Risk of Recurrence in Differentiated Thyroid Cancer: A Population-Based Comparison of the 7th and 8th Editions of the American Joint Committee on Cancer Staging Systems.

BACKGROUND: Differentiated thyroid cancer (DTC) survival is excellent, making recurrence a more clinically relevant prognosticator. We hypothesized that the new American Joint Committee on Cancer (AJCC) 8th edition improves on the utility of the 7th edition in predicting the risk of recurrence in DTC. METHODS: A population-based retrospective review compared the risk of recurrence in patients with DTC according to the AJCC 7th and 8th editions using the Surveillance, Epidemiology, and End Results-based Kentucky Cancer Registry from 2004 to 2012. RESULTS: A total of 3248 patients with DTC were considered disease-free after treatment. Twenty percent of patients were downstaged from the 7th edition to the 8th edition. Most patients had stage I disease (80% in the 7th edition and 94% in the 8th edition). A total of 110 (3%) patients recurred after a median of 27 months. The risk of recurrence was significantly associated with stage for both editions (p < 0.001). In the 7th edition, there was poor differentiation between lower stages and better differentiation between higher stages (stage II hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.39-2.11; stage III HR 3.72, 95% CI 2.29-6.07; stage IV HR 11.66, 95% CI 7.10-19.15; all compared with stage I). The 8th edition better differentiated lower stages (stage II HR 4.06, 95% CI 2.38-6.93; stage III HR 13.07, 95% CI 5.30-32.22; stage IV 11.88, 95% CI 3.76-37.59; all compared with stage I). CONCLUSIONS: The AJCC 8th edition better differentiates the risk of DTC recurrence for early stages of disease compared with the 7th edition. However, limitations remain, emphasizing the importance of adjunctive strategies to estimate the risk of recurrence.

Surgical Management of the Axilla in Invasive Lobular Carcinoma in the Z1071 Era: A Propensity-Score Matched Analysis of the National Cancer Database.

In patients with invasive lobular carcinoma (ILC) and clinically positive nodes (cN1) who demonstrate an axillary clinical response to neoadjuvant-chemotherapy (NAC), the outcomes of sentinel lymph node biopsy (SLNB) compared to axillary lymph node dissection (ALND) are not well studied. We sought to evaluate axillary surgery practice patterns and the resultant impact on overall survival (OS) in cN1 ILC. The National Cancer Database (NCDB) was queried (2012-2017) for women with cN1 ILC who were treated with NAC followed by surgery. Propensity-score matching was performed between SLNB and ALND cohorts. Kaplan-Meier and Cox regression analyses were performed to identify predictors of OS. Of 1390 patients, 1192 were luminal A ILCs (85.8%). 143 patients (10.3%) had a complete axillary clinical response, while 1247 (89.7%) had a partial clinical response in the axilla. Definitive axillary surgery was SLNB in 211 patients (15.2%). Utilization of SLNB for definitive axillary management increased from 8% to 16% during the study period. Among 201 propensity-score matched patients stratified by SLNB vs. ALND, mean OS did not significantly differ (81.6 ± 1.8 vs. 81.4 ± 2.0 months; p = 0.56). Cox regression analysis of the entire cohort demonstrated that increasing age, grade, HER2+ and triple-negative tumors, and partial clinical response were unfavorable OS predictors (p < 0.02 each). The definitive axillary operation and administration of adjuvant axillary radiation did not influence OS. In cN1 ILC patients with a clinical response to NAC in the axilla, SLNB vs. ALND did not affect OS. Further axillary therapy may be warranted with ypN+ disease.

Effect of Microporous Polysaccharide Particles in Patients Undergoing Mastectomy.

BACKGROUND: Microporous polysaccharide particles (MPP, proprietary name "Arista AH"), derived from purified plant starch, are used to augment hemostasis at surgery. The effect of MPP regarding short-term complications after mastectomy remains an area of ongoing investigation. PATIENTS AND METHODS: A single-institution, retrospective chart review of patients undergoing unilateral mastectomy without reconstruction from January 2019 to 2021 was performed. Primary endpoints included antibiotic prescription, seroma or abscess drainage, readmission, wound dehiscence, and time to drain removal within 30 days of initial surgery. Wilcoxon rank sum test or Student t test was used for group comparisons for continuous variables; Chi-square test or Fisher exact test was used to evaluate the associations among categorical variables. RESULTS: One hundred ninety patients were included; 119 received MPP and 71 did not. There was no difference in antibiotic prescription, infection drainage, hematoma, readmission, dehiscence, or time to drain removal with regards to MPP use. MPP treated patients were older (65.8 years vs. 59.1, P < .001) and had lower albumin levels (4.1 g/dL vs. 4.3, P = .025). Patients who underwent abscess drainage had higher body mass index ( mean 36.1 vs. 30.1 P = .036). Patients requiring seroma drainage were more likely to be diabetic (12.8% vs. 4%, P = .035) and to have been treated with lymphovenous anastomosis (LVA, 15.6% vs. 3.8%, P = .009). Patients who had LVA were significantly less likely to receive MPP when compared to other groups (3.1% vs. 74.7% P < .001). CONCLUSION: Consider utilizing MPP in patients at higher risk of seroma, such as those undergoing axillary surgery including LVA.

Novel chemotherapeutic agent, FND-4b, activates AMPK and inhibits colorectal cancer cell proliferation.

Colorectal cancer (CRC) is the second leading cause of cancer deaths in the US with the majority of deaths due to metastatic disease. Current chemotherapeutic regimens involve highly toxic agents, which limits their utility; therefore, more effective and less toxic agents are required to see a reduction in CRC mortality. Novel fluorinated N,N'-diarylureas (FND) were developed and characterized by our group as potent activators of adenosine monophosphate-activated kinase (AMPK) that inhibit cell cycle progression. The purpose of this study was to determine the effect of a lead FND compound, FND-4b, either alone or combined with PI-103 (a dual PI3K/mTOR inhibitor) or SN-38 (active metabolite of irinotecan) on cell cycle arrest and apoptosis of CRC cell lines (both commercially-available and novel lines established from our patient population). Treatment with FND-4b for 24h resulted in a marked induction of phosphorylated AMPK expression and a concomitant reduction in markers of cell proliferation, such as cyclin D1, in all CRC cell lines. Apoptosis was also notably increased in CRC cells treated with FND-4b. Regardless of the genetic profile of the CRC cells, FND-4b treatment alone resulted in decreased cell proliferation. Moreover, the combination of FND-4b with PI-103 resulted in increased cell death in all cell lines, while the combination of FND-4b with SN-38 resulted in increased cell death in select cell lines. Our findings identify FND-4b, which activates AMPK at micromolar concentrations, as a novel and effective inhibitor of CRC growth either alone or in combination with PI-103 and SN-38.

Impact of the Affordable Care Act on Colorectal Cancer Screening, Incidence, and Survival in Kentucky.

BACKGROUND: Kentucky ranks first in the US in cancer incidence and mortality. Compounded by high poverty levels and a high rate of medically uninsured, cancer rates are even worse in Appalachian Kentucky. Being one of the first states to adopt the Affordable Care Act (ACA) Medicaid expansion, insurance coverage markedly increased for Kentucky residents. The purpose of our study was to determine the impact of Medicaid expansion on colorectal cancer (CRC) screening, diagnosis, and survival in Kentucky. STUDY DESIGN: The Kentucky Cabinet for Health and Family Services and the Kentucky Cancer Registry were queried for individuals (≥20 years old) undergoing CRC screening (per US Preventative Services Task Force) or diagnosed with primary invasive CRC from January 1, 2011 to December 31, 2016. Colorectal cancer screening rates, incidence, and survival were compared before (2011 to 2013) and after (2014 to 2016) ACA implementation. RESULTS: Colorectal cancer screening was performed in 930,176 individuals, and 11,441 new CRCs were diagnosed from 2011 to 2016. Screening for CRC increased substantially for Medicaid patients after ACA implementation (+230%, p < 0.001), with a higher increase in screening among the Appalachian (+44%) compared with the non-Appalachian (+22%, p < 0.01) population. The incidence of CRC increased after ACA implementation in individuals with Medicaid coverage (+6.7%, p < 0.001). Additionally, the proportion of early stage CRC (stage I/II) increased by 9.3% for Appalachians (p = 0.09), while there was little change for non-Appalachians (-1.5%, p = 0.60). Colorectal cancer survival was improved after ACA implementation (hazard ratio 0.73, p < 0.01), particularly in the Appalachian population with Medicaid coverage. CONCLUSIONS: Implementation of Medicaid expansion led to a significant increase in CRC screening, CRC diagnoses, and overall survival in CRC patients with Medicaid, with an even more profound impact in the Appalachian population.

FFAR4 Is Involved in Regulation of Neurotensin Release From Neuroendocrine Cells and Male C57BL/6 Mice.

Neurotensin (NT), a 13 amino-acid peptide, is predominantly released from enteroendocrine cells of the small bowel in response to fat ingestion. Free fatty acid receptors (FFARs) FFAR1 and FFAR4 regulate secretion of gut hormones and insulin. Here, we show that docosahexaenoic acid, a long-chain fatty acid, has the most dramatic effect on NT release. FFAR1 agonists slightly stimulate and FFAR4 agonists dramatically stimulate and amplify NT secretion. Double knockdown of FFAR1 and FFAR4 decreases NT release, whereas overexpression of FFAR4, but not FFAR1, increases NT release. Administration of cpdA, an FFAR4 agonist, but not TAK-875, a selective FFAR1 agonist, increases plasma NT levels and further increases olive oil-stimulated plasma NT levels. Inhibition of MAPK kinase (MEK)/ERK1/2 decreased fatty acid-stimulated NT release but increased AMP-activated protein kinase (AMPK) phosphorylation. In contrast, inhibition of AMPK further increased NT secretion and ERK1/2 phosphorylation mediated by FFAR1 or FFAR4. Our results indicate that FFAR4 plays a more critical role than FFAR1 in mediation of fat-regulated NT release and in inhibitory crosstalk between MEK/ERK1/2 and AMPK in the control of NT release downstream of FFAR1 and FFAR4.