Disparities in the impact of the AJCC 8th edition staging system on differentiated thyroid cancer outcomes.

BACKGROUND: The impact of AJCC8 among self-reported racial/ethnic groups on differentiated thyroid cancer (DTC) outcomes is unknown. METHODS: Multivariate-regression evaluated the association between AJCC7 to AJCC8 stage change and race/ethnicity in patients with DTC in the NCDB. Cox-proportional-regression evaluated whether AJCC7 to AJCC8 stage change affects overall survival (OS) differently based on reported race/ethnicity. RESULTS: After adjusting for confounders, Hispanics and Asian-Pacific-Islanders (APIs) were 27% and 12% less likely to be down-staged compared to white-non-Hispanics (WNHs) (p < 0.001); black-non-Hispanics (BNHs) had no significant down-staging difference. Down-staged patients had an increased risk of death compared to patients with unchanged staging, regardless of race/ethnicity. However, based on two-way interaction, the magnitude of this negative change on survival from down-staging was only different between WNHs (HR = 2.64) and BNHs (HR = 1.77), (p = 0.04). CONCLUSIONS: Outcome disparities persist among self-reported racial/ethnic groups with AJCC8. Down-staged patients across all racial/ethnic groups had decreased survival compared to those with unchanged stage, with the least impact in BNHs.

Parathyroidectomy for Patients With Primary Hyperparathyroidism and Associations With Hypertension.

Importance: Hyperparathyroidism is associated with cardiovascular disease. However, evidence for a beneficial consequence of parathyroidectomy on hypertension is limited. Objective: To investigate if parathyroidectomy improves hypertension in patients with primary hyperparathyroidism (PHPT). Design, Setting, and Participants: In this cohort study and retrospective database review, patients with PHPT and hypertension between January 1, 2008, and December 31, 2016, were identified. The mean arterial pressure (MAP) and number of antihypertensive medications were compared between those who did and did not undergo parathyroidectomy. The setting was a large health care system. Primary hyperparathyroidism was defined using biochemical data, and hypertension was identified by International Classification of Diseases, Ninth Revision codes. Exposure: Parathyroidectomy was identified in the database by Current Procedural Terminology codes. Main Outcomes and Measures: The MAP and use of antihypertensive medications were compared for patients who underwent parathyroidectomy and those who did not at 6 months, 1 year, and 2 years. Multivariable logistic regression was used to assess the adjusted odds ratios for both increased and decreased use of antihypertensive medications. Results: In this cohort study of 2380 participants (79.0% female), patients undergoing parathyroidectomy (n = 501) were younger (mean [SD] age, 65.3 [9.7] vs 71.9 [10.4] years; P < .001) and took fewer antihypertensive medications at baseline (mean [SD] number of medications, 1.2 [1.1] vs 1.5 [1.3], P < .001) than nonsurgical patients (n = 1879). Patients with parathyroidectomy showed greater improvement in their MAP at all follow-up time points (the median [SD] MAP change from baseline to 1 year was 0.1 [8.7] mm Hg without parathyroidectomy vs -1.2 [7.7] mm Hg after parathyroidectomy, P = .002). Nonsurgical patients were more likely vs those with parathyroidectomy to require more antihypertensive medications at 6 months (15.9% [n = 298] vs 9.8% [n = 49], P = .001), 1 year (18.1% [n = 340] vs 10.8% [n = 54], P < .001), and 2 years (17.6% [n = 330] vs 12.2% [n = 61], P = .004). By multivariable analysis, parathyroidectomy was independently associated with freedom from an increased number of antihypertensive medications at all periods (eg, adjusted odds ratio, 0.49; 95% CI, 0.34-0.70; P < .001 at 1 year). Among patients who were initially not taking antihypertensive medications, patients with parathyroidectomy were less likely vs no surgery to start antihypertensive medication treatment at all periods (eg, 10.2% [13 of 127] vs 30.4% [136 of 447], P < .001 at 1 year). Conclusions and Relevance: This study's findings suggest that, among hypertensive patients with PHPT, parathyroidectomy may be associated not only with greater decreases in their MAP but also with reduced requirements for antihypertensive medications. Parathyroidectomy decreased the number of patients who began taking antihypertensive medications. Additional study will be required to find whether there are downstream cardiovascular benefits of parathyroidectomy. Preexisting hypertension, particularly in those not already taking antihypertensive medications, should be considered when weighing surgical treatment.

Implementation of a Post-mastectomy Home Recovery Program in a Large, Integrated Health Care Delivery System.

BACKGROUND: The number of outpatient mastectomies, with and without reconstruction, has increased nationwide. In well-selected patient populations, same-day surgery for mastectomy is a safe option. A pilot project was initiated within the Kaiser Permanente Northern California healthcare system to facilitate surgical home recovery (SHR) for mastectomy patients, including patients undergoing implant-based reconstruction and bilateral mastectomies. METHODS: Surgical home recovery for mastectomy patients was implemented in October 2017. Specific measures in this initiative included management of patient expectations at initial consultation, education about postoperative home care, multimodality pain management, and timely post-discharge follow-up. All patients undergoing mastectomy were included, except those undergoing autologous tissue reconstructions. After a 6-month implementation period, rate of same day discharge over 6 months was compared before and after the SHR initiative. We also compared emergency department (ED) visits, reoperations, and readmissions within 7 days. RESULTS: Twenty-one medical centers participated in this initiative. Before implementing SHR, 164 of the 717 (23%) mastectomies were outpatient procedures, compared with 403 of the 663 (61%) after the implementation period. Although the rate of outpatient mastectomy increased significantly, there were no statistically significant differences in ED visits (5.2% vs. 5.1%, p = 0.98), reoperation (3.5% vs. 3.5%, p = 0.99), or readmission rates (1.4% vs. 2.7%, p = 0.08). CONCLUSIONS: By implementing standard expectations and sharing best practices, there was a significant increase in the rate of home recovery for mastectomy without compromising quality of patient care. The success of this pilot program supports SHR for mastectomy.

Impact of Effective Systemic Therapy on Metastasectomy in Stage IV Melanoma: A Matched-Pair Analysis.

BACKGROUND: Although resection historically played a prominent role in the treatment of metastatic melanoma, recent advances have altered the therapeutic landscape, and potentially the role of surgery. We examined surgical selection and metastasectomy outcomes before and after the onset of the effective drug therapy era. METHODS: Patients with stage IV melanoma were identified and characterized by treatment era (either 1965-2007 or 2008-2015) and by systemic therapy agents. BRAF and/or MEK inhibitors, as well as checkpoint inhibitors, were included as modern agents. Selection factors for metastasectomy were examined by era. A matched-pair analysis of outcomes of surgical and non-surgical patients receiving modern systemic agents was performed. RESULTS: Among 2353 eligible patients, 1065 (45.2%) underwent surgical treatment. Factors associated with selection for metastasectomy in the early era included female sex, no prior stage III disease, single-organ involvement, and M1a (vs. M1c) disease (all p < 0.007). In the current era, the proportion of surgically treated patients increased modestly (54.5% vs. 44.7%, p = 0.02) and age was the only independent selection factor (p < 0.01). Surgery followed by modern therapy in 47 matched pairs was associated with higher 5-year melanoma-specific survival (MSS) versus modern therapy alone (58.8% vs. 38.9%, p = 0.049). Multivariable regression showed single-organ involvement (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.21-0.90, p = 0.02) and first-line surgery (HR 0.47, 95% CI 0.23-0.98, p = 0.04), as well as use of modern agents (HR 0.29, 95% CI 0.21-0.40, p < 0.001), were independently associated with improved MSS. CONCLUSIONS AND RELEVANCE: While modern systemic agents have improved outcomes in stage IV melanoma, metastasectomy remains associated with favorable survival. Resection remains a viable therapeutic approach, possibly worthy of prospective evaluation.

Epigenomic and Transcriptomic Characterization of Secondary Breast Cancers.

BACKGROUND: Molecular alterations impact tumor prognosis and response to treatment. This study was designed to identify transcriptomic and epigenomic signatures of breast cancer (BC) tumors from patients with any prior malignancy. METHODS: RNA-sequencing and genome-wide DNA methylation profiles from BCs were generated in the Cancer Genome Atlas project. Patients with secondary breast cancer (SBC) were separated by histological subtype and matched to primary breast cancer controls to create two independent cohorts of invasive ductal (IDC, n = 36) and invasive lobular (ILC, n = 40) carcinoma. Differentially expressed genes, as well as differentially methylated genomic regions, were integrated to identify epigenetically regulated abnormal gene pathways in SBCs. RESULTS: Differentially expressed genes were identified in IDC SBCs (n = 727) and in ILC SBCs (n = 261; Wilcoxon's test; P < 0.05). In IDC SBCs, 105 genes were upregulated and hypomethylated, including an estrogen receptor gene, and 73 genes were downregulated and hypermethylated, including genes involved in antigen presentation and interferon response pathways (HLA-E, IRF8, and RELA). In ILC SBCs, however, only 17 genes were synchronously hypomethylated and upregulated, whereas 46 genes hypermethylated and downregulated. Interestingly, the SBC gene expression signatures closely corresponded with each histological subtype with only 1.51% of genes overlapping between the two histological subtypes. CONCLUSIONS: Differential gene expression and DNA methylation signatures are seen in both IDC and ILC SBCs, including genes that are relevant to tumor growth and proliferation. Differences in gene expression signatures corresponding with each histological subtype emphasize the importance of disease subtype-specific evaluations of molecular alterations.

Correlation Between Clinical and Pathologic Staging in Colon Cancer: Implications for Neoadjuvant Treatment.

BACKGROUND: Recent randomized trials suggest improved outcomes in patients with locally advanced colon cancer (LACC) treated with neoadjuvant chemotherapy (NAC). Optimal selection of patients for NAC depends on accurate clinical staging. The purpose of this study was to examine the degree of correlation between clinical and pathologic staging in patients with colon cancer (CC). METHODS: Adult patients with non-metastatic CC who underwent surgery were identified from the National Cancer Data Base between 2006 and 2014. Data on clinical and pathologic staging was obtained. Kappa index was used to determine the correlation between clinical and pathologic staging. RESULTS: One hundred five thousand five hundred sixty-nine patients were identified. The overall correlation rate between clinical and pathologic staging for T stage was 80% (kappa 0.7) and 83% for N stage (kappa 0.6). The correlation rate was 54% for T1, 76% for T2, 95% for T3, and 94% for T4 (P < 0.001). This compared with 81% for N0, 82% for N1, and 97% for N2 (P < 0.001). The sensitivity and specificity of clinical staging for identifying T3/T4 vs T1/T2 were 80 and 98%, respectively, compared to 60 and 98% for N1/N2 vs N0 (P < 0.001). CONCLUSIONS: Our findings suggest that current modalities used for clinical staging are accurate in predicting pathologic stage for advanced but not early T and N disease. Further optimization of clinical staging is essential for the accurate selection of patients who may benefit from neoadjuvant therapy and to avoid overtreatment of low-risk patients.

Current Imaging Modalities Understage One-Third of Patients with Stage I Rectal Cancer: Implications for Treatment Selection.

Accurate preoperative clinical staging is essential to optimize the treatment of rectal cancer. Primary surgical resection is typically indicated for stage I disease, whereas neoadjuvant therapy is recommended for stages II and III. The objective of this study is to examine the accuracy of clinical staging using current imaging modalities in predicting pathologic stage and, thus, selecting appropriate treatment. Adult patients with nonmetastatic rectal cancer who underwent primary surgical resection were identified from the National Cancer Database between 2006 and 2014. Data on clinical and pathologic staging was obtained. Kappa index was used to determine the correlation between clinical and pathologic staging. A total of 13,175 patients were identified. The correlation between clinical and pathologic staging was 69 per cent for stage I (31% upstaged) (Kappa 0.54, P < 0.001). One-third of patients who were clinically staged as stage I, and were therefore treated with primary surgical resection, had pathologic stage II or III disease. Based on their clinical staging, those patients did not receive the neoadjuvant therapy recommended by present guidelines. Where accurate clinical staging is in doubt, oncologists should carefully examine the quality of staging modality and perhaps consider multimodal imaging using both endorectal ultrasound and MRI.

Neoadjuvant Chemotherapy Improves Survival in Patients with Clinical T4b Colon Cancer.

BACKGROUND: In 2016, the National Comprehensive Cancer Network included neoadjuvant chemotherapy as a treatment option for patients with clinical T4b colon cancer. However, there is little published data on the survival impact of neoadjuvant chemotherapy for locally advanced colon cancer. METHODS: Adult patients with non-metastatic clinically staged T3 or T4 colon cancer who underwent surgical resection were identified from the National Cancer Data Base between 2006 and 2014. Treatment was categorized as neoadjuvant chemotherapy followed by surgery and surgery followed by adjuvant chemotherapy. Overall survival was compared between the two groups using propensity score matching. RESULTS: Of 27,575 patients that met inclusion criteria, 26,654 (97%) were treated with surgery followed by adjuvant chemotherapy and 921 (3%) received neoadjuvant chemotherapy followed by surgery. After propensity score matching, patients with T4b colon cancer treated with neoadjuvant chemotherapy had a 23% lower risk of death at 3 years compared to patients that had adjuvant chemotherapy (HR 0.77, 95% CI 0.60-0.98; p = 0.04). However, neoadjuvant chemotherapy did not demonstrate a similar significant benefit for patients with T3 and T4a disease. CONCLUSIONS: Patients with clinical T4b colon cancer treated with neoadjuvant chemotherapy may have an improved survival compared to those who receive adjuvant chemotherapy. Further prospective investigation is warranted.

Survival Analysis with Extended Lymphadenectomy for Gastric Cancer: Removing Stage Migration from the Equation.

The survival benefit of an extended versus standard lymphadenectomy for gastric cancer (GC) is often attributed to upstaging when more lymph nodes (LNs) are removed, i.e., stage migration. An extended lymphadenectomy is defined as 30 or more LNs examined, a surrogate for a D2 dissection. The aim of this study is to examine whether the survival benefit of extended lymphadenectomy persists when stage migration is not possible. The National Cancer Data Base was queried to identify patients with pathologic N3 (pN3, ≥7 positive LNs) gastric adenocarcinoma. Overall survival (OS) was compared by extent of lymphadenectomy (7-14, 15-29, and ≥30 LN) and stratified by T stage. Of 2101 pN3 patients, 419 (19.9%) had 7 to 14 LNs examined, 1164 (55.4%) had 15 to 29 LNs examined, and 518 (24.7%) had ≥30 LNs examined. Unadjusted three-year OS in the entire cohort was 24.6, 27.3, 30.5 per cent for 7 to 14 LNs, 15 to 29 LNs, and ≥30 LNs, respectively (P = 0.003). On adjusted survival analysis by stage for patients with pT1-T2N3 disease, removing ≥30 LNs significantly improved OS compared with removing 7 to 14 LNs (hazard ratio [HR] 2.45, 95% confidence interval = 1.25-4.82, P = 0.009). Extended lymphadenectomy may confer a survival benefit in select patients with pT1N3 and pT2N3 GC, highlighting the importance of the number of LNs examined rather than stage migration on survival. For the majority of the N3 population, pT3-pT4, the extent of lymphadenectomy did not significantly improve the OS.

A Disease-Specific Hybrid Rotation Increases Opportunities for Deliberate Practice.

IMPORTANCE: Incorporating deliberate practice (DP) into residency curricula may optimize education. DP includes educationally protected time, continuous expert feedback, and a focus on a limited number of technical skills. It is strongly associated with mastery level learning. OBJECTIVE: Determine if a multidisciplinary breast rotation (MDB) increases DP opportunities. DESIGN: Beginning in 2010, interns completed the 4-week MDB. Three days a week were spent in surgery and surgical clinic. Half-days were in breast radiology, pathology, medical oncology, and didactics. The MDB was retrospectively compared with a traditional community rotation (TCR) and a university surgical oncology service (USOS) using rotation feedback and resident operative volume. Data are presented as mean ± standard deviation. SETTING: Oregon Health and Science University in Portland, Oregon; an academic tertiary care general surgery residency program. PARTICIPANTS: General surgery residents at Oregon Health and Science University participating in either the MDB, TCR or USOS. RESULTS: A total of 31 interns rated the opportunity to perform procedures significantly higher for MDB than TCR or USOS (4.6 ± 0.6 vs 4.2 ± 0.9 and 4.1 ± 1.0, p < 0.05). MDB was rated higher than TCR on quality of faculty teaching and educational materials (4.5 ± 0.7 vs 4.1 ± 0.9 and 4.0 ± 1.2 vs 3.5 ± 1.0, p < 0.05). Interns operated more on the MDB than on the USOS and were more focused on breast resections, lymph node dissections, and port placements than on the traditional surgical rotation or USOS. CONCLUSIONS: The MDB incorporates multidisciplinary care into a unique, disease-specific, and educationally focused rotation. It is highly rated and affords a greater opportunity for DP than either the USOS or TCR. DP is strongly associated with mastery learning and this novel rotation structure could maximize intern education in the era of limited work hours.

Expanded criteria for carcinoid liver debulking: Maintaining survival and increasing the number of eligible patients.

BACKGROUND: Cytoreduction of carcinoid liver metastases typically aims for ≥ 90% debulking in patients without extrahepatic disease. Data on the impact of less-restrictive resection criteria and other clinical and tumor-specific factors on outcomes are limited. METHODS: Records of carcinoid patients undergoing liver debulking from 2007 to 2011 were reviewed. Debulking threshold was 70%, extrahepatic disease did not preclude cytoreduction, and positive margins were allowed. Kaplan-Meier liver progression-free (PFS) and disease-specific (DSS) survival were calculated and compared by log-rank analysis and statistical significance of differences in distributions of factors between patient groups was determined by chi-squared analysis. RESULTS: Fifty-two patients were identified. Complete resection of intrahepatic and extrahepatic gross disease was achieved in 12 patients. All primaries reviewed were low grade, but one third of patients had at least one intermediate-grade metastasis. Fifteen patients (29%) had liver progression; median PFS was 72 months. Five-year DSS was 90%, with all deaths from liver failure. Only age was an important prognostic factor for PFS and DSS. Five-year DSS for patients <50 years was 73% and was 97% for patients 50 or older (P = .03). CONCLUSION: The use of expanded criteria for debulking resulted in 90% 5-year DSS. Although younger age portends a poorer prognosis, the favorable PFS and DSS justify also using expanded criteria in this subgroup.