A New Functional Threshold for Minimally Invasive Lobectomy.

OBJECTIVE: To assess the performance of a lower predicted postoperative (ppo) forced expiratory volume in 1 second (FEV1) or diffusion capacity of the lung for carbon monoxide (DLCO) (ppoFEV1/ppoDLCO) threshold to predict cardiopulmonary complications after minimally invasive surgery (MIS) lobectomy. SUMMARY BACKGROUND DATA: Although MIS is associated with better postoperative outcomes than open surgery, MIS uses risk-assessment algorithms developed for open surgery. Moreover, several different definitions of cardiopulmonary complications are used for assessment. METHODS: All patients who underwent MIS lobectomy for clinical stage I-II lung cancer from 2018 to 2022 at our institution were considered. The performance of a ppoFEV1/ppoDLCO threshold of <45% was compared against that of the current guideline threshold of <60%. Three different definitions of cardiopulmonary complications were compared: Society of Thoracic Surgeons (STS), European Society of Thoracic Surgeons (ESTS), and Berry et al. RESULTS: In 946 patients, the ppoFEV1/ppoDLCO threshold of <45% was associated with a higher proportion correctly classified (79% [95% CI, 76%-81%] vs. 65% [95% CI, 62%-68%]; P<0.001). The complication with the biggest difference in incidence between ppoFEV1/ppoDLCO of 45%-60% and >60% was prolonged air leak (33 [13%] vs. 34 [6%]; P<0.001). The predicted probability curves for cardiopulmonary complications were higher for the STS definition than for the ESTS or Berry definitions across ppoFEV1 and ppoDLCO values. CONCLUSIONS: The ppoFEV1/ppoDLCO threshold of <45% more accurately classified patients for cardiopulmonary complications after MIS lobectomy, emphasizing the need for updated risk-assessment guidelines for MIS lobectomy to optimize additional cardiopulmonary function evaluation.

Improved Preoperative Risk Assessment Tools Are Needed to Guide Informed Decision Making before Esophagectomy.

OBJECTIVE: We sought to evaluate the performance of 2 commonly used prediction models for postoperative morbidity in patients undergoing open and minimally invasive esophagectomy. SUMMARY BACKGROUND DATA: Patients undergoing esophagectomy have a high risk of postoperative complications. Accurate risk assessment in this cohort is important for informed decision-making. METHODS: We identified patients who underwent esophagectomy between January 2016 and June 2018 from our prospectively maintained database. Predicted morbidity was calculated using the American College of Surgeons National Surgical Quality Improvement Program Surgical Risk Calculator (SRC) and a 5-factor National Surgical Quality Improvement Programderived frailty index. Performance was evaluated using concordance index (C-index) and calibration curves. RESULTS: In total, 240 consecutive patients were included for analysis. Most patients (85%) underwent Ivor Lewis esophagectomy. The observed overall complication rate was 39%; the observed serious complication rate was 33%.The SRC did not identify risk of complications in the entire cohort (C-index, 0.553), patients undergoing open esophagectomy (C-index, 0.569), or patients undergoing minimally invasive esophagectomy (C-index, 0.542); calibration curves showed general underestimation. Discrimination of the SRC was lowest for reoperation (C-index, 0.533) and highest for discharge to a facility other than home (C-index, 0.728). Similarly, the frailty index had C-index of 0.513 for discriminating any complication, 0.523 for serious complication, and 0.559 for readmission. CONCLUSIONS: SRC and frailty index did not adequately predict complications after esophagectomy. Procedure-specific risk-assessment tools are needed to guide shared patient-physician decision-making in this high-risk population.

Exposure to Polybrominated Diphenyl Ether Flame Retardants Causes Deoxyribonucleic Acid Damage in Human Thyroid Cells In Vitro.

INTRODUCTION: The incidence of papillary thyroid cancer (PTC) in the United States has tripled in the past 30 y. Polybrominated diphenyl ethers (PBDEs) are flame retardants that were ubiquitously used over that time period, and exposure to PBDEs has been associated with PTC prevalence. They are potential carcinogens via their induction of reactive oxygen species (ROS) formation and resultant deoxyribonucleic acid (DNA) damage. We sought to determine the effects of PBDE and tris(2-chloroethyl) phosphate (TCEP), another flame retardant implicated in PTC incidence, on thyrocytes in vitro and measure PBDE levels in human thyroid tissue to determine their carcinogenic potential. METHODS: Nthy-Ori, an immortalized benign human thyroid follicular cell line was used as a model of normal human thyroid. MTT assays were used to measure cell viability after exposure to PBDEs and TCEP. ROS levels and double-stranded and single-stranded DNA breaks were measured to determine genotoxicity. DNA damage response protein levels were measured with immunoblotting. RESULTS: Exposure to 20µM PBDE or TCEP for 48 h had minimal effects on thyrocyte viability. There was no significant increase in intracellular ROS up to 6 h following PBDE or TCEP exposure in thyrocytes; however, cells exposed to PBDE 47 showed evidence of DNA single-stranded and double-stranded breaks. There was a dose-dependent increase in γH2AX levels following exposure to PBDEs 47 and 209 in Nthy-Ori cells but not with TCEP treatment. CONCLUSIONS: PBDE 47 and 209 demonstrated genotoxicity but not cytotoxicity in follicular thyrocytes in vitro. Therefore, PBDE 47 and 209 may be carcinogenic in human thyroid cells.

Frailty is More Predictive than Age for Complications After Thyroidectomy for Multinodular Goiter.

BACKGROUND: Risks of thyroidectomy for multinodular goiter (MNG) in older and frail patients are unclear, particularly regarding hematoma and recurrent laryngeal nerve (RLN) palsy. METHODS: MNG patients undergoing total thyroidectomy were reviewed in the ACS-NSQIP procedure-targeted database (2016-2017). Outcomes were analyzed between adult (age <65), older-adult (age ≥65 and <80), and oldest-old (age ≥80) patients. Five-factor modified frailty index (mFI-5) was calculated based on functional status, diabetes, COPD, CHF, and hypertension, and used in comparative analyses. RESULTS: A total of 2189 adult, 635 older-adult, and 59 oldest-old patients were included. Compared to adult patients, older-adult and oldest-old patients had higher mFI-5 ≥0.4 rates (14% vs. 22% vs. 31%, respectively, p < 0.001). The overall complication rate was 17.0% and similar between groups; however, oldest-old patients had higher rates of surgical site infection (3.4% vs. 0.3% vs. 0.4%), pneumonia (5.1% vs. 0.3% vs. 0.2%), and readmission (10.2% vs. 2.4% vs. 2.6%) compared to older-adult and adult patients, respectively (p < 0.05). On multivariable analyses of thyroidectomy-specific complications, mFI-5 ≥0.4 (OR 2.5, 95%-CI 1.4-4.4) and bleeding disorder (OR 4.6, 95%-CI 1.3-16.3) were predictive of hematoma, whereas vessel-sealant device usage (OR 0.4, 95%-CI 0.3-0.7) was protective. mFI-5 ≥ 0.4 (OR 1.5, 95%-CI 1.1-2.2), bleeding disorder (OR 2.8, 95%-CI 1.04-7.8), parathyroid autotransplantation (OR 1.7, 95%-CI 1.2-2.6), and prolonged operative time (OR 1.4, 95%-CI 1.02-1.8) were predictive of RLN palsy. Age was not a significant predictor of hematoma or RLN palsy. CONCLUSIONS: Patients ≥80 years old are at increased risk for systemic complications and readmission after thyroidectomy for MNG. Frailty index better risk-stratifies patients than age for thyroidectomy-specific complications.

Laparoscopic Adrenalectomy Has the Same Operative Risk as Routine Laparoscopic Cholecystectomy.

BACKGROUND: Laparoscopic adrenalectomy (LA) is the treatment of choice for aldosteronomas and other adrenal tumors. Despite evidence that surgical cure of aldosteronomas is superior to medical treatment, reluctance remains to refer patients for LA. Here we compared the safety profile of LA to laparoscopic cholecystectomy (LC), a commonly performed laparoscopic procedure. MATERIALS AND METHODS: Patients undergoing LA or LC from 2012 to 2015 were selected from the National Surgical Quality Improvement Program. Patients who had an LA for an adrenal adenoma or aldosteronoma were compared to those who had LC for biliary colic or cholelithiasis. Multivariable logistic regressions were used to analyze postoperative outcomes between the two groups, controlling for patient factors. RESULTS: A total of 19,315 patients met inclusion criteria (n = 1458 LA, n = 17,857 LC). Patients undergoing an LA were older (median 53 versus 46 y old, P < 0.001), with a higher rate of American Society of Anesthesiologists score ≥3 (65.6% versus 25.0%, P < 0.001) and modified frailty index score ≥ 1 (78.5% versus 33.6%, P < 0.001). Overall mortality was 0.1% with no difference between the two cohorts (P = 0.426). Incidence of at least one postoperative complication was higher in the LA cohort (3.6% versus 2.2%, P < 0.001). However, when adjusting for demographics, comorbidities, and operative time, adrenalectomy was not associated with an increased risk of postoperative complications (OR 0.83 (0.6-1.2), P = 0.268). CONCLUSIONS: After comparing postoperative outcomes between patients undergoing LA and LC, operation type was not independently associated with an increased incidence of complications. Therefore, physicians should consider LA as having a similar overall risk profile to LC when deciding whether to refer patients to surgery.

Predicting Survival and Response to Treatment in Gastroesophageal Neuroendocrine Tumors: An Analysis of the National Cancer Database.

BACKGROUND: Neuroendocrine tumors (NETs) of the esophagus and stomach are rare neoplasms with variable behavior. We aim to describe their epidemiology and response to treatment. METHODS: NETs of the stomach and the esophagus were selected from the National Cancer Database (2004-2013) and classified by location. Survival analyses were performed with respect to tumor characteristics and treatment variables. RESULTS: NETs of the stomach (n = 2700; 92.8%) and esophagus (n = 210, 7.2%) were identified. Gastric cardia NETs had demographics and behavior similar to esophageal tumors and were associated with worse overall survival than NETs of the noncardia stomach independent of grade (p < 0.001). Poorly differentiated histology [hazard ratio (HR) 4.14, 95% confidence interval (CI) 2.26-7.57; p < 0.001] and distant metastases (HR 3.28, 95% CI 1.94-5.56; p < 0.001) were the greatest independent predictors of survival. For patients with poorly differentiated NETs, surgery was the only treatment to have benefit on overall survival (HR 0.38, 95% CI 0.27-0.54; p < 0.001) regardless of extent of disease. There was no additional benefit to adjuvant chemotherapy or radiation in patients undergoing resection (p = 0.39), even for patients with lymph node metastases (surgery alone versus surgery plus adjuvant therapy, p = 0.46), distant metastases (p = 0.19), or positive margins (p = 0.33). CONCLUSIONS: Esophageal and gastric cardia NETs have worse survival than those of the noncardia stomach. Surgery offers the only survival benefit for poorly differentiated tumors, with no additional survival advantage to adjuvant chemotherapy or radiation.

CHL1 expression differentiates Hürthle cell carcinoma from benign Hürthle cell nodules.

BACKGROUND AND OBJECTIVES: Hürthle cell carcinoma (HCC) is an unusual and relatively rare type of differentiated thyroid cancer. Currently, cytologic analysis of fine-needle aspiration biopsy is limited in distinguishing benign Hürthle cell neoplasms from malignant ones. The aim of this study was to determine whether differences in the expression of specific genes could differentiate HCC from benign Hürthle cell nodules by evaluating differential gene expression in Hürthle cell disease. METHODS: Eighteen benign Hürthle cell nodules and seven HCC samples were analyzed by whole-transcriptome sequencing. Bioinformatics analysis was carried out to identify candidate differentially expressed genes. Expression of these candidate genes was re-examined by quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was quantified by immunohistochemistry. RESULTS: Close homolog of L1 (CHL1) was identified as overexpressed in HCC. CHL1 was found to have greater than 15-fold higher expression in fragments per kilobase million in HCC compared with benign Hurthle cell tumors. This was confirmed by qRT-PCR. Moreover, the immunoreactivity score of the CHL1 protein was significantly higher in HCC compared with benign Hürthle cell nodules. CONCLUSIONS: CHL1 expression may represent a novel and useful prognostic biomarker to distinguish HCC from benign Hürthle cell disease.

Aortic Angulation Does Not Impact Outcomes in Self-Expandable or Balloon-Expandable Transcatheter Aortic Valve Replacement.

OBJECTIVES: The role of aortic angulation in attenuating procedural success in balloon-expandable (BE) and self-expandable (SE) transcatheter aortic valve replacement (TAVR) has been controversial. METHODS: We retrospectively assessed patients undergoing SE and BE TAVR who had an aortic angle measured on multidetector computed tomography at a single tertiary referral center. The primary outcome was device success, measured per the Valve Academic Research Consortium-2 criteria. Clinical outcomes at 30 days (including mortality) were also assessed. RESULTS: A total of 251 patients were identified; 182 patients received a BE valve and 69 patients an SE valve. The median aortic angle was 46.8° (range 24.4-70°) in the BE group and 43.3° (range 20-71°) in the SE group. In multivariate logistic regression analysis, aortic angulation did not affect device success. Mortality at 30 days and 12 months and postprocedural clinical outcomes were similarly not associated with aortic angulation. CONCLUSION: In this cohort of patients undergoing BE and SE TAVR over a wide range of aortic angles, we found no associations between angle and device success or any other clinical metrics. Increased aortic angulation does not adversely affect outcomes in BE or SE TAVR.

Perioperative outcomes and anesthetic considerations of robotic bariatric surgery in a propensity-matched cohort of super obese and super-super obese patients.

BACKGROUND: The use of the robotic platform has not been well established in patients with super obesity (SO; body mass index, BMI ≥ 50) and super-super obesity (SSO, BMI ≥ 60). We aimed to determine safety and feasibility of robotic bariatric surgery in this cohort. METHODS: Review of a prospectively maintained database was performed of consecutive patients undergoing robotic bariatric surgery between 2015 and 2017. Propensity score analysis with 1:2 nearest neighbor matching was performed to control for baseline characteristics and procedure type. RESULTS: A propensity-matched cohort of 47 SO patients (median BMI 55.3, range 50.1-92.5) and 94 morbidly obese (MO; median BMI 41.8, range 35.1-48.8) patients were analyzed. After matching, there were no difference in baseline characteristics including age, American Society of Anesthesiologists (ASA) score, or preoperative comorbidities. Most patients in each group underwent sleeve gastrectomy (81% of SO patients versus 76% of MO patients) or Roux-en-Y gastric bypass (13% vs. 18%, respectively), p = 0.66. There were no differences in operative time, intraoperative complications, postoperative complications, or re-admissions between groups. Length of stay was slightly longer in the MO group (2.2 days, IQR 1.8-3.2 vs. 1.8 days, IQR 1.2-2.7; p = 0.01). A subset of SSO patients (n = 11, median BMI 67, range 60-92) was analyzed; there was no increase in operation time, and zero intraoperative complications, conversions to open, or postoperative complications in this subset. CONCLUSIONS: Robotic bariatric surgery can safely be performed on patients with SO or SSO with low perioperative morbidity and no increase in operating time.

Robotic Reoperative Anti-reflux Surgery: Low Perioperative Morbidity and High Symptom Resolution.

BACKGROUND: Laparoscopic reoperative anti-reflux surgery (ARS) has a significantly higher morbidity than laparoscopic primary ARS; however, it is not known whether the same pattern exists within the robotic approach. We aimed to evaluate the safety and efficacy of robotic reoperative ARS in comparison with primary robotic ARS. METHODS: A retrospective review of patients undergoing primary or reoperative robotic ARS at a tertiary referral center between 2012 and 2017 was performed. Perioperative outcomes and long-term symptom resolution were evaluated. RESULTS: A total of 200 patients were included (38 reoperative and 162 primary ARS). Baseline characteristics were comparable across groups. Seven (18.4%) of the reoperative patients had two or more prior foregut operations. Patients in the reoperative group had a longer operative time (226 vs. 180 min, p < 0.001). There were no conversions to open technique, and one patient in the reoperative group (2.6%) had an intraoperative perforation. Twenty of the 38 reoperative patients (52.6%) were discharged within 24 h as compared to 109/162 primary patients (64.9%) (p = 0.09). The readmission rate and postoperative complication rates were 6 and 3%, respectively, and did not differ between groups. At a mean follow-up of 1 year, complete or partial resolution of preoperative symptoms was achieved in 97% of primary patients and 100% of reoperative patients (p = 0.4). CONCLUSION: The robotic approach allows for minimal morbidity, short length of stay, and excellent functional outcomes in patients undergoing reoperative ARS when compared to patients undergoing primary ARS.

Laparoscopic Appendectomy: Minimally Invasive Surgery Training Improves Outcomes in Basic Laparoscopic Procedures.

BACKGROUND: To determine whether minimally invasive surgery (MIS) training improves outcomes in laparoscopic appendectomy, a procedure that is commonly performed in general surgery training. METHODS: Retrospective review was conducted of all patients undergoing laparoscopic appendectomy for suspected acute appendicitis between 2014 and 2015 at a single-center, tertiary-care academic institution. Patients operated on by MIS-trained surgeons (MIS group) were compared to those operated on by general surgeons (GS group). Single-incision and multiport laparoscopic appendectomies were included; open approach, known malignancy, and interval appendectomies were excluded. RESULTS: A total of 507 patients were included in the study: 181 patients in the MIS group and 326 in the GS group. There were no differences in patient demographics or medical comorbidities between groups and most patients were ASA class 1 or 2. Patients operated on by MIS-trained surgeons had significantly shorter operative time (43 min, IQR 32-60 vs. 58 min, IQR 44-81; p < 0.001) and fewer intra-operative adverse events (0/181 vs. 8/326, 2.5%; p = 0.03). There was no difference in number of postoperative adverse events between groups (6/181, 3.3% vs. 21/326, 6.4%; p = 0.13). In the MIS group, subgroup analysis of single-incision versus multiport appendectomy showed no differences in intra-operative or postoperative adverse events. On multivariable linear regression, lack of MIS training and traditional multiport approach had the greatest effects on prolonging operative time (11.2 and 12.8 min, respectively; p = 0.001). CONCLUSIONS: MIS fellowship improves operative metrics and patient outcomes even in basic laparoscopy.

Less is More: The Impact of Multidisciplinary Thyroid Conference on the Treatment of Well-Differentiated Thyroid Carcinoma.

BACKGROUND: In 2006, a multidisciplinary thyroid conference (MDTC) was implemented to better plan management of thyroid cancer patients at our institution. This study assessed the clinical impact of a MDTC on radioactive iodine (RAI) treatment patterns. METHODS: A prospective database (2003-2014) collected patient and tumor characteristics, RAI doses, and tumor recurrences. Patients treated with total thyroidectomy for differentiated thyroid carcinoma ≥1 cm were stratified based on American Thyroid Association (ATA) risk classification. RAI regimens were compared before initiation of MDTC (2003-2005, n = 88), after establishment of MDTC (2007-2009, n = 95), and after the release of 2009 ATA guidelines (2011-2014, n = 181). RAI doses were defined as low (≤75 mCi), intermediate (76-150 mCi), and high (>150 mCi). RESULTS: There was a significant decrease in the number of patients who received high-dose RAI after implementation of MDTC compared to before initiation of MDTC in the intermediate and high-risk patient groups (p = 0.04 and p < 0.01) without an associated increase in tumor recurrence (11 vs. 7%, p = 0.74). On multivariable analysis, presentation of a patient at MDTC was a negative predictor for receiving high-dose RAI (p = 0.002). As might be expected, there was also a significant decrease in use of RAI after the 2009 ATA guidelines were issued compared to after implementation of MDTC (p < 0.01). CONCLUSION: In conjunction with implementation of a thyroid malignancy multidisciplinary conference, we observed significantly decreased postoperative dosing of RAI without increased tumor recurrence. The 2009 ATA guidelines were associated with a further decrease in RAI administration. Treatment for patients with thyroid carcinoma is optimized by a multidisciplinary approach.

The Impact of Nodal Dissection on Staging in Adrenocortical Carcinoma.

BACKGROUND: The role of lymphadenectomy in adrenocortical carcinoma (ACC) is controversial, and formal lymph node (LN) dissection is not routine. We sought to determine the minimum number of LNs that must be examined to accurately identify a patient as node negative. METHODS: The National Cancer Database was used to identify patients diagnosed with ACC from 2004 to 2013 who underwent surgical resection. Patients with distant metastases, multivisceral resection, or missing surgical or lymphadenectomy data were excluded. The primary outcome was overall survival (OS). RESULTS: LNs were identified on histopathology in 156 patients. Of these, 35 (22%) had at least one positive LN. Positive LNs were associated with positive surgical margins (odds ratio [OR] 5.80, p = 0.002) and increasing LN yield (OR 1.06, p = 0.02). Overall, on Cox regression analysis, LN positivity (hazard ratio [HR] 3.02, p < 0.001) and positive surgical margins (HR 2.06, p = 0.048) independently predicted poor OS after controlling for other factors that may influence survival. LN(-) disease in patients with one to three LNs examined had poorer overall survival compared with when at least four LNs were examined (p = 0.02). None of the other patient, tumor, and treatment variables had any impact on OS of the LN(-) cohort. The likelihood of identifying nodal involvement was higher on examination of at least four LNs compared with examination of one to three LNs (30 vs. 16%, p = 0.03). CONCLUSIONS: LN positivity in ACC tumors independently predicts worse 5-year OS and a minimum of four LNs may be required to accurately determine LN negativity.

The impact of the robotic platform on assistant variability in complex gastrointestinal surgery.

BACKGROUND: Nissen fundoplication is considered an advanced minimally invasive procedure whether performed laparoscopically or robotically. In laparoscopic surgery, it is evident that assistant skill level impacts operative times. However, the robotic platform allows improved surgeon autonomy. We aimed to determine the impact of assistant training level on operative times in robotic Nissen fundoplication (RNF) and laparoscopic Nissen fundoplication (LNF). METHODS: A prospectively maintained Nissen database (2011-2016) from a single academic institution was utilized to collect patient characteristics, operative times, length of stay, intraoperative complications, postoperative complications, readmission rate, and assistant training level. Assistants were either postgraduate year-3 surgery residents defined as junior-level assistants or a minimally invasive surgery (MIS) fellow defined as senior-level assistants. RESULTS: There were 105 patients included in our analyses. When comparing postgraduate year-3 residents to MIS fellows performing LNF, the median operative time was significantly decreased when senior-level assistants were present in the LNF group, 85 (75-103) versus 129 (74-269) min, P = 0.02. In comparison, median operative times in the RNF group were independent of the assistant's level of training, 154 (71-300) versus 158 (101-215) min, P = 0.34. There were no significant differences in outcomes between the junior- and senior-level assistant cohorts for estimated blood loss, length of stay, postoperative complications, and 30-d readmission rates in either the LNF or RNF group. CONCLUSIONS: Assistant training level impacted operative time for LNF but not RNF. These differences are most likely attributed to increased autonomy of the operating surgeon afforded by the robotic platform reducing assistant variability.

Minimally Invasive Ivor Lewis Esophagectomy.

Minimally invasive Ivor Lewis esophagectomy is a technically demanding operation that requires an experienced surgeon, assistant, and anesthesiologist. The preoperative workup should focus on the extent of disease and extent of resection required, as well as the cardiopulmonary fitness of the patient. Surgical outcomes show decreased postoperative pain, decreased morbidity largely due to a reduction in respiratory complications, and decreased length of stay. Quality metrics and 5-year overall survival are equivalent to traditional open esophagectomy.

Late Recurrence of Completely Resected Stage I-IIIA Lung Adenocarcinoma.

OBJECTIVE: Research into the risk factors associated with late recurrence (>2 years after surgery) of lung adenocarcinoma (LUAD) is limited. We investigated the incidence of and clinicopathologic and genomic features associated with late recurrence of resected stage I-IIIA LUAD. METHODS: We performed a retrospective analysis of patients with completely resected pathologic stage I-IIIA LUAD (2010-2019). Patients with a history of lung cancer, neoadjuvant therapy, or mucinous or noninvasive LUAD, or with follow-up of <2 years were excluded. Cox and logistic regression modeling were used to compare clinicopathologic variables among patients with no, early (≤2 years), and late recurrence. Comparisons of genomic mutations were corrected for multiple testing. RESULTS: Of the 2349 patients included, 537 developed a recurrence during follow-up. Most recurrences (55% [297/537]) occurred early; 45% (240/537) occurred late. A larger proportion of late recurrences than early recurrences were locoregional (37% vs. 29%; p=0.047). Patients with late recurrence had more aggressive pathologic features (IASLC grade 2 and 3, lymphovascular invasion, visceral pleural invasion) and higher stage than patients without recurrence. Pathologic features were similar between patients with early and late recurrence, except stage IIIA disease was more common in the early cohort. No genomic mutations were associated with late recurrence. CONCLUSIONS: Late recurrence of LUAD following resection is more common than previously reported. Patients without disease >2 years after surgery who had aggressive pathologic features at the time of resection have an elevated risk of recurrence and may benefit from more-aggressive follow-up.

Immunotherapy for Resectable Locally Advanced Esophageal Carcinoma.

BACKGROUND: The current standard of care for locally advanced esophageal and gastroesophageal junction (GEJ) cancers includes neoadjuvant chemoradiotherapy or perioperative chemotherapy with surgical resection; however, disease-free survival in these patients remains poor. Immune checkpoint inhibitors (ICIs) are approved for adjuvant treatment of locally advanced esophageal and GEJ cancers, but their benefit in the perioperative and neoadjuvant settings remains under investigation. METHODS: We used the PubMed online database to conduct a literature search to identify studies that investigated immunotherapy for locally advanced esophageal and GEJ carcinoma. A review of ClinicalTrials.gov yielded a list of ongoing trials. RESULTS: Adjuvant nivolumab for residual disease after neoadjuvant chemoradiotherapy and surgery is the only approved immunotherapy regimen for locally advanced esophageal cancer. Early-phase trials investigating the addition of neoadjuvant or perioperative ICIs to standard-of-care multimodality approaches have observed pathologic complete response rates as high as 60%. Response rates are highest for ICIs plus chemoradiotherapy for esophageal squamous cell carcinoma and dual checkpoint inhibition in mismatch repair-deficient adenocarcinomas. Safety profiles are acceptable, with a pooled adverse event rate of 27%. Surgical morbidity and mortality with immunotherapy are similar to historical controls with no immunotherapy, and R0 resection rates are high. When reported, disease-free survival among patients treated with perioperative immunotherapy is promising. CONCLUSIONS: Outside of clinical trials, immunotherapy for resectable esophageal carcinoma is limited to the adjuvant setting. Phase III trials investigating neoadjuvant and perioperative immunotherapy are now underway and will provide much-needed data on survival that may ultimately lead to practice-changing recommendations.

Activation of the JAK/STAT Pathway Leads to BRAF Inhibitor Resistance in BRAFV600E Positive Thyroid Carcinoma.

A subset of thyroid cancers, recurrent differentiated thyroid cancers and anaplastic thyroid cancer (ATC), are difficult to treat by thyroidectomy and systemic therapy. A common mutation in thyroid cancer, BRAFV600E, has targetable treatment options; however, the results have been disappointing in thyroid cancers compared with BRAFV600E melanoma, as thyroid cancers quickly become resistant to BRAFV600E inhibitor (BRAFi). Here, we studied the molecular pathway that is induced in BRAFV600E thyroid cancer cells and patient-derived tumor samples in response to BRAFi, vemurafenib, using RNA-sequencing and molecular analysis. Both inducible response to BRAFi and acquired BRAFi resistance in BRAFV600E thyroid cancer cells showed significant activation of the JAK/STAT pathway. Functional analyses revealed that the combination of BRAFi and inhibitors of JAK/STAT pathway controlled BRAFV600E thyroid cancer cell growth. The Cancer Genome Atlas data analysis demonstrated that potent activation of the JAK/STAT signaling was associated with shorter recurrence rate in patients with differentiated thyroid cancer. Analysis of tumor RNA expression in patients with poorly differentiated thyroid cancer and ATC also support that enhanced activity of JAK/STAT signaling pathway is correlated with worse prognosis. Our study demonstrates that JAK/STAT pathway is activated as BRAFV600E thyroid cancer cells develop resistance to BRAFi and that this pathway is a potential target for anticancer activity and to overcome drug resistance that commonly develops to treatment with BRAFi in thyroid cancer. IMPLICATIONS: Dual inhibition of BRAF and JAK/STAT signaling pathway is a potential therapeutic treatment for anticancer activity and to overcome drug resistance to BRAFi in thyroid cancer.

Implementing a High-Value Care Discharge Protocol in Patients Undergoing CABG Reduces Readmission.

BACKGROUND: Readmission after coronary artery bypass grafting (CABG) is associated with adverse outcomes and increased cost. We evaluated the impact of a high-value care discharge protocol on readmission, length of stay (LOS), and discharge destination in patients undergoing isolated CABG. METHODS: In 2016, a comprehensive, patient-centered discharge protocol was implemented. A nurse practitioner was the fulcrum of this program, which focused on improving health literacy, disease management, and rigorous follow-up. All patients undergoing isolated CABG between 2012 and 2019 were retrospectively analyzed with regard to 30-day readmission, LOS, and discharge disposition. Differences were analyzed by Mann-Whitney, chi-square, and t tests. Analyses were repeated using propensity matching. RESULTS: A total of 910 consecutive patients undergoing isolated CABG were included in the analyses: 353 preprotocol and 557 postprotocol. Preprotocol patients had a readmission rate of 14.4% (n = 51), compared with 6.8% (n = 38) in the postprotocol patients (P < .001). Median postoperative LOS before implementation was 6 (interquartile range, 5-8) days compared with 5 (interquartile range, 4-6) days postimplementation (P < .001). Postimplementation, a higher proportion of patients were discharged to home compared with a skilled nursing facility (82.7% [n = 461] vs 73.9% [n = 261]; P = .002). After propensity matching, 298 well-balanced patients were included for analysis and these significant reductions in LOS, readmission, and discharge destination persisted. CONCLUSIONS: Implementation of a new discharge protocol was significantly associated with reduced readmission and LOS, along with higher rates of discharge to home in isolated CABG patients. Importantly, the results were sustainable and did not require additional resources, delivering high-value care.