06.03 Gene-expression Classifier Testing in the Management of Cytologically Indeterminate Thyroid Nodules.

Posted on January 25, 2017

M. Affi1, B. Javorsky1, T. Yen1, K. Doffek1, B. Hunt1, P. Tolat1, T. Carroll1, T. Giorgadze1, A. Carr1, D. Evans1, T. Wang1  1Medical College Of Wisconsin,Milwaukee, WI, USA

Introduction:  Up to 30% of thyroid nodules evaluated by fine needle aspiration (FNA) are indeterminate on cytology. Use of a 167 gene mRNA-based gene-expression classifier (GEC) test has been shown to have a high negative predictive value for benign nodules and a 40% malignancy rate for GEC-suspicious nodules. The aim of this study was to determine the rate of malignancy in thyroid nodules indeterminate on initial cytology that underwent repeat FNA in anticipation of GEC testing. 

Methods:  This is a retrospective review of all patients with thyroid nodules with indeterminate cytology ('atypia/follicular cells of unknown significance’ or ‘suspicious for follicular neoplasm’) and who underwent GEC testing between 10/12-5/16. Prior to GEC testing, repeat FNA was performed and cytology results were reviewed by an independent cytologist; only indeterminate samples underwent GEC testing. Patients with GEC-benign nodules were recommended for surveillance. Patients with re-classified cytology that was 'suspicious for malignancy' or GEC-suspicious nodules were referred for thyroidectomy. The rate of clinically significant malignancy (>1cm) in patients undergoing thyroidectomy was determined, based on both initial cytology and results of GEC testing.

Results: 89 patients met inclusion criteria. Independent review of cytology yielded 35 (39%) benign, 48 (54%) indeterminate, 2 (2%) suspicious for malignancy, and 4 (5%) non-diagnostic samples. Of the 35 patients with benign cytology, 2 (6%) underwent thyroidectomy with benign final histopathology. The 2 patients with suspicious cytology had a clinically significant papillary thyroid cancer on final histopathology. Of the remaining 52 samples, 46 had sufficient mRNA for GEC analysis; 17 (37%) were GEC-benign and 29 (63%) were GEC-suspicious. None of the patients with GEC-benign lesions have had surgery; to date, 6 (35%) patients have had no changes on follow-up ultrasound. Of 26 patients with GEC-suspicious samples who underwent thyroidectomy, 18 (69%) had benign pathology, 5 (19%) had a clinically significant malignancy, and 3 (12%) patients had an incidental malignancy. Overall, 32 (36%) patients underwent thyroidectomy; based on the original institutional cytological diagnosis of ‘indeterminate,’ the rate of clinically significant malignancy was 22% (7/32).  

Conclusion: Of the 89 patients with indeterminate initial cytology, repeat FNA with cytological review and GEC testing altered the management of 52 (58%) patients. The clinically significant malignancy rate for GEC-suspicious thyroid nodules was 19%, much lower than the reported 40% rate and equivalent to our institutional rate of malignancy in patients with indeterminate nodules who underwent surgery. Further follow-up of nonsurgical patients with GEC-benign nodules is required to determine the true benefit of GEC testing in patients with cytologically indeterminate thyroid nodules at our institution.

 

06.02 Novel MicroRNA Expression Patterns of Breast Cancer to Predict Survival

Posted on January 25, 2017

T. Kawaguchi1, L. Yan2, Q. Qi2, S. Liu2, K. Takabe1  1Roswell Park Cancer Institute,Breast Surgery, Department Of Surgical Oncology,,Buffalo, NY, USA 2Roswell Park Cancer Institute,Department Of Biostatistics & Bioinformatics,Buffalo, NY, USA

Introduction:
MicroRNAs (miRNAs) are small non-coding RNAs that exert its functions by regulating expression of their target genes. Dysregulations of miRNAs are related with breast cancer (BrCa).The purpose of this study was to classify BrCa with miRNAs expression patterns to predict survival utilizing The Cancer Genome Atlas (TCGA).

Methods:
Both clinical and miRNA-seq data enrolled in TCGA dataset were retrieved from the GDC data portal for analyses, and were evaluate by hierarchical clustering based on bioinformatics analysis. We also evaluate clinical relevance including prognostic analysis based on the novel subclasses using the Cox proportional hazard model. 

Results:
Of 1097 cases enrolled in TCGA dataset, 1052 caseswere used for miRNAs expression data and survival analysis. We devided the cases into “short” (died within 3 years after diagnosis), “long” (lived longer than 5 years), and the others. We identified that 15 miRNAs (let-7a-1, miR-106a, miR-17, miR-184, miR-18a, miR-193a, miR-19a, miR-20a, miR-20b, miR-362, miR-4661, miR-500a, miR-766, miR-92a-1, miR-93) were significantly differently expressed between the long and short group. With the expression pattern of these 15 miRNA, the patients were classified into three clusters. Of the 15 miRNAs, we conducted additional feature selection in a multivariate Cox proportional hazard model, and three miRNAs remain after model selection (miR-106a, miR-766, and miR-93). We generated a risk scoring model with the expression of the three miRNAs based on Cox proportional hazard model. We found that the patients with the high score significantly associated with poor outcome. 

Conclusion:
We demonstrated a novel concept that microRNA expression patterns of BrCa can predict worse survival.
 

06.01 Hospital Variation in Neoadjuvant Therapy for T1-2 Pancreatic Cancer: Short and Long-term Outcomes

Posted on January 25, 2017

M. A. Healy1, S. Shubeck1, W. Burns1, T. L. Frankel1, H. Nathan1  1University Of Michigan,Department Of Surgery,Ann Arbor, MI, USA

Introduction:  The benefit of neoadjuvant therapy for resectable pancreatic cancer (PanCa) is controversial, and its use varies significantly between centers. It is unknown whether neoadjuvant therapy practices are associated with short- and long-term patient outcomes across institutions. We sought to evaluate whether institutions that routinely use neoadjuvant therapy achieve superior aggregate outcomes for PanCa patients. 

Methods:  Using the National Cancer Data Base Participant User File, we identified patients with non-metastatic T1-2 PanCa diagnosed from 2006-2013. Hospitals were stratified into quintiles based on risk- and reliability-adjusted rates of neoadjuvant therapy use in resected patients (including chemotherapy and/or radiation). Post-operative and survival outcomes were compared between hospitals using neoadjuvant therapy frequently (Neo-Hi) vs infrequently (Neo-Lo).

Results: We identified 20,646 patients with median age 72 years and 25% T1 tumors. Among 815 treating hospitals, adjusted rates of neoadjuvant therapy varied almost 30-fold (2.9%-83%). Patients at Neo-Hi vs Neo-Lo hospitals had higher readmission rates (8.8% vs 7.4%; P<0.01) but similar 30-day mortality (6.0% vs 5.8%;P=0.6). Neo-Hi vs Neo-Lo hospitals had lower surgical margin positivity (17% vs 21%; P<0.001) and node positivity (56% vs 63%; P<0.001). Resected patients at Neo-Hi vs Neo-Lo hospitals had marginally improved adjusted overall survival at 2 years (48% vs 51%) but not at 5 years (22% vs 22%) (overall HR 0.92, P<0.05). When patients who received systemic therapy but did not ultimately undergo resection were included, there was also no difference in survival (HR 0.98, P=0.3).

Conclusion: Hospitals that use neoadjuvant therapy more frequently in T1-2 PanCa demonstrate lower rates of nodal and margin positivity in resected patients. When patients receiving systemic therapy without ultimately undergoing resection are included, there is no survival difference across hospitals, although these patients may be spared surgical morbidity. Institutional practices regarding neoadjuvant therapy for PanCa do not result in improved aggregate outcomes.

05.12 Treating Pediatric Hydrocephalus in Sub-Saharan Africa: Outcomes After Shunt Placement

Posted on January 25, 2017

S. Scarlet1, J. Gallaher1, A. Charles1  1University Of North Carolina At Chapel Hill,Acute Care Surgery/General Surgery,Chapel Hill, NC, USA

Introduction:  The prevalence of hydrocephalus is greatest in developing countries, where access to neurosurgical care is limited. Hydrocephalus is the most common indication for pediatric neurosurgery worldwide. Untreated disease is associated with severe neurological disability and a high mortality rate. Additionally, there is paucity of data regarding the long-term outcomes of children following ventriculoperitoneal (VP) shunt placement. 

Methods:  We completed a retrospective review of all children diagnosed with hydrocephalus from March 2015 until June 2016 at Kamuzu Central Hospital (KCH) in Lilongwe, Malawi.

Results: Hydrocephalus was diagnosed based on clinical exam, ultrasound, and measurement of intracerebral pressure via ventricular aspiration in 100 children (45% female). All children underwent VP shunt placement during the 17-month study period. Average age at diagnosis was 4.9 months (SD 5). Presenting signs were enlarged head circumference (94%), seizure disorder (22%), irritability (26%) and meningitis (24%). At the time of surgery, mean weight was 6.3 kg (SD 2.5) and mean head circumference was 52.1 cm (SD 8.6). Mean post-operative length of stay was 27 days (SD 14). Crude in-hospital mortality was 4%. Five children required shunt revision for exposed shunt (n=4) and occluded shunt (n=1). 43 patients had follow-up at home within six months of VP shunt placement. 22 children (51%) died within the six-month follow-up period. Among children who had follow-up, a higher mean head circumference (cm) to weight (kg) ratio was associated with late mortality, 10.2 vs. 7.5 (p=0.01).

Conclusion: In sub-Saharan Africa, the high prevalence of pediatric hydrocephalus is attributed to higher birth rates, poor prenatal care, and increased likelihood of meningitis in the perinatal and neonatal period. In our study, the follow-up mortality rate was very high, especially for patients with a high head circumference to weight ratio. More research is needed to determine the appropriate patient population and optimal time for VP shunt placement in a resource-poor setting.

 

05.05 Injury Characteristics, Risk Factors and Outcomes Following Falls in Sub-Saharan Africa

Posted on January 25, 2017

B. E. Haac1,4, J. Gallaher3,4, A. Geyer5, L. Banza2, A. Charles2,3  4UNC Project,Lilongwe, LILONGWE, Malawi 5Air Force Institute Of Technology,Statistics,Wright-Patterson AFB, OHIO, USA 1University Of Maryland Medical Center,General Surgery,Baltimore, MD, USA 2Kamuzu Central Hospital,Surgery,Lilongwe, , Malawi 3University Of North Carolina At Chapel Hill,General Surgery,Chapel Hill, NC, USA

Introduction:   Fall-related injuries are a leading cause of Years Lived with Disability (YLDs) worldwide, yet there remains a dearth of research on predictors of outcomes for falls in low- and middle-income countries. We aimed to further delineate risk factors and outcomes related to fall-related injuries in a Sub-Saharan African cohort.

Methods: We examined the trauma registry at an urban tertiary-care hospital in Malawi for patients presenting after a fall from 2010 to 2014. Categorical and continuous variables were compared with chi-squared and student t-tests, respectively. Logistic and linear regressions were then conducted to assess for the magnitude of effect and control for confounders. A p-value <0.05 was considered significant. 

Results: Over the study time period, 73,267 patients presented with trauma. Falls were the most common mechanism of injury (28.9%), followed by traffic accidents (25.6%), and assault (24.3%). Children (age<18yo; OR 5.10), elderly (age>60yo; OR 1.16), and female (OR 1.57) patients had the highest risk of fall (p<0.001).

The three most severe injuries on presentation and the most common operations differed significantly between patients with falls compared to those suffering from other injury mechanisms (p<0.01). Those with falls had more fractures (aOR 1.82), contusions (aOR 1.86), and dislocations (aOR 2.26), and underwent more open reduction internal fixations and other orthopaedic surgeries (p<0.01).

Patients with falls had a longer mean length of stay (14.8 vs. 12.9 days, p<0.001) and lower mortality (0.4% vs. 3.9%, p<0.01). They were also less likely to be admitted to the hospital (14.4% vs. 18.8%, p<0.001).

Of patients who presented after fall, those who died were older, had higher fall heights, and lower GCS on presentation (p<0.001). Males (p<0.001) and patients who were transferred from another health care facility (p=0.002) had a higher death rate. Patients with flank/abdominal (p<0.001) or head injuries (p<0.001) or those requiring tracheostomy (p<0.001), external-fixation (p=0.042) or amputation (p<0.001) were also more likely to die. In multivariate logistic regression analysis, occupation of peasant farmer (aOR 18.91) or housekeeper/gardener/guard (aOR 16.11) and injuries occurring during the hot dry season (aOR 3.56) were associated with increased death when controlled for confounding in patients who were alive on presentation (p<0.05). Head injury (aOR19.70, p<0.001) was also associated with increased death rates when including patients who were brought-in-dead.

Conclusion: Risk factors for fall include age, sex, occupation, and season. The longer length of stay and lower mortality may be predictive of falls being a significant cause of YLDs after discharge. Age, injury pattern and season were predictive of need for surgery and hospital outcomes including death. Interventions to reduce fall-risk, and improve fall outcomes should focus on these areas.

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