Occult Tumor Research Articles

Pancreatic Neuroendocrine Tumors - Case Series and Literature Review.

Background: Neuroendocrine tumors (NETs) are a heterogeneous group of tumors with various clinical manifestations and biological behavior. Among the most common neuroendocrine tumors (NETs) are pancreatic neuroendocrine tumors (PNETs). They are considered to be relatively rare tumors; however, more recent studies on NET epidemiology have demonstrated an increasing incidence and prevalence over the past 30 years. Aims: We intend to compare the strategy used in a real life clinical environment in the case of pancreatic neuroendocrine tumors, as opposed to an ideal model, as presented in literature. Materials and methods: Our case series consist in 18 patients with neuroendocrine pancreatic tumors diagnosed and treated in the Surgery I department of Clinical Hospital Dr. I. Cantacuzino over a 10-year period (2009-2018). We made a retrospective analysis of these patients, of their diagnosis particularities and choice of treatment and a review of the literature. Results: Out of these 18 cases, 13 had functioning tumors (11 insulinomas and 2 gastrinomas) and 5 non-functioning tumors. Most of the tumors were located in the tail of the pancreas (12 cases) the others were located in the body (1 cases) and the head of the pancreas (5. cases). Surgical treatment consisted in 10 enucleations (3 of them laparoscopic) and 8 pancreatic resections, 2 of them associated with splenectomy and in one case a liver metastasectomy was also performed. The mean follow-up was 12 months. No local or distant recurrences were found with one exception, one female which presented after one year with a cephalic pancreatic tumor that proved to be an adenocarcinoma. Conclusions: Diagnosis of PNETs may be difficult even in the presence of a hormonal hypersecretion syndrome. Nuclear imaging with octreotide is useful for locating the tumor and also for the detectionof any possible occult tumors which cannot be identified through the use of conventional imaging. All PNETs should be considered as potentially malignant, and the use of the term benign should be particularly avoided, which is why tumor grading based on the mitotic count and Ki-67 index must be established for every case. Surgical treatment remains the only with curative potential.

Transoral Robotic Surgery and the Unknown Primary

Carcinoma of unknown primary (CUP) comprises approximately 1%–5% of all head and neck malignancies. Primary site detection rates for metastatic cervical squamous cell carcinoma (SCC) remain variable, with current diagnostic imaging unable to identify all tumours. Prevailing evidence suggests that most head and neck CUP are located in the oropharynx. Diagnostic surgical efforts have been directed at sampling the entire oropharynx. Present techniques that make this possible include transoral robotic surgery (TORS). TORS Lingual tonsillectomy or tongue base mucosectomy performed in the setting of head and neck CUP increases the detection rate of occult tumour. The indication, surgical technique, evidence base, and controversies of performing TORS in the context of the unknown primary are presented.

Dynamics of Genome Alterations in Crohn's Disease-Associated Colorectal Carcinogenesis.

Purpose: Patients with inflammatory bowel diseases, that is, ulcerative colitis and Crohn's disease (CD), face an increased risk of developing colorectal cancer (CRC). Evidence, mainly from ulcerative colitis, suggests that TP53 mutations represent an initial step in the progression from inflamed colonic epithelium to CRC. However, the pathways involved in the evolution of CRC in patients with CD are poorly characterized.Experimental Design: Here, we analyzed 73 tissue samples from 28 patients with CD-CRC, including precursor lesions, by targeted next-generation sequencing of 563 cancer-related genes and array-based comparative genomic hybridization. The results were compared with 24 sporadic CRCs with similar histomorphology (i.e., mucinous adenocarcinomas), and to The Cancer Genome Atlas data (TCGA).Results: CD-CRCs showed somatic copy-number alterations (SCNAs) similar to sporadic CRCs with one notable exception: the gain of 5p was significantly more prevalent in CD-CRCs. CD-CRCs had a distinct mutation signature: TP53 (76% in CD-CRCs vs. 33% in sporadic mucinous CRCs), KRAS (24% vs. 50%), APC (17% vs. 75%), and SMAD3 (3% vs. 29%). TP53 mutations and SCNAs were early and frequent events in CD progression, while APC, KRAS, and SMAD2/4 mutations occurred later. In four patients with CD-CRC, at least one mutation and/or SCNAs were already present in non-dysplastic colonic mucosa, indicating occult tumor evolution.Conclusions: Molecular profiling of CD-CRCs and precursor lesions revealed an inflammation-associated landscape of genome alterations: 5p gains and TP53 mutations occurred early in tumor development. Detection of these aberrations in precursor lesions may help predicting disease progression and distinguishes CD-associated from sporadic colorectal neoplasia. Clin Cancer Res; 24(20); 4997-5011. ©2018 AACR.

FA06.02: OPTIMAL EXTENT OF LYMPH NODE DISSECTION FOR ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Abstract Background The possible presence of occult tumor dissemination is the rationale of radical systematic lymphadenectomy. Theoretically, the more extent of lymphadenectomy, the more similar survival outcomes between node-negative and node-positive patients. Accordingly, there will be a certain number of examined lymph nodes (NELN) for patients with only one tumor-positive lymph node that can equal their survival with the node-negative patients, and this cut-off point should be define the minimal requirement for an adequate extent of lymphadenectomy. The aim of this report was to determine the optimal number of examined lymph nodes (NELN) dissection for esophageal squamous cell carcinoma (ESCC) by this novel method. Methods We retrospectively reviewed 589 ESCC patients from June 2011 and July 2012. Among them, 372 patients were pathologically confirmed with node-negative (N 0 + ), and 217 patients with only one tumor-positive lymph node (N 1 + ). Comparison of overall survival were performed using the Kaplan-Meier method. Cox regression hazard model was used for multivariate analysis to assess the independent influence of NELN on overall survival. Results The median survival for N 0 + and N 1 + patients was 32 versus 23 months (HR 1.61; 95% CI 22.86- 29.148; P = 0.000). Survival analyses revealed that the NELN positively correlated with overall survival (OS) both for patients with N 0- (P = 0.024) and N 1 + (P = 0.046), and an independent prognostic predictor only for N 0 + patients (hazard ratio 0.984; P = 0.032). When the cut-off point of NELN was set as a value less than 18, stratum analysis within the Kaplan–Meier method showed that NELN did not affect the results that N 1 + patients have a worse overall survival as compared with N 0 + patients (P < 0.05). However, stratum analysis showed that no significant difference in OS was observed between N 1 + and N 0 + patients when the NELN was greater than 18. Conclusion The NELN should be considered a mandatory requirement for improving the OS of ESCC patients. The minimum of 18 lymph nodes removed for ESCC is rational and should be complied with. Disclosure All authors have declared no conflicts of interest.

Double contrast-enhanced ultrasound improves the detection and localization of occult lesions in the pancreatic tail: a initial experience report.

The aim of this study is to review our initial experience of Double contrast-enhanced ultrasonography (DCEUS) in the preoperative detection of pancreatic tail occult tumors. Thirty-five patients were recruited to undergo DCEUS of the pancreas suspected by occult lesions of pancreatic with MRI or clinical evidence. The radiologists assessed the images (conventional US, DCEUS, and MRI) for enhancement phases, tumor presence, location, enhancement characteristics, and tumor conspicuity. The differences in the onset times of the phases between DCEUS and MRI were noted. Tumor conspicuity was graded on a four-point scale for conspicuity comparison among three imaging modalities. Pancreatic tail tumors were missed on conventional transabdominal US in 11 of 35 patients. DCEUS revealed 12 lesions of 35 patients. Pancreatic tail tumors were identified on MRI in 10 of 35 patients. The sensitivity and specificity of DCEUS for depicting occult lesions of ≤ 2.2cm were 92% and 95%, respectively. In contrast, the sensitivity and specificity of conventional US were 67% and 66%, respectively. The sensitivity and specificity of MRI were 91% and 88%, respectively. The conspicuity ratings of the three phases did not significantly differ between the DCEUS and MRI groups (P > 0.05). The DCEUS phases started much earlier than the corresponding MRI phases. DCEUS is a promising technique in the detection of occult pancreatic tail tumors and is possibly superior to dynamic enhanced MRI in the case of some peripheral lesions.

Carcinoma of Unknown Primary in Head and Neck Region.

Carcinoma of unknown primary (CUP) in head and neck region is diagnosed in 5% of patients with malignant tumour of head and neck. In the management of patients with CUP, complex investigation to diagnose the occult tumour is always necessary. Detection of origin allows targeted specific treatment that significantly improves the prognosis of the disease. Retrospective analysis of patients treated at the Department of Otorhinolaryngology and Head and Neck Surgery of the UK JLF and UNM in Martin between January 2012 until September 2017 for CUP in head and neck region. Diagnostic procedure and success of primary tumour detection were evaluated. In study group, there were 40 patients with average age 59.4 ± 1.5 years (35-78 years). CT scan and panendoscopic examination in general anaesthesia were performed in all patients. Ipsilateral tonsillectomy (TE) was performed in 34 patients (80%). For the remaining 6 patients, TE was not indicated - 2 found originally in the panendoscopic examination and in 4 TE was performed in the past. Blinded samples from the nasopharynx, the base of the tongue and the pyriform recess were taken in 38 patients (95%). PET/CT screening was indicated in 12 patients (30%). The primary tumour did not detect the primary tumour in any of them. Primary tumour was diagnosed in 21 cases (52.5%). In 16 patients (40%), the primary tumour was found in the upper aerodigestive tract, in 5 patients (12.5%) the primary tumour was located outside the ENT region. The primary tumour was not identified in 19 cases (47.5%). Despite the modern imaging and endoscopic methods, the primary tumour cannot always be identified.

Mifepristone in the treatment of the ectopic adrenocorticotropic hormone syndrome.

Mifepristone, a glucocorticoid receptor antagonist, can be used to manage hypercortisolism in patients with ectopic adrenocorticotropic hormone syndrome (EAS) when surgical cure is not feasible. Outcomes of EAS patients treated with mifepristone have been limited to reports of isolated cases. We aimed to determine the efficacy and limitations of mifepristone in the treatment of EAS and to compare outcomes with those of patients who underwent bilateral adrenalectomy. A retrospective cohort study of EAS patients from the University of Michigan between 1997 and 2017 was conducted. Of the 55 patients with EAS, 16 were treated with mifepristone: eight neuroendocrine tumours, two carcinomas and six occult tumours. Treatment with mifepristone was most commonly prompted by psychosis, uncontrolled glucose and/or hypertension. The median maintenance dose was 600mg/d. Amelioration of psychosis was observed within 48hours in 3/3 patients, and the glycaemic control was improved in 14/16 patients. The median duration of treatment was 9months, and three patients were treated for more than 24months. The overall survival at 24months was equivalent between patients with EAS treated with mifepristone vs bilateral adrenalectomy (N=12) (P=0.6). Mifepristone is effective in treating EAS for over 2years, and survival was not different from that of patients treated with bilateral adrenalectomy. Aggressive concomitant therapy for hypokalaemia and hypertension is necessary.

Survival and Disease-Free Survival by Breast Density and Phenotype in Interval Breast Cancers.

Background: We aimed to evaluate survival and disease-free survival in different subtypes of interval cancers by breast density, taking into account clinical and biological characteristics.Methods: We included 374 invasive breast tumors (195 screen-detected cancers; 179 interval cancers, classified into true interval, false-negatives, occult tumors and minimal-sign cancers) diagnosed in women ages 50-69 years undergoing biennial screening from 2000-2009, followed up to 2014. Breast density was categorized into non-dense (<25% dense tissue) and mixed dense breasts (≥25%). Survival curves were generated by the Kaplan-Meier method and compared by the log-rank test. Cox proportional hazard regression models were computed to estimate the adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs) for death and recurrences by comparing women with interval and true interval cancers versus women with screen-detected cancers, controlling for tumor and patient characteristics. All analyses were stratified by breast density.Results: Interval cancers were detected in younger women, at more advanced stages, in denser breasts and showed a higher proportion of triple-negative cancers, especially among true interval cancers. Women with interval cancer and non-dense breasts had an aHR for death of 3.40 (95% CI, 0.92-12.62). Women with true interval cancers detected in non-dense breasts had the highest adjusted risk of death (aHR, 6.55; 95% CI, 1.37-31.39).Conclusions: Women with true interval cancer in non-dense breasts had a higher risk of death than women with screen-detected cancers.Impact: These results support the advisability of routinely collecting information on breast density, both for further tailoring of screening strategies and as a prognostic factor for diagnosed breast cancers. Cancer Epidemiol Biomarkers Prev; 27(8); 908-16. ©2018 AACR.

Abstract 942: Sensitive detection of microsatellite instability (MSI) in tumors and liquid biopsies using nuclease-based enrichment

Abstract The role of MSI in colorectal cancer (CRC) is well characterized, and colon tumors are classified as MSI-High or MSI-Stable by screening specific microsatellites. MSI-H compared to MSI-S is predictive for therapy outcome in chemotherapy and immunotherapy and has been associated with distinct characteristics and favorable results including better prognosis, a higher 5-year survival, and lesser metastasis. Several other tumors also present MSI changes reflecting mismatch repair deficiency. While tumor testing is the gold standard, a convenient approach to screen for MSI before and during cancer treatment is screening circulating DNA (liquid biopsy) using a blood draw, thereby interrogating ‘systemic' MSI reflecting primary or secondary (occult) tumor status at the time of blood collection. However, presence of excess unaltered, wild-type DNA often masks alterations such as MSI. Using capillary electrophoresis or next generation sequencing for MSI detection presents challenges at low levels of MSI due to polymerase slippage (‘stutter') that generate high false positive rates at positions of homo-polymers. We present a new approach for enrichment of altered micro-satellites prior to DNA-amplification thereby facilitating their detection. We recently developed nuclease-assisted minor-allele enrichment with probe-overlap, a single-step approach that removes WT-DNA and enriches mutation-containing alleles. Here we adapted NaME-PrO for detection of homopolymer indels, for MSI detection. The method employs a double-strand-DNA-specific nuclease and overlapping oligonucleotide-probes interrogating multiple micro-satellite targets. Following DNA denaturation, the probes form double-stranded regions with their targets, thereby guiding nuclease digestion to selected sites. Microsatellite indels create ‘bulges' that inhibit digestion, thus subsequent amplification yields DNA with microsatellite alterations enhanced at multiple targets. The assay is applied at the genomic or circulating-DNA level prior to amplification, thereby avoiding polymerase-introduced ‘stutter peaks' arising from WT DNA. Inclusion of organic solvents allows homogeneous application of the method in closed tube reactions. We validated the method by evaluating 5 MSI targets simultaneously, NR27, NR21, NR24, BAT25 and BAT26 using DNA from tumor biopsies and circulating-DNA from colorectal cancer patients. The technique enriched all altered targets and detected microsatellite alterations down to 0.01% altered allele frequency, thus improving detection sensitivity by &amp;gt;100-fold relative to current approaches. We anticipate application of this highly- multiplex-able method either with standard 5-plex reactions in conjunction with capillary electrophoresis or with NGS-based detection of MSI on thousands of targets to enable sensitive detection in tumors and liquid biopsies. Citation Format: Ioannis Ladas, Chen Song, Fangyan Yu, Ka Wai Leong, Katerina Troullinou, Matthew Kulke, Harvey Mamon, Mike G. Makrigiorgos. Sensitive detection of microsatellite instability (MSI) in tumors and liquid biopsies using nuclease-based enrichment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 942.

Abstract 948: Preventing estrogen receptor alpha-positive breast cancer outgrowth with the use of hormone replacement therapy

Abstract Menopause occurs in all women, usually between the ages of 45 and 55. As a result of menopause, women often experience undesirable vasomotor symptoms, which can be alleviated by hormone replacement therapy (HRT). The Women's Health Initiative (WHI) trial concluded that PremPro, a HRT formulation that combines conjugated equine estrogens (CE) with medroxyprogesterone acetate, increases the risk of breast cancer. Over the years, the number of women taking HRT has dramatically decreased due to the perceived risk based largely on the results of the WHI trial. Follow-up sudies suggest that breast cancer cases from PremPro treatment were primarily due to the outgrowth of occult tumors, not the formation of new disease. Duavee, a more recent form of HRT that combines CE and bazedoxifene (BZA), a selective estrogen receptor modulator (SERM) and degrader (SERD), has been approved by the FDA for treatment of moderate to severe hot flashes and to reduce the risk of osteoporosis. More importantly, this CE+BZA mixture not only relieves symptoms associated with menopause, but it also does not stimulate the breast or uterus. Several preclinical studies suggest that CE+BZA might be protective in the breast, however the mechanism of action of this new combination therapy is not known. Our goal, therefore, is to elucidate the underlying molecular mechanisms by which CE+BZA differentially affects estrogen receptor alpha (ERα) action in the mammary gland, using transcriptome and whole genome occupancy analysis in breast cancer cell lines. RNA-Seq and ChIP-Seq studies suggest that CE+BZA decreases pathways related to S-phase entry, cell cycle regulation and BRCA1. We are also studying the effects of CE+BZA on early mammary cancer progression in the estrogen-sensitive polyoma middle T antigen (PyMT) transgenic mouse model and have observed that treatment with CE+BZA delayed the onset of tumors and decreased their rate of growth. Mice treated with CE+BZA also survived longer. In addition, CE+BZA was able to decrease the rate of tumor growth in an ERα-positive patient-derived xenograft (PDX) mouse model. An improved understanding of the molecular mechanisms of CE+BZA action in hormone sensitive breast cancer cell and animal models should have important implications for women considering HRT. Citation Format: Anna G. Dembo, Emily S. Aledort, Geoffrey L. Greene. Preventing estrogen receptor alpha-positive breast cancer outgrowth with the use of hormone replacement therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 948.

Are Mammographically Occult Additional Tumors Identified More Than 2 Cm Away From the Primary Breast Cancer on MRI Clinically Significant?

To evaluate the clinical significance of mammographically occult additional tumors identified more than 2cm away from the primary breast cancer on preoperative magnetic resonance imaging (MRI). An Institutional Review Board approved review of consecutive preoperative breast MRIs performed from 1/1/08 to 12/31/14, yielded 667 patients with breast cancer. These patients underwent further assessment to identify biopsy proven mammographically occult breast tumors located more than 2cm away from the edge of the primary tumor. Additional MRI characteristics of the primary and secondary tumors and pathology were reviewed. Statistical analysis was performed using SPSS (v. 24). Of 667 patients with breast cancer, 129 patients had 150 additional ipsilateral mammographically occult tumors that were more than 2cm away from the edge of the primary tumor. One hundred twelve of 129 (86.8%) patients had one additional tumor and 17/129 (13.2%) had two or more additional tumors. In 71/129 (55.0%), additional tumors were located in a different quadrant and in 58/129 (45.0%) additional tumors were in the same quadrant but ≥2cm away. Overall, primary tumor size was significantly larger (mean 1.87± 1.25 cm) than the additional tumors (mean 0.79 ± 0.61cm, p < 0.001). However, in 20/129 (15.5%) the additional tumor was larger and in 26/129 (20.2%) the additional tumor was ≥1cm. The primary tumor was significantly more likely to be invasive (81.4%, 105/129) compared to additional tumors (70%, 105/150, p = 0.03). In 9/129 (7.0%) patients, additional tumors yielded unsuspected invasive cancer orhigher tumor grade. The additional tumor was more likely to be nonmass lesion type (37.3% vs 24% p = 0.02) and focus lesion type (10% vs 0.08%, p < 0.001) compared to primary tumor. Mammographically occult additional tumors identified more than 2cm away from the primary breast tumor on MRI are unlikely to be surgically treated if undiagnosed and may be clinically significant.

Prospective Evaluation of Intrahepatic Microscopic Occult Tumor Foci in Patients with Numerous Colorectal Liver Metastases

Background: Patients with numerous colorectal liver metastases (CLM) have high risk of early recurrence after liver resection (LR). The presence of intrahepatic occult microscopic metastases missed by imaging has been hypothesized, but it has never been assessed by pathology analyses. Methods: All patients with > 10 CLM who underwent LR between September 2015 and September 2016 were considered. A large sample of liver without evidence of disease (“healthy liver”) was taken from the resected specimen and sent to the pathologist. One mm-thick sections were analyzed. Any metastasis, undetected by preoperative and intraoperative imaging, but identified by the pathologist was classified as occult microscopic metastasis. Results: Ten patients were prospectively enrolled (median number of CLM n = 15). In a per-lesion analysis, the sensitivity of computed tomography and magnetic resonance imaging was 91 and 98% respectively. The pathology examination confirmed all the CLM. All patients had an adequate sample of “healthy liver” (median number of examined blocks per sample n = 14 [5–33]). No occult microscopic metastases were detected. After a median follow-up of 15 months, 5 patients were disease-free. Recurrence was hepatic and bilobar in all patients. Conclusions: Clinically relevant occult microscopic disease in patients with numerous CLM is excluded. These results support the indication to resection in such patients and exclude the need for de principe major hepatectomy to increase the completeness of surgery.

Two types of ectopic Cushing syndrome or a continuum? Review.

Two types of ectopic Cushing syndrome (ECS) are described: ECS associated with aggressive neoplasms, and ECS with indolent and occult tumors, however, there is a lack of studies that thoroughly review their characteristics. A systematic review was carried out on PUBMED of all the papers about the ECS, in order to better define the types of this subcategory of Cushing's syndrome, highlighting the differential aspects between these subgroups. It was found that in 50% of cases the prototypic "aggressive" ECS is caused by small cell lung carcinomas (SCLC). In these cases, the clinical presentation may be atypical, predominating the signs and symptoms derived from the protein catabolism. Cortisol and ACTH levels are extremely high, the clinical presentation is abrupt (< 3-6months) and the tumor is usually advanced, being impossible a curative treatment. On the other hand, "indolent" ECS is mainly represented by carcinoid tumors (CT). In these cases the clinical presentation overlaps enormously with that of Cushing's disease (CD). Cortisol and ACTH levels are slightly elevated, the clinical presentation is progressive (> 6months) and the prognosis is usually good, and a curative treatment is possible in about 75% of the cases. Although there is no absolute differentiation between the two extremes of ECS, a classification could be established in two groups, guided by its clinical and biochemical characteristics, and mainly by the type and stage of the ACTH-secreting tumor. However, a small percentage of tumors do not fit in this simple grouping, and may present both phenotypes or an intermediate one.

Abstract OT2-02-01: Brazilian randomized study - Impact of preoperative magnetic resonance in the evaluation for breast cancer conservative surgery (BREAST-MRI trial)

Abstract Background: A precise preoperative evaluation of the tumor is essential to improve breast cancer surgical management. Currently, mammography associated with ultrasound and clinical exam are the standard techniques for evaluating extension and tumor localization. However, approximately one third of the lesions in patients eligible for conservative surgical treatment are misevaluated by these methods. Breast magnetic resonance imaging (MRI) has a high sensitivity (95-100%) in detecting invasive neoplasms, and is able to detect occult tumors, multifocal and/or multicentric disease, and contralateral breast cancer more accurately than mammography and ultrasound. Until now, there are only three randomized trials assessing the role of preoperative MRI. These trials have different designs and contradictory results. Trial design: BREAST-MRI is a randomized, open label, unblinded trial designed to compare the accuracy of breast MRI in the preoperative planning of surgical treatment of breast cancer to standard protocol (clinical exam of the breast, mammography and/or breast ultrasound) and the impact of breast MRI on breast cancer outcome. Patients are randomized on a 1:1 basis, stratified for mammary density, into two groups: 1)MRI group: patients are submitted to MRI and standard protocol 2)Control group: standard protocol. First phase: patient recruitment and data collection up until surgery. Second phase: follow-up for five years or until death. Eligibility criteria: women aged 18 years or older with breast cancer stages I to III candidates for conservative surgery (CC). Specific aims: The aim of this study is to evaluate the ability of MRI in selecting patients for conservative treatment of breast cancer. Primary outcomes are: false positive rates, false negative rates, positive predictive value and negative predictive value of MRI in breast cancer CC. Secondary outcomes are: rates of positive margins on pathological examination; reoperation rates; number of conversions to mastectomy; accuracy of MRI according to mammographic density, immunohistochemical subtype and histopathology of the tumor; rates of multicentricity, multifocality and bilateralality of tumors; disease-free survival after 3 and 5 years; and cost-effectiveness of breast MRI. Statistical methods: The calculated total case number for this trial is 372, assuming a recurrence rate of 10% for CC and 1% for mastectomies. The Shapiro-Whilks test will be used to verify if distribution of the quantitative variables follows normal distribution. The baseline population will be analyzed using the t-Student test, or the Mann-Whitney test when appropriate. To test the existence of a possible association between outcomes and the categorized characteristics, chi-square and Fisher's exact test will be performed. Disease progression will be reassessed at 3 and 5 years follow-up, in order to produce a log-rank Kaplan-Meier curve of survival. Present accrual and target accrual: In June 2017, randomizations are at approximately 90% of the target sample size. Citation Format: Dória MT, Mota BS, Reis YN, Ricci MD, Piato JRM, Ferreira VCCS, Shimizu C, Barros N, Filassi JR, Baracat EC. Brazilian randomized study - Impact of preoperative magnetic resonance in the evaluation for breast cancer conservative surgery (BREAST-MRI trial) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT2-02-01.

Paraneoplastic neurological syndromes associated with mediastinal tumors

Clinical presentation of mediastinal tumors may be related to the invasion of the adjacent structures leading, in some cases, to life-threatening emergencies. However in some patients, these tumors may be heralded by non-local symptoms due to paraneoplastic neurological diseases (PND) caused by an autoimmune response to antigens co-expressed by the cancer and the nervous system. PND may affect multiple levels of the nervous system from the cerebral cortex to the neuromuscular junction and the muscle. Early diagnosis of PND can be critical for the detection of a new or recurrent occult tumor. Neural-specific autoantibodies serve as diagnostic markers for PND and in some cases may predict the presence of a specific type of cancer. This review focuses on the clinical and immunological characteristics of the PND associated with the most frequent mediastinal cancers, namely thymoma, lymphoma and germ cell tumors.

Retrospective study of paraneoplastic neurological syndromes in a Chinese Han population from Shandong, East China

ABSTRACTObjective: To analyze the clinical features, diagnostic strategies and therapeutic methods associated with paraneoplastic neurological syndromes.Methods: A retrospective study of paraneoplastic neurological syndromes was performed at a single center in Shandong, East China. The medical records and follow-up data of 28 patients were intensively reviewed between February 2011 and December 2014.Results: Twenty-four (85.7%) patients experienced subacute or chronic onset of disease, and the most common symptoms reported were mild myasthenia and paresthesias. Twenty-five (89.3%) patients presented nervous system lesions prior to occult tumors, and the median time frame between paraneoplastic neurological syndromes onset and the diagnosis of a tumor was 15 weeks. Sensorimotor neuropathy, Lambert-Eaton myasthenic syndrome and limbic encephalitis were the three most common neurological syndromes reported. Elevated serum tumor markers were observed in 44.0% of patients, while 40.7% of patients were positive for onconeural antibodies. Tumors were detected in 21 (75.0%) patients after repeated whole-body screening, and lung carcinomas were the most common primary tumor detected. Seventeen patients received anti-tumor or immunological therapy, and clinical symptoms were relieved in 13 (76.5%) of these patients.Conclusions: In the majority of paraneoplastic neurological syndromes patients, the onset of disease is subacute or chronic with mild clinical symptoms. Nervous system lesions usually occur prior to occult tumors with complicated and various clinical manifestations. Neither tumor markers nor onconeural antibodies exhibit a high rate of occurrence, while repeated whole-body screening is helpful in identifying occult tumors. Early diagnosis and treatment are crucial to these patients.

In the Setting of Negative Mammogram, Is Additional Breast Ultrasound Necessary for Evaluation of Breast Pain?

To evaluate whether in the setting of negative diagnostic mammogram for breast pain additional ultrasound is necessary. Retrospective IRB-approved review of our database identified 8085 women who underwent ultrasound evaluation for breast pain from 1/1/2013-12/31/2013. Of 8085 women, 559 women had mammogram evaluation preceding the ultrasound and these women comprise the basis of this study. The patient's age, type of mammogram examination (screening or diagnostic), Breast Imaging-Reporting and Data System (BI-RADS) breast density (BD), type of breast pain (focal, diffuse, cyclical, unilateral, bilateral), additional breast symptoms (palpable concern, nipple discharge, skin changes, others), mammogram or ultrasound findings and final BI-RADS assessment, follow-up imaging, and follow-up biopsy results were reviewed and recorded. The median age of patients was 46 years old (range: 27-97). Patients recalled from negative screening mammogram were 29.8% (167/559). Patients with preceding negative diagnostic mammogram were 70.2% (392/559). The BI-RADS BD distribution was BD1: 5.5%, BD2: 39.9%, BD3: 46.0%, BD4: 8.6%. Final BI-RADS assessments were BI-RADS 1/2 (79%), BI-RADS 3 (12.9%), BI-RADS 4 (8.1%), BI-RADS 5 (0%). Majority (66.9%, 374/559) of the patient had breast pain alone. Additional breast symptoms were also noted as follows: palpable concern (24%), nipple discharge (3.9%), skin changes or other (5.2%). On follow-up evaluation, 26 findings were recommended for tissue sampling yielding 2 malignancies (0.4%, 2/559) in 2 patients. In the setting of negative mammogram and clinical symptom of breast pain alone yielded no malignances (NPV, 100%, 374/374) and was not impacted by BD. In patients with additional symptoms accompanying pain, malignancies were present despite negative mammogram in 2 patients; nipple discharge (4.5%, 1/22), and palpable concern (0.7%, 1/134). In the setting of negative mammogram and breast pain alone, additional evaluation with ultrasound is likely low yield and may be unnecessary. However, with additional symptoms such as palpable concern or nipple discharge, ultrasound is likely an important adjunct modality for identifying mammographically occult tumors.

Swallowing disorders in cervico-facial tumors – diagnosis and treatment strategy

Oropharyngeal dysphagia is defined by disturbing the passage of the food bowl from the mouth to the esophagus. Swallowing disorders may be the first sign of a tumor pathology in the upper aerodigestive pathways. Sometimes an insidious screening is required in search for an occult primary tumor, representing a complex and difficult approach. In cervical-facial tumor pathology, swallowing disorders are a diagnostic element, a post-therapeutic evolution element, as well as an important element of quality of postoperative life. We present a series of clinical cases that illustrate significantly the importance of swallowing disorders in cervical-facial tumor pathology, referring to the diagnosis stage, but also to the postoperative recovery stage.

Целесообразность выполнения органосохраняющих операций при мультифокальном/мультицентричном раке молочной железы

The incidence of multifocal (MF) and multicentric (MC) carcinomas varies widely among clinical studies, depending on definitions and methods for pathological sampling. Magnetic resonance imaging is increasingly used because it can help identify additional and conven-tionally occult tumors with high sensitivity. However, false positive lesions might incorrectly influence treatment decisions. Therefore, preoperative biopsies must be performed to avoid unnecessary surgery. Most studies have shown higher lymph node involvement rates in MF/MC tumors than in unifocal tumors. However, the rate of local recurrences is usually low after breast conservative treatment (BCT) of MC/MF tumors. It has been suggested that BCT is a reasonable option for MC/MF tumors in women aged 50-69 years, with small tumors and absence of extensive ductal carcinoma in situ. A metaanalysis showed an apparent decreased overall survival in MC/MF tumors but data are controversial. Surgery should achieve both acceptable cosmetic results and negative margins, which requires thorough preoperative radiological workup and localization of lesions. Boost radiotherapy techniques must be evaluated since double boosts might result in increased toxicity, namely fibrosis. In conclusion, BCT is feasible in selected patients with MC/MF but the choice of surgery must be discussed in a multidisciplinary team comprising at least radiologists, surgeons and radiotherapists.

Prognostic Value of Occult Isolated Tumour Cells within Regional Lymph Nodes of Dogs with Malignant Mammary Tumours

Canine mammary tumours (CMTs) are the most common type of neoplasm in bitches. As in women, the presence of metastasis in regional lymph nodes is an important prognostic factor in bitches with mammary carcinomas, but the clinical significance of occult isolated tumour cells (ITCs) within lymph nodes is still undefined in this species. The effectiveness of immunohistochemistry (IHC) in identifying occult ITCs and micrometastasis (MIC) was compared with that of the conventional haematoxylin and eosin staining technique. The relationship between tumour size, histological type, histological grade and the presence of metastasis was evaluated. The overall survival (OS) of female dogs with occult mammary carcinomas and ITCs within lymph nodes was analysed. Fragments of mammary carcinoma and regional lymph nodes of 59 female dogs were also evaluated. Histological sections of mammary carcinoma and lymph node samples were studied for tumour diagnosis and lymph node samples were tested by IHC using a pan-cytokeratin antibody. It was found that 35.2% of occult ITCs and 2.8% of hidden MIC were detected when IHC was used. There was a good correlation between the size of the tumour and metastasis to the lymph nodes (P=0.77). ITCs were observed more frequently in the medullary region (60.7%) and metastases in the cortical region (44.4%). There was no significant difference in the OS between female dogs with occult ITCs and lymph nodes without ITCs. IHC can detect occult tumour cells in lymph nodes that are negative by histopathological examination. Female dogs with nodal ITCs do not have lower survival.