextran. Total or near-total thyroidectomy was performed with SLN biopsy guided by intraoperative injection of methylene blue dye and scanning with a hand-held gamma probe. All patients received selective neck dissections. Results: The SLN was identified by all three methods in all cases (100%). Identification rates for methylene blue dye and lymphoscintigraphy plus probe scanning were 90.2% and 96.1%, respectively. Metastases in SLNs were revealed in 31 and 38 cases by intraopertative frozen sectioning and final pathologic examination, respectively. Sensitivity, specificity, accuracy, and positive and negative predictive values of SLN biopsy were 97.4%, 100%, 98.0%, 100% and 92.3%, respectively. Conclusion: SLN biopsy in patients with cN0 PTC detected occult metastasis with high accuracy and may have the potential to select patients who require selective neck dissection.

Prophylactic Central Neck Dissection Increases the Cost of Thyroid Cancer Care

Over the past several decades, health care spending has risen faster than any other segment of the United States economy and continues to rise. Media attention has been focused on health care costs since the introduction of the Patient Protection and Affordable Care Act of 2010, which aims to reduce costs of health care while improving outcomes. Physicians are in the best position to determine which treatments are effective and which patients benefit most, and they are more cognizant than ever of the mandate to spend our limited health care dollars wisely. Cost minimization should be the goal of every physician, as long as quality of care does not diminish. The incidence of papillary thyroid cancer (PTC) is increasing in the United States, but thankfully survival is excellent compared with many other cancers. Patients diagnosed when the disease is limited to the thyroid gland are nearly always cured with thyroidectomy. Unfortunately, regional lymph node metastases from PTC are very common, with the majority of patients having at least micrometastatic disease in the central neck at the time of diagnosis. Nodal involvement increases the risk of recurrence, which plays an important role in the long-term management of this disease. While there is no debate about removing clinically apparent lymph node disease at the initial surgery, there is significant debate regarding the utility of performing a prophylactic central lymph node dissection (pCND) as part of the initial thyroidectomy when there is no evidence of lymph node involvement. There has not been a definitive randomized controlled trial to date, and there are strong advocates on both sides of the argument. Proponents claim pCND saves future morbidity of repeat operations without adding much operative risk to the initial operation, while opponents feel it adds operative morbidity without altering long-term outcomes for the majority of patients. Most of the available literature has struggled to address either the risk or the benefit of pCND, and there has been no consensus. Lang et al., in this current issue, aim to answer the question from a costeffectiveness perspective, adding yet another dimension to this debate at a timely moment in national discourse. They report, unsurprisingly, that the initial procedural costs are higher for pCND at the time of initial surgery for node-negative PTC versus performing a simple thyroidectomy alone. The key question is whether that initial investment (and higher costs of more initial complications) saves health care spending in the long term by reducing the rates of reoperations and future complications. Using data from their recent well-done meta-analysis of 14 studies with 3,331 patients, the authors used odds ratios for complications of both initial surgeries, recurrence rates, and the likelihood of radioactive iodine (RAI) treatment to create a mathematical model. This model projected out costs for a hypothetical cohort of 100,000 women with a 1.5-cm papillary thyroid cancer. Using it, they found that pCND is not cost saving and calculated that, over 20 years, the accumulated direct costs of a thyroidectomy with pCND is $3000 more than initially performing a thyroidectomy alone and dealing with recurrences as they arise. In this hypothetical cohort of patients, the higher costs of pCND are mostly attributable to (1) longer operative time and greater complexity of the operation, (2) more initial complications, and (3) higher percentage of postoperative RAI in patients with pCND. Reoperations actually have similar costs in this model, and while fewer This is an editorial to the article available at doi: 10.1245/s10434013-3234-9.

The role of preoperative ultrasound evaluation of inguinal lymph nodes in patients with vulvar malignancy

ObjectivesInguinal lymphadenectomy in vulvar malignancies is associated with significant morbidity, especially in patients over 70years old. Under certain conditions, surgical guidelines recommend biopsy and evaluation of the sentinel node in early vulvar cancer. The purpose of our study is to evaluate ultrasonography as a predictor of inguinal lymph node involvement. MethodsA retrospective study was performed with 60 patients who had vulvar malignancies (92% of which were squamous cell carcinomas) and who were treated at our hospital between 2002 and 2012. The patients ranged in age from 35 to 89years, with a median age of 76years. In total, 118 groin scans were retrospectively evaluated for sonographic evidence of lymph node involvement (i.e., absence of fatty hilum, irregular shape, cortical region diameter and vascularization pattern). The results were then compared with histopathologically confirmed lymph node status. ResultsHistopathologically confirmed lymph node status was available for 107 of the inguinal nodes examined by ultrasound, and lymph node metastases were found in 38 (35.5%) cases. The presence or absence of inguinal lymph node metastases was correctly identified by sonography in 92 (86.0%) of the scanned areas. Sensitivity was 76.3%, specificity was 91.3%, and positive and negative predictive values were 82.9% and 87.5%, respectively. ConclusionsUltrasonography of the inguinal lymph nodes showed a relatively high sensitivity and specificity for predicting inguinal tumor metastases. However, our results indicate that surgical lymph node staging is still needed to precisely determine inguinal lymph node status in vulvar cancer, especially because a missed lymph node-metastasis is often fatal.

Characterisation of antibody responses to Gal-positive and Gal-free biological heart valves

Characterisation of antibody responses to Gal-positive and Gal-free biological heart valves

Comparative analysis of survival, treatment, cost and resource use among patients newly diagnosed with brain metastasis by initial primary cancer

Brain metastases are a frequent complication of many systemic cancers and portend a poor prognosis. This retrospective analysis of health claims data compared survival, treatment and health care utilization and costs in patients with brain metastasis by primary tumor site. Adult commercial and Medicare Advantage enrollees newly diagnosed with brain metastasis in 01 Jan 2004 through 30 Apr 2010 were identified. Inclusion required at least 2 claims that identified the same primary cancer site prior to diagnosis of brain metastasis and no evidence of primary brain tumors. Health care utilization rates and costs were calculated at the patient level for each month of follow-up. Differences among primary cancer site cohorts were assessed by ANOVA (continuous variables), Chi square test (proportions) and the Poisson distribution (utilization rates). The primary cancer cohorts comprised 1,031 lung cancer, 93 melanoma and 395 female breast cancer patients. During the 6 months prior to brain metastasis diagnosis, 59 % of lung cancer patients had no evidence of lymph node involvement or other metastatic disease compared to 55 and 42 % of melanoma and breast cancer patients (P < 0.001). Survival after brain metastasis diagnosis was less than 3 months for 52, 43 and 39 % for lung cancer, breast cancer and melanoma, respectively (P < 0.001). Melanoma patients had the highest rate of inpatient stays and outpatient visits (P ≤ 0.003). Total monthly all-cause costs were: melanoma, $23,426; breast cancer $19,708; lung cancer, $17,007 (P = 0.003). Health care utilization and costs after brain metastasis diagnosis were substantial and differed by primary tumor site.

An ultrasonography-cytology protocol for the diagnostic management of regional nodes in a subset of patients with Merkel cell carcinoma of the skin

The status of regional lymph nodes (LNs) is one of the most consistent predictors of survival in Merkel cell carcinoma (MCC). In cases of clinically localized disease, current practice involves sentinel lymph node (SLN) assessment. To propose ultrasonography (US) followed by fine needle aspiration cytology (FNAC) and immunohistochemistry as a useful diagnostic tool in the pre-surgical management of patients with MCC. US of LNs was performed in 75 patients with MCC (22 with stage III tumours; 53 with stage I-II). In patients with US suspected disease, US coupled with FNAC of the LN was performed. Smears were examined by routine cytological staining supplemented with immunohistochemical staining for cytokeratin 20. All patients underwent surgical removal of regional LNs. In all 22 patients with stage III tumours, US was indicative of tumour deposits and FNAC confirmed metastases to LNs. In 11 of 53 patients with localized MCC without clinical evidence of nodal disease, US revealed enlarged, equivocal nodes where FNAC was performed. Ten LNs were cytologically positive for metastases, and one was negative. Upon histological examination, the FNAC-negative case showed a metastasis 5 mm in diameter. In all the other 42 cases with no clinical or US evidence of LN involvement, only SLN biopsy was performed and in six cases small metastatic foci were detected. Ultimately, of the 53 stage I-II MCC, 17 had positive LN involvement. In 10 cases (59%) metastases were detected by FNAC, and in seven cases, were detected by SLN biopsy. In a selected subset (∼20%) of patients with MCC with clinically localized disease, US followed by FNAC in the suspect LN is a valid alternative to the classical protocol of SLN histological examination.

Can intraoperative frozen section influence the extension of central neck dissection in cN0 papillary thyroid carcinoma?

Ipsilateral central compartment node dissection has been proposed to reduce the morbidity of prophylactic bilateral central compartment node dissection in papillary thyroid carcinoma (PTC), but it carries the risk of contralateral metastases being overlooked in approximately 25 % of patients. We aimed to verify if frozen section examination (FSE) can identify patients who could benefit from bilateral central compartment node dissection. All the consenting patients with clinically unifocal PTC, without any preoperative evidence of lymph node involvement, observed between September 2010 and September 2011 underwent total thyroidectomy plus bilateral central compartment node dissection. Ipsilateral central compartment nodes were sent for FSE. Forty-eight patients were included. Mean number of removed nodes was 13.2 ± 6.8. Final histology showed lymph node metastases in 21 patients: ipsilateral in 15, bilateral in 6. FSE accurately predicted lymph node status in 43 patients (27 node negative, 16 node positive). Five node metastases were not detected at FSE: three were micrometastases (≤ 2 mm). Sensitivity, specificity and overall accuracy of FSE in definition of N status status were 80.7, 100, and 90 %, respectively. FSE is accurate in predicting node metastases in clinically unifocal node negative PTC and can be useful in determining the extension of central compartment node dissection. False-negative results are reported mainly in case of micrometastases, which usually have limited clinical implications.

Overexpression of activated phospholipase Cγ1 is a risk factor for distant metastases in T1‐T2, N0 breast cancer patients undergoing adjuvant chemotherapy

Phospholipase Cγ1 (PLCγ1) is highly expressed in several tumors. We have previously reported that both stable and inducible PLCγ1 down-regulation resulted in an almost complete inhibition of breast cancer-derived experimental lung metastasis formation. The aim of our study is to evaluate the association between the expression of PLCγ1 and of PLCγ1 phosphorylated at Tyr1253 (PLCγ1-pY1253) and at Tyr783 (PLCγ1-pY783) with the clinical outcome of patients with node negative, T1/T2 breast cancers. The study groups consisted of 292 (training set) and 122 (validation set) patients presenting with primary unilateral breast carcinoma (T1-T2), with no evidence of nodal involvement and distant metastases. PLCγ1, PLCγ1-pY1253 and PLCγ1-pY783 protein expression were assessed by immunohistochemistry on tissue microarrays and the results correlated with the clinical data using Kaplan-Meier curves and multivariate Cox regression analysis. Tumor cells while expressing variable proportions of cytoplasmic PLCγ1, express PLCγ1-pY1253 and PLCγ1-pY783 predominantly in the nucleus. High expression of PLCγ1, and of its activated forms, is associated with a worse clinical outcome in terms of incidence of distant metastases, and not of local relapse in T1-T2, N0 breast cancer patients undergone adjuvant chemotherapy. PLCγ1 over-expression appears to be a reliable predictive surrogate marker of development of metastases. Thus, targeting PLCγ1 pathways might represent a potential therapeutic approach for the prevention of metastatic disease in breast cancer.