Comprehensive value implications of surgeon volume for lung cancer surgery: Use of an analytic framework within a regional health system.

Objective: We used a framework to assess the value implications of thoracic surgeon operative volume within an 8-hospital health system. Methods: Surgical cases for non-small cell lung cancer were assessed from March 2015 to March 2021. High-volume (HV) surgeons performed >25 pulmonary resections annually. Metrics include length of stay, infection rates, 30-day readmission, in-hospital mortality, median 30-day charges and direct costs, and 3-year recurrence-free and overall survival. Multivariate regression-based propensity scores matched patients between groups. Metrics were graphed on radar charts to conceptualize total value. Results: All 638 lung resections were performed by 12 surgeons across 6 hospitals. Two HV surgeons performed 51% (n = 324) of operations, and 10 low-volume surgeons performed 49% (n = 314). Median follow-up was 28.8 months (14.0-42.3 months). Lobectomy was performed in 71% (n = 450) of cases. HV surgeons performed more segmentectomies (33% [n = 107] vs 3% [n = 8]; P < .001). Patients of HV surgeons had a lower length of stay (3 [2-4] vs 5 [3-7]; P < .001) and infection rates (0.6% [n = 1] vs 4% [n = 7]; P = .03). Low-volume and HV surgeons had similar 30-day readmission rates (14% [n = 23] vs 7% [n = 12]; P = .12), in-hospital mortality (0% [n = 0] vs 0.6% [n = 1]; P = .33), and oncologic outcomes; 3-year recurrence-free survival was 95% versus 91%; P = .44, and 3-year overall survival was 94% versus 90%; P = 0. Charges were reduced by 28%, and direct costs were reduced by 23% (both P < .001) in the HV cohort. Conclusions: HV surgeons provide comprehensive value across a health system. This multidomain framework can be used to help drive oncologic care decisions within a health system.

Time to Surgery and Colon Cancer Survival in the United States.

PURPOSE: Time to surgery (TTS) is of concern to patients diagnosed with cancer and their physicians. Controversy surrounds the impact of TTS on colon cancer survival. There are limited national data evaluating the association; thus, our aim was to estimate the overall survival (OS) impact from increasing TTS for patients with colon cancer. METHODS: Using the National Cancer Data Base (NCDB), we assessed OS as a function of time between diagnosis and surgery by evaluating intervals encompassing <7, 7 to 30, 31 to 60, 61 to 90, 91 to 120, and 121 to 180 days in length. All patients were diagnosed with nonmetastatic colon cancer and underwent surgery as initial treatment. Our main outcome was OS as a function of time between diagnosis and surgery, after adjusting for patient, demographic, and tumor-related factors using Cox regression models and propensity score-based weighting. RESULTS: A total of 514,103 patients diagnosed between 1998 and 2012 were included. Individuals having <7, 7 to 30, 31 to 60, 61 to 90, 91 to 120, and 121 to 180 days between diagnosis and surgery comprised 35.4%, 45%, 15.1%, 2.9%, 1%, and 0.6% of the patients, respectively. There was a steady increase in median TTS across the years. On multivariable analysis, TTS >30 days or within the first week independently increased mortality risk. There was a significant increase in mortality with TTS 31 to 60 [hazard ratio (HR) 1.13], 61 to 90 (HR 1.49), <7 (HR 1.56), 91 to 120 (HR 2.28), and 121 to 180 (HR 2.46) compared to surgery performed 7 to 30 days after diagnosis (P < 0.001). CONCLUSIONS: TTS is independently associated with OS and this represents a public health issue that should be addressed at a national level. Although time is required for evaluation before surgery, efforts to reduce TTS should be pursued.

500 Minimally Invasive Robotic Pancreatoduodenectomies: One Decade of Optimizing Performance.

OBJECTIVES: This study aims to present the outcomes of our decade-long experience of robotic pancreatoduodenectomy and provide insights into successful program implementation. BACKGROUND: Despite significant improvement in mortality over the past 30 years, morbidity following open pancreatoduodenectomy remains high. We implemented a minimally invasive pancreatic surgery program based on the robotic platform as one potential method of improving outcomes for this operation. METHODS: A retrospective review of a prospectively maintained institutional database was performed to identify patients who underwent robotic pancreatoduodenectomy (RPD) between 2008 and 2017 at the University of Pittsburgh. RESULTS: In total, 500 consecutive RPDs were included. Operative time, conversion to open, blood loss, and clinically relevant postoperative pancreatic fistula improved early in the experience and have remained low despite increasing complexity of case selection as reflected by increasing number of patients with pancreatic cancer, vascular resections, and higher Charlson Comorbidity scores (all P<0.05). Operating room time plateaued after 240 cases at a median time of 391 minutes (interquartile rang 340-477). Major complications (Clavien >2) occurred in less than 24%, clinically relevant postoperative pancreatic fistula in 7.8%, 30- and 90-day mortality were 1.4% and 3.1% respectively, and median length of stay was 8 days. Outcomes were not impacted by integration of trainees or expansion of selection criteria. CONCLUSIONS: Structured implementation of robotic pancreatoduodenectomy can be associated with excellent outcomes. In the largest series of RPD, we establish benchmarks for the surgical community to consider when adopting this approach.

Recommendations and guidelines for dentists using the basic erosive wear examination index (BEWE).

This paper explains how to screen tooth wear in general practice using the Basic Erosive Wear Examination (BEWE) index. It explains how stakeholders in the UK acknowledged the convenience of the BEWE and that it could be recorded at the same time as the Basic Periodontal Examination (BPE). The article contains examples of anterior and posterior tooth wear for each BEWE score to help dentists in their evaluation.

Fitbit step counts during inpatient recovery from cancer surgery as a predictor of readmission.

Background: Postoperative ambulation is encouraged to promote timely recovery but is rarely monitored objectively or examined as a predictor of clinical outcomes, despite growing availability of wearable devices that allow passive quantification and remote real-time monitoring of the number of steps taken during recovery. Purpose: To determine whether the number of steps taken during inpatient recovery predicts 30- and 60-day readmission risk after metastatic cancer surgery. Methods: Patients diagnosed with metastatic peritoneal cancer and scheduled for surgical resection were enrolled in this observational cohort study at their preoperative clinic visit. Fitbits were placed on patients' wrists upon transfer from the ICU following surgery and worn for the duration of their inpatient stay. Information about hospital readmission was extracted from electronic medical records. Results: Seventy-one patients participated in the study (mean age = 57.14, range = 31-80 years; 42% female; 51% diagnosed with appendiceal cancer). Mean steps per day were calculated for each participant over the entire inpatient recovery period (mean stay = 12.12 days, 4-37 days). Readmission within 30 and 60 days was medically indicated for 34% and 39% of patients, respectively. After statistically adjusting for age, body mass index, comorbidity, and length of postoperative stay, higher mean steps per day predicted lower 30-day and 60-day readmission risk. Conclusions: Higher Fitbit step counts during inpatient recovery predicted lower risk of 30- and 60-day readmission after surgery for metastatic peritoneal cancer. Results suggest that passively monitoring perioperative ambulation may identify patients at risk for readmission and highlight opportunities for behavioral intervention.

Depressive Symptoms in Patients Scheduled for Hyperthermic Intraperitoneal Chemotherapy With Cytoreductive Surgery: Prospective Associations With Morbidity and Mortality.

PURPOSE: The current study examined prospective relationships between preoperative depressive symptoms and short-term (30-day morbidity and readmission) and long-term (overall survival) outcomes after hyperthermic intraperitoneal chemotherapy with cytoreductive surgery (HIPEC + CS). METHODS: Ninety-eight patients scheduled for HIPEC + CS completed the Center for Epidemiologic Studies-Depression (CES-D) scale before surgery. Demographic and disease-specific factors and information about morbidity and readmission within 30 days after discharge were gathered from medical records. Survival was measured from date of surgery to death. RESULTS: Twenty-eight percent of patients had CES-D scores indicative of clinically significant depressive symptoms. Thirty-day morbidity occurred in 31.9% of patients and readmission in 22.2%. At the time of analysis (median follow-up of 49 months), 71.6% of patients were deceased, with median survival time of 11 months for those who died. After adjusting for relevant preoperative demographic and disease-specific factors, depressive symptoms were associated with greater odds of 30-day morbidity (n = 68; odds ratio, 5.50; 95% CI, 1.23 to 24.73; P = .03) and greater likelihood of 30-day readmission (n = 72; odds ratio, 5.92; 95% CI, 1.27 to 27.64; P = .02). Depressive symptoms were associated with shorter survival after adjustment for preoperative demographic and disease-specific factors (n = 87; hazard ratio, 1.88; 95% CI, 1.07 to 3.31; P = .03). This association was no longer significant when intraoperative/postoperative prognostic variables were added to the statistical model (n = 87; hazard ratio, 1.31; 95% CI, 0.72 to 2.37; P = .37). CONCLUSION: Patients with clinically significant levels of preoperative depressive symptoms are at risk for poor clinical outcomes after HIPEC + CS, including greater risk of 30-day morbidity and readmission. Further research is warranted to determine biobehavioral mechanisms and examine whether effective interventions targeting preoperative depressive symptoms can reduce postoperative risk in this patient population.

Targeting hypoxia-mediated mucin 2 production as a therapeutic strategy for mucinous tumors.

Excessive accumulation of mucin 2 (MUC2; a gel-forming secreted mucin) protein in the peritoneal cavity is the major cause of morbidity and mortality in pseudomyxoma peritonei (PMP). Hypoxia (hypoxia-inducible factor-1α; HIF-1α) has been shown to regulate the expression of similar mucins (eg, MUC5AC). We hypothesized that hypoxia (HIF-1α) drives MUC2 expression in PMP and is therefore a novel target to reduce mucinous tumor growth. The regulation of MUC2 by 2% hypoxia (HIF-1α) was evaluated in MUC2-secreting LS174T cells. The effect of BAY 87-2243, an inhibitor of HIF-1α, on MUC2 expression and mucinous tumor growth was evaluated in LS174T cells, PMP explant tissue, and in a unique intraperitoneal murine xenograft model of PMP. In vitro exposure of LS174T cells to hypoxia increased MUC2 messenger RNA (mRNA) and protein expression and increased HIF-1α binding to the MUC2 promoter. Hypoxia-mediated MUC2 protein overexpression was downregulated by transfected HIF-1α small interfering RNA (siRNA) compared with scrambled siRNA in LS174T cells. BAY 87-2243 inhibited hypoxia-induced MUC2 mRNA and protein expression in LS174T cells and PMP explant tissue. In a murine xenograft model of PMP, chronic oral therapy with BAY 87-2243 inhibited mucinous tumor growth and MUC2, HIF-1α expression in the tumor tissue. Our data suggest that hypoxia (HIF-1α) induces MUC2 promoter activity to increase MUC2 expression. HIF-1α inhibition decreases MUC2 production and mucinous tumor growth, providing a preclinical rationale for the use of HIF-1α inhibitors to treat patients with PMP.

Mitogen-activated protein kinase inhibition reduces mucin 2 production and mucinous tumor growth.

Excessive accumulation of mucin 2 (MUC2) protein (a gel-forming secreted mucin) within the peritoneal cavity is the major cause of morbidity and mortality in pseudomyxoma peritonei (PMP), a unique mucinous malignancy of the appendix. Mitogen-activated protein kinase (MAPK) signaling pathway is upregulated in PMP and has been shown to modulate MUC2 promoter activity. We hypothesized that targeted inhibition of the MAPK pathway would be a novel, effective, and safe therapeutic strategy to reduce MUC2 production and mucinous tumor growth. We tested RDEA119, a specific MEK1/2 (MAPK extracellular signal-regulated kinase [ERK] kinase) inhibitor, in MUC2-secreting LS174T cells, human PMP explant tissue, and in a unique intraperitoneal murine xenograft model of PMP. RDEA119 reduced ERK1/2 phosphorylation and inhibited MUC2 messenger RNA and protein expression in vitro. In the xenograft model, chronic oral therapy with RDEA119 inhibited mucinous tumor growth in an MAPK pathway-dependent manner and this translated into a significant improvement in survival. RDEA119 downregulated phosphorylated ERK1/2 and nuclear factor κB p65 protein signaling and reduced activating protein 1 (AP1) transcription factor binding to the MUC2 promoter in LS174T cells. This study provides a preclinical rationale for the use of MEK inhibitors to treat patients with PMP.

GNAS is frequently mutated in both low-grade and high-grade disseminated appendiceal mucinous neoplasms but does not affect survival.

We analyzed a series of 55 disseminated appendiceal mucinous neoplasms treated at our institution for GNAS and KRAS mutations in an attempt to correlate mutation status with clinicopathological findings and patient survival. GNAS mutations (p.R201H, c.602G>A and p.R201C, and c.602C>T) were identified in 17 (31%) of 55 of disseminated mucinous neoplasms and were found in 8 (35%) of 23 low-grade mucinous neoplasms, 7 (37%) of 19 high-grade mucinous adenocarcinomas lacking a signet ring cell component, and 2 (15%) of 13 high-grade mucinous adenocarcinomas with a signet ring cell component. All 7 mucinous adenocarcinomas composed of pure (>95%) signet ring cells harbored wild-type GNAS. There was no significant association between GNAS mutations and sex and age (both with P > .05) or between GNAS mutations and individual adverse histologic features including cytologic grade, destructive invasion, tumor cellularity, angiolymphatic invasion, perineural invasion, and signet ring cells (all with P > .05). KRAS mutations were identified in 22 (40%) of 55 disseminated mucinous neoplasms. GNAS-mutated disseminated appendiceal mucinous neoplasms more frequently harbored concurrent KRAS mutations compared with GNAS wild-type tumors (65% versus 29%, P = .018). GNAS mutations were not significantly associated with overall survival (both with P > .05). Only overall tumor grade was an independent predictor of overall survival in the multivariate analysis (P = .01). Our results indicate that GNAS mutations are frequently identified in both low-grade and high-grade disseminated appendiceal mucinous neoplasms indicating that GNAS mutation status cannot be used to distinguish between low-grade from high-grade appendiceal mucinous neoplasms.

Outcome analysis of a decade-long experience of isolated hepatic perfusion for unresectable liver metastases at a single institution.

OBJECTIVE: To evaluate outcomes of isolated hepatic perfusion (IHP) on isolated liver metastases (LMs). BACKGROUND: Isolated unresectable LMs are often the main determinant of overall survival (OS) for colorectal cancer (CRC) and other solid malignancies. We hypothesized that IHP can be performed safely and yield impressive responses for a variety of solid tumor pathology, using different perfusion agents. METHODS: Retrospective review of a prospectively collected database of patients undergoing IHP for unresectable solid tumor LM. RESULTS: Between 2003 and 2012, IHP was completed in 91 patients. Primary tumor pathology was CRC = 54, non-CRC = 37 (ocular/cutaneous melanoma = 32, cholangiocarcinoma = 3, appendiceal = 1, and breast = 1). IHP employed Melphalan (n = 69) (CRC = 32, non-CRC = 37), Oxaliplatin (n = 10) (CRC), or Oxaliplatin + 5FU (n = 12) (CRC). Hepatic arterial infusion (HAI) pumps were placed in all CRC patients. There were 3(3.3%) perioperative deaths. Response rates for CRC, melanoma, and cholangiocarcinoma were 68.2%, 57.1%, and 100% respectively. Response rates for CRC patients using 5FU + Oxaliplatin, Oxaliplatin, or Melphalan were 83.3%, 66.7%, and 60.9%, respectively. Median OS for the CRC patients (from IHP date) was 23 months (95% confidence interval: 15-28 months). On univariate analysis, receipt of HAI-FUDR (floxuridine) within 1 year of IHP was the only factor associated with improved OS (P = 0.043) in CRC patients. CONCLUSIONS: IHP results in excellent response rates for patients with unresectable liver metastasis from solid tumors. Improved local control for CRC patients undergoing IHP-HAI may improve survival.