Fragmentation of Care in Patients with Peritoneal Metastases Undergoing Cytoreductive Surgery.

BACKGROUND: The delivery of multimodal treatment at a high-volume center is known to optimize the outcomes of gastrointestinal malignancies. However, patients undergoing cytoreductive surgery (CRS) for peritoneal metastases often must 'fragment' their surgical and systemic therapeutic care between different institutions. We hypothesized that this adversely affects outcomes. PATIENTS AND METHODS: Adults undergoing CRS for colorectal or appendiceal adenocarcinoma at our institution between 2016 and 2022 were identified retrospectively and grouped by care network: 'coordinated care' patients received exclusively in-network systemic therapy, while 'fragmented care' patients received some systemic therapy from outside-network providers. Factors associated with fragmented care were also ascertained. Overall survival (OS) from CRS and systemic therapy-related serious adverse events (SAEs) were compared across the groups. RESULTS: Among 85 (80%) patients, 47 (55%) had colorectal primaries and 51 (60%) received fragmented care. Greater travel distance [OR 1.01 (CI 1.00-1.02), p = 0.02] and educational status [OR 1.04 (CI 1.01-1.07), p = 0.01] were associated with receiving fragmented care. OS was comparable between patients who received fragmented and coordinated care in the colorectal [32.5 months versus 40.8 months, HR 0.95 (CI 0.43-2.10), p = 0.89] and appendiceal [31.0 months versus 27.4 months, HR 1.17 (CI 0.37-3.74), p = 0.55] subgroups. The frequency of SAEs (7.8% versus 17.6%, p = 0.19) was also similar. CONCLUSIONS: There were no significant differences in survival or SAEs based on the networks of systemic therapy delivery. This suggests that patients undergoing CRS at a high-volume center may safely receive systemic therapy at outside-network facilities with comparable outcomes.

Venous Thromboembolism in Peritoneal Mesothelioma: Uncovering the Hidden Risk.

INTRODUCTION: Venous thromboembolism (VTE) is a common complication in patients with abdominal malignancies. Despite known associations between pleural mesothelioma and increased VTE risk, the characteristics of VTE in patients with peritoneal mesothelioma (PeM) remain undescribed. METHODS: Patients treated for PeM were retrospectively identified from our institutional database. The frequency of VTE was assessed and logistic regression modeling was employed to assess VTE risk factors. The association between VTE and overall survival was also ascertained. Recommended thromboprophylaxis for patients who underwent surgery at our institution comprised a single preoperative dose of prophylactic anticoagulation, followed by daily dosing for four weeks postoperatively. RESULTS: Among 120 PeM patients, 26 (21.7%) experienced VTE, including 19/91 (20.9%) surgical patients, 4/23 (17.4%) patients who received systemic therapy, and 3/6 (50%) patients who underwent observation (p = 0.21). Most events were symptomatic (n = 16, 62%) and were attributable to pulmonary emboli (n = 16, 62%). The 90-day postoperative VTE rate was 4.4% (4/91), including 1 of 60 patients who underwent index surgical intervention at our institution and 3 patients with surgery elsewhere. A low serum albumin concentration was associated with VTE in non-surgical patients (odds ratio 0.12, confidence interval [CI] 0.02-0.72; p = 0.03). No significant difference in overall survival was observed between patients with and without VTE (median 46.0 months [CI 24.9-67.0] vs. 55.0 months [CI 27.5-82.5]; hazard ratio 0.98 [CI 0.54-1.81], p = 0.98). CONCLUSIONS: A high risk of VTE was observed in PeM patients, warranting suspicion throughout the disease trajectory. Postoperative VTE rates were within acceptable limits with 4-week thromboprophylaxis.

Role of Tumor-informed Personalized Circulating Tumor DNA Assay in Informing Recurrence in Patients With Peritoneal Metastases From Colorectal and High-grade Appendix Cancer Undergoing Curative-intent Surgery.

OBJECTIVE: To investigate the role of a personalized, tumor-informed circulating tumor DNA (ctDNA) assay in informing recurrence in patients with peritoneal metastases (PM) from colorectal (CRC) and high-grade appendix (HGA) cancer after curative cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). BACKGROUND: Over 50% of patients with CRC/HGA-PM recur after optimal CRS-HIPEC. The limited sensitivity of axial imaging and diagnostic biomarkers is a significant cause of delay in the detection of recurrence and initiation of further therapies. Plasma ctDNA has a promising role in monitoring response to treatment and/or recurrence after primary cancer resection. METHODS: Patients with CRC/HGA-PM who underwent curative CRS-HIPEC and serial postresection ctDNA assessments were included. Patients with rising postoperative ctDNA levels were compared with those with stable, undetectable ctDNA levels. Primary outcomes were the percentage of patients with recurrence and disease-free survival (DFS). Secondary outcomes were overall survival, ctDNA sensitivity, lead time, and performance of ctDNA compared with carcinoembryonic antigen. RESULTS: One hundred thirty serial postresection ctDNA assessments [median 4, interquartile range (IQR), 3 to 5] were performed in 33 patients (n = 13 CRC, n = 20 HGA) who underwent completeness of cytoreduction-0/1 CRS with a median follow-up of 13 months. Of the 19 patients with rising ctDNA levels, 90% recurred versus 21% in the stable ctDNA group (n = 14, < 0.001). Median DFS in the rising ctDNA cohort was 11 months (IQR, 6 to 12) and not reached in the stable ( P = 0.01). A rising ctDNA level was the most significant factor associated with DFS (hazard ratio: 3.67, 95% CI: 1.06-12.66, P = 0.03). The sensitivity and specificity of rising ctDNA levels in predicting recurrence were 85% and 84.6%, respectively. The median ctDNA lead time was 3 months (IQR, 1 to 4). Carcinoembryonic antigen was less sensitive (50%) than ctDNA. CONCLUSIONS: This study supports the clinical validity of serial ctDNA assessment as a strong prognostic biomarker in informing recurrence in patients with CRC/HGA-PM undergoing curative resection. It also holds promises for informing future clinical trial designs and further research.

Design and Implementation of a Learner-Centered Self-Paced Peritoneal Oncology Education Program.

BACKGROUND: Current educational programs for peritoneal surface malignancies (PSM) are unstructured and often target advanced learners. The authors describe the design and implementation of a structured, self-paced course at a high-volume PSM center. METHODS: In 2020, a learner-centered course was designed using the Canvas educational platform in consultation with the Center for Teaching at the University of Chicago. The course consisted of disease-site-specific modules, perioperative care pathways, in-built voluntary quizzes, and multimedia supplements for advanced learners. Trainees were provided access during the PSM service rotation, and engagement was compared across training levels by measuring the time spent online. RESULTS: Course design and management required 71 h between 2020 and 2022, with the majority of time spent in the design phase. During 3 years, 62 personnel (21 [34%] medical students, 28 [45%] residents, 8 [13%] staff, and 5 [8%] fellows) were assigned the course. The overall engagement rate was 83.9% (86% of medical students, 75% of residents, 100% of staff and fellows), and the median time spent online was 12.4 min/week (interquartile range [IQR], 2.1-53.0 min/week). Fourth-year medical students and clinical fellows spent more time online than other learners (73 min/week [IQR, 24.5-100 min/week] vs 13.3 min/week [IQR, 7.3-26.5 min/week]) (p = 0.001). CONCLUSIONS: The design and implementation of a PSM-specific course was feasible and sustainable using an online learning platform. Higher engagement was noted among invested learners. Non-technical factors for reduced engagement need to be ascertained further to improve the next iteration of this course.

Insurance Authorization Barriers in Patients Undergoing Cytoreductive Surgery and HIPEC.

BACKGROUND: Indications for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) exist across multiple histologies, but little data exist on the impact of insurance authorization on access to these therapies. Given the evolving role of CRS/HIPEC, we sought to characterize insurance approval and delays in patients undergoing these therapies. PATIENTS AND METHODS: A retrospective review was performed at a high-volume tertiary center of patients who received CRS/HIPEC from 2017 to 2021. Collected data included patient demographics, tumor histologic characteristics, insurance type, approval/denial history, and time to prior authorization approval. Descriptive statistics were performed. RESULTS: In total, 367 patients received CRS/HIPEC during the study period. They had a median age of 59 (IQR 49-67) years, 35% were male, and 76% were white. Of the patients requiring prior authorization, 14 of 104 (13%) patients were denied prior authorization and required appeal. Median time between authorization request and approval was 33 (IQR 28-36) days. These cases generated 410 insurance authorization requests, 94 (23%) of which were not initially approved and required appeal. The rate of upfront denial was 21.1% in patients with public insurance compared with 23.4% in patients with private insurance. Gastric cancer was the most common histology among denied cases (55%), followed by colorectal, appendiceal, and gynecologic malignancies. CONCLUSIONS: Despite the broadening indications for and data supporting CRS/HIPEC, a significant proportion of patients still face hurdles in attaining insurance approval and coverage for these therapies. Addressing barriers to insurance approval is imperative to decrease therapeutic delay and improve access to data-driven care.

Palliative Care and Characterization of Symptoms in Patients Undergoing Cytoreductive Surgery/Hyperthermic Intraperitoneal Chemotherapy.

INTRODUCTION: Palliative care for advanced cancer patients has been associated with improvements in symptom management and quality of life (QoL). Patients with peritoneal metastases undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) often report symptoms adversely affecting QoL. We characterized and compared symptoms elucidated by palliative care versus surgical providers in this setting. METHODS: CRS/HIPEC patients who saw both surgical oncology and palliative care providers from 2016 to 2020 at a tertiary care center were identified from a retrospective database. Documentation of QoL-associated symptoms in surgical oncology and palliative care visits was recorded and analyzed. RESULTS: A total of 118 patients were included in this study. The most common primary histologies were appendiceal (36.4%) and colorectal (28.8%). Symptoms most frequently reported by palliative care were pain (60.2%) and fatigue (54.2%). The median number of symptoms documented was three (2, 5) in palliative care notes and two (0, 3) in surgical oncology notes (P < 0.001). Palliative care providers documented most symptoms statistically more frequently than surgical oncology providers. CONCLUSIONS: Patients who underwent CRS/HIPEC experienced various QoL-associated symptoms. Palliative care providers elicited more symptoms than surgical oncology providers. Additional studies are needed to explore the impact on outcomes of perioperative palliative care in this challenging patient population.

Mutational profiles and prognostic impact in colorectal and high-grade appendiceal adenocarcinoma with peritoneal metastases.

BACKGROUND: Next-generation sequencing (NGS) personalizes cancer treatments. In this study, we analyze outcomes based on NGS testing for colorectal cancer (CRC) and high-grade appendiceal adenocarcinoma (HGA) with peritoneal metastases. METHODS: Retrospective review of genomic analyses and outcomes in patients with CRC or HGA with peritoneal metastases at a high-volume center from 2012 to 2019. RESULTS: Ninety-two patients (57 CRC, 35 HGA) were identified. Overall survival was longer for CRC (52.8 vs. 30.5 months, p = 0.03), though rates of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) were similar. Multiple genes were more frequently mutated in CRC, including KRAS (51% vs. 29%, p = 0.04), TP53 (47% vs. 20%, p < 0.01), and APC (46% vs. 6%, p < 0.01). For CRC, multivariate regression showed an increased hazard ratio (HR) with increasing peritoneal cancer index (1.06 [1.01-1.11], p = 0.02) and a decreased HR following CRS/HIPEC (0.30 [0.11-0.80], p = 0.02). PIK3CA mutation associated with significantly increased HR (3.62 [1.06-12.41], p = 0.04), though only in non-CRS/HIPEC patients. Multivariate analysis in the HGA group showed a benefit following CRS/HIPEC (0.18 [0.06-0.61], p = 0.01) and for mucinous disease (0.38 [0.15-0.96], p = 0.04), while there was an increased HR with TP53 mutation (6.89 [2.12-22.44], p < 0.01). CONCLUSION: CRC and HGA with peritoneal spread have distinct mutational profiles. PIK3CA and TP53 mutations are associated with survival for CRC or HGA with peritoneal metastases, respectively.

Surgical considerations and outcomes of minimally invasive approaches for gastric cancer resection.

Despite high mortality rates from gastric cancer, surgical management remains critical for curative potential. Optimal outcomes of gastric cancer resection depend on a multitude of variables, including the extent of resection, scope of lymphadenectomy, method of reconstruction, and potential for a minimally invasive approach. Laparoscopic gastrectomy, compared with open gastrectomy, has been analyzed in numerous randomized control trials. Generally, those trials demonstrated statistically similar postoperative complication rates, mortality, and oncologic outcomes between the two approaches. Although laparoscopic gastrectomy requires longer operative times, significant improvements in estimated blood loss, postoperative length of stay, and return of bowel function have been noted in patients who undergo laparoscopic gastrectomy. These short-term benefits, along with equivalent oncologic results, have influenced national guidelines in both Eastern and Western countries to recommend laparoscopy, especially for early stage disease. Although robotic gastrectomy has not been as widely validated in effective trials, studies have reported equivalent oncologic outcomes and similar or improved postoperative complication and recovery rates after robotic gastrectomy compared with open gastrectomy. Comparing the two minimally invasive gastrectomy approaches, robotic surgery was associated with improved estimated blood loss, incidence of pancreatic sequela, and lymph node harvests in some studies, whereas laparoscopy resulted in lower operative times and hospital costs. Ultimately, when applying outcomes from the literature to clinical patient care decisions, it is imperative to recognize these studies' range of inclusion criteria, delineating between patients originating from Eastern or Western countries, the use of neoadjuvant chemotherapy, the volume of surgeon experience, and the extent of gastrectomy, among others.

Overall health at diagnosis predicts the risk of complications within the first year after breast cancer diagnosis.

PURPOSE: Breast cancer patients with overall poor health are at a greater risk of both complications during treatment and mortality from competing causes. We sought to determine the association of pre-existing comorbidities on treatment-related complications and overall survival. METHODS: We identified women ages 40-90 years old from our institutional registry with stage I-II invasive breast cancer from 2005 to 2014. Recursive partitioning was used to stratify women based on pre-existing comorbidities as low, moderate, or high risk of treatment-associated complications. Cox proportional hazards model was constructed to estimate the association of risk with overall survival. RESULTS: 2077 women were studied. Mean age was 60 (IQR 51-68). Over half (54%) had ≥ 1 comorbid condition, and 29% experienced at least one adverse medical event within 1 year of diagnosis. Risk categories included low (no comorbidities or hypertension), moderate (combinations of comorbidities excluding congestive heart failure), and high (congestive heart failure in isolation or in combination with other conditions). High-risk women had a lower 10-year OS compared to moderate- or low-risk women (89% vs 90% vs 96%, log-rank p < 0.001). After adjustment, being at moderate (HR 2.20, 95% CI 1.30-3.72, p = 0.003) or high risk (HR 5.07, 95% CI 1.66-15.52, p = 0.004) of adverse sequelae was associated with reduced OS compared to those at low risk of these adverse medical events. CONCLUSIONS: Following breast cancer diagnosis, overall poor health was associated with a greater risk of mortality and complications within the first year of treatment, which was driven by a pre-existing diagnosis of congestive heart failure.

The Association of Extent of Axillary Surgery and Survival in Women with N2-3 Invasive Breast Cancer.

BACKGROUND: Although surgical management of the axilla for breast cancer continues to evolve, axillary lymphadenectomy remains the standard of care for women with advanced nodal disease. We sought to evaluate national patterns of care in axillary surgery, and its association with overall survival (OS) among women with N2-3 invasive breast cancer. METHODS: Women (18-90 years) with clinical N2-3 invasive breast cancer who underwent axillary surgery were identified from the National Cancer Data Base (NCDB) from 2004 to 2013. Axillary surgery was categorized as sentinel lymph node biopsy (SLNB, 1-5 nodes) or axillary lymph node dissection (ALND, ≥ 10 nodes). Patient and treatment characteristics, trends over time, and overall survival (OS) were compared by surgical treatment. RESULTS: Overall, 22,156 patients were identified. At diagnosis, 68.5% had cN2 and 31.5% had cN3 disease. Treatment included: lumpectomy (27%), mastectomy (73%), adjuvant chemotherapy (53.4%), neoadjuvant chemotherapy (NAC) (39.7%), radiation (74%), and endocrine therapy (54.4%). In total, 9.9% (n = 2190) underwent SLNB and 90.1% (n = 19,966) underwent ALND. Receipt of SLNB was associated with private insurance, grade 3 disease, invasive ductal cancer, NAC, and lumpectomy (all p < 0.001). After adjustment for known covariates, including chemotherapy use, ALND was associated with improved survival [hazard ratio (HR) 0.68, p < 0.001] and this effect was similar for N2 and N3 patients (axillary surgery × cN-stage interaction p = 0.29). CONCLUSIONS: Axillary lymphadenectomy was associated with improved survival in patients presenting with clinical N2-3 invasive breast cancer. Further studies, particularly in the neoadjuvant setting, are needed to identify breast cancer patients with advanced nodal disease who may safely avoid a lesser extent of axillary surgery.

Metaplastic Breast Cancer Treatment and Outcomes in 2500 Patients: A Retrospective Analysis of a National Oncology Database.

BACKGROUND: Metaplastic breast cancer (MBC) is characterized by chemoresistance and hematogenous spread. We sought to identify factors associated with improved MBC outcomes and increased likelihood of MBC diagnosis. METHODS: Women ≥ 18 years of age with stage I-III MBC and non-MBC diagnosed between 2010 and 2014 were identified in the National Cancer Data Base. Kaplan-Meier and multivariate Cox proportional hazards models were used to estimate associations with overall survival (OS). Multivariate logistic regression identified factors associated with MBC diagnosis. RESULTS: Overall, 2451 MBC and 568,057 non-MBC patients were included; 70.3% of MBC vs. 11.3% of non-MBC patients were triple negative (p < 0.001). Five-year OS was reduced among MBC vs. non-MBC patients for the entire cohort (72.7 vs. 87.5%) and among triple-negative patients (71.1 vs. 77.8%; both p < 0.001). In MBC, triple-negative (vs. luminal) subtype was not associated with worse OS (hazard ratio [HR] 1.16, 95% confidence interval [CI] 0.88-1.54, p = 0.28). Compared with non-MBC patients, MBC patients were more likely to receive mastectomy (59.0 vs. 44.9%), chemotherapy (74.1 vs. 43.1%), and axillary lymph node dissection (ALND; 35.2 vs. 32.2%, all p ≤ 0.001). MBC patients more frequently had negative ALND (pN0) than non-MBC patients (20.0 vs. 10.6%, p < 0.001). Among MBC patients, chemotherapy (HR 0.69, 95% CI 0.53-0.89, p = 0.004) and radiotherapy (HR 0.52, 95% CI 0.39-0.69, p < 0.001) were associated with improved survival, while ALND was associated with decreased survival (HR 1.37, 95% CI 1.06-1.77, p = 0.02). CONCLUSIONS: MBC patients had worse survival than non-MBC patients, independent of receptor status, suggesting that MBC may confer an additional survival disadvantage. Multimodal therapy was associated with improved outcomes, but ALND was not and may be overutilized in MBC.

Open versus laparoscopic portal lymphadenectomy in gallbladder cancer: is there a difference in lymph node yield?

BACKGROUND: Gallbladder cancer (GBC) is the most common biliary tract malignancy. Because it commonly metastasizes via lymphatics, portal lymphadenectomy should be included in oncologic resections. This study aimed to compare the oncologic equivalence of the laparoscopic versus open technique by evaluating lymph node (LN) yield. METHODS: The 2010-2012 National Cancer Data Base identified patients who underwent laparoscopic or open resection of GBC with dedicated lymphadenectomy. LN yield was compared by resection method. Variables associated with LN yield ≥3 were identified. RESULTS: Of 1524 patients identified, 52% were intended to undergo laparoscopic surgery, with 20% of these patients converted to open. Collection of ≥3 LNs following open resection (47%) was higher than for laparoscopic resection (34%), p < 0.001. Operations performed at high-volume (aOR:1.74, p < 0.001) and/or academic centers (aOR:1.70, p = 0.024) had superior LN yield. LN yield was not associated with overall survival (aHR:0.93, p = 0.493). CONCLUSIONS: In this analysis of national data, LN yield following laparoscopic resection for GBC was significantly lower than following open resection. Open resection is more frequently performed at academic centers, possibly to assure adequate oncologic resection. Enforcing consensus guidelines for lymphadenectomy in gallbladder cancer will optimize outcomes as minimally invasive approaches evolve.

Patient Age and Tumor Subtype Predict the Extent of Axillary Surgery Among Breast Cancer Patients Eligible for the American College of Surgeons Oncology Group Trial Z0011.

BACKGROUND: The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial established the safety of omitting axillary lymph node dissection (ALND) for early-stage breast cancer patients with limited nodal disease undergoing lumpectomy. We examined the extent of axillary surgery among women eligible for Z0011 based on patient age and tumor subtype. METHODS: Patients with cT1-2, cN0 breast cancers and one or two positive nodes diagnosed from 2009 to 2014 and treated with lumpectomy were identified in the National Cancer Data Base. Sentinel lymph node biopsy (SLNB) was defined as the removal of 1-5 nodes and ALND as the removal of 10 nodes or more. Tumor subtype was categorized as luminal, human epidermal growth factor 2-positive (HER2+), or triple-negative. Logistic regression was used to estimate the odds of receiving SLNB alone versus ALND. RESULTS: The inclusion criteria were met by 28,631 patients (21,029 SLNB-alone and 7602 ALND patients). Patients 70 years of age or older were more likely to undergo SLNB alone than ALND (27.0% vs 20.1%; p < 0.001). The radiation therapy use rate was 89.4% after SLNB alone and 89.7% after ALND. In the multivariate analysis, the uptake of Z0011 recommendations increased over time (2014 vs 2009: odds ratio [OR] 13.02; p < 0.001). Younger patients were less likely to undergo SLNB alone than older patients (age <40 vs ≥70: OR 0.59; p < 0.001). Patients with HER2+ (OR 0.89) or triple-negative disease (OR 0.79) (p < 0.001) were less likely to undergo SLNB alone than those with luminal subtypes. CONCLUSIONS: Among women potentially eligible for ACOSOG Z0011, the use of SLNB alone increased over time in all groups, but the extent of axillary surgery differed by patient age and tumor subtype.

Early Integrated Palliative Care Within a Surgical Oncology Clinic.

Importance: Advance directive (AD) designation is an important component of advance care planning (ACP) that helps align care with patient goals. However, it is underutilized in high-risk surgical patients with cancer, and multiple barriers contribute to the low AD designation rates in this population. Objective: To assess the association of early palliative care integration with changes in AD designation among patients with cancer who underwent surgery. Design, Setting, and Participants: This cohort study was a retrospective analysis of a prospectively maintained registry of adult patients who underwent elective surgery for advanced abdominal and soft tissue malignant tumors at a surgical oncology clinic in a comprehensive cancer center with expertise in regional therapeutics between June 2016 and May 2022, with a median (IQR) postoperative follow-up duration of 27 (15-43) months. Data analysis was conducted from December 2022 to April 2023. Exposure: Integration of ACP recommendations and early palliative care consultations into the surgical workflow in 2020 using electronic health records (EHR), preoperative checklists, and resident education. Main Outcomes and Measures: The primary outcomes were AD designation and documentation. Multivariable logistic regression was performed to assess factors associated with AD designation and documentation. Results: Among the 326 patients (median [IQR] age 59 [51-67] years; 189 female patients [58.0%]; 243 non-Hispanic White patients [77.9%]) who underwent surgery, 254 patients (77.9%) designated ADs. The designation rate increased from 72.0% (131 of 182 patients) before workflow integration to 85.4% (123 of 144 patients) after workflow integration in 2020 (P = .004). The AD documentation rate did not increase significantly after workflow integration in 2020 (48.9% [89 of 182] ADs documented vs 56.3% [81 of 144] ADs documented; P = .19). AD designation was associated with palliative care consultation (odds ratio [OR], 41.48; 95% CI, 9.59-179.43; P < .001), palliative-intent treatment (OR, 5.12; 95% CI, 1.32-19.89; P = .02), highest age quartile (OR, 3.79; 95% CI, 1.32-10.89; P = .01), and workflow integration (OR, 2.05; 95% CI, 1.01-4.18; P = .048). Patients who self-identified as a race or ethnicity other than non-Hispanic White were less likely to have designated ADs (OR, 0.36; 95% CI, 0.17-0.76; P = .008). AD documentation was associated with palliative care consulation (OR, 4.17; 95% CI, 2.57- 6.77; P < .001) and the highest age quartile (OR, 2.41; 95% CI, 1.21-4.79; P = .01). Conclusions and Relevance: An integrated ACP initiative was associated with increased AD designation rates among patients with advanced cancer who underwent surgery. These findings demonstrate the feasibility and importance of modifying clinical pathways, integrating EHR-based interventions, and cohabiting palliative care physicians in the surgical workflow for patients with advanced care.

A simple scoring system to estimate perioperative mortality following liver resection for primary liver malignancy-the Hepatectomy Risk Score (HeRS).

BACKGROUND: Selection of the optimal treatment modality for primary liver cancers remains complex, balancing patient condition, liver function, and extent of disease. In individuals with preserved liver function, liver resection remains the primary approach for treatment with curative intent but may be associated with significant mortality. The purpose of this study was to establish a simple scoring system based on Model for End-stage Liver Disease (MELD) and extent of resection to guide risk assessment for liver resections. METHODS: The 2005-2015 NSQIP database was queried for patients undergoing liver resection for primary liver malignancy. We first developed a model that incorporated the extent of resection (1 point for major hepatectomy) and a MELD-Na score category of low (MELD-Na =6, 1 point), medium (MELD-Na =7-10, 2 points) or high (MELD-Na >10, 3 points) with a score range of 1-4, called the Hepatic Resection Risk Score (HeRS). We tested the predictive value of this model on the dataset using logistic regression. We next developed an optimal multivariable model using backwards sequential selection of variables under logistic regression. We performed K-fold cross validation on both models. Receiver operating characteristics were plotted and the optimal sensitivity and specificity for each model were calculated to obtain positive and negative predictive values. RESULTS: A total of 4,510 patients were included. HeRS was associated with increased odds of 30-day mortality [HeRS =2: OR =3.23 (1.16-8.99), P=0.025; HeRS =3: OR =6.54 (2.39-17.90), P<0.001; HeRS =4: OR =13.69 (4.90-38.22), P<0.001]. The AUC for this model was 0.66. The AUC for the optimal multivariable model was higher at 0.76. Under K-fold cross validation, the positive predictive value (PPV) and negative predictive value (NPV) of these two models were similar at PPV =6.4% and NPV =97.7% for the HeRS only model and PPV =8.4% and NPV =98.1% for the optimal multivariable model. CONCLUSIONS: The HeRS offers a simple heuristic for estimating 30-day mortality after resection of primary liver malignancy. More complicated models offer better performance but at the expense of being more difficult to integrate into clinical practice.

Hippocampal memory processes are modulated by insulin and high-fat-induced insulin resistance.

Insulin regulates glucose uptake and storage in peripheral tissues, and has been shown to act within the hypothalamus to acutely regulate food intake and metabolism. The machinery for transduction of insulin signaling is also present in other brain areas, particularly in the hippocampus, but a physiological role for brain insulin outside the hypothalamus has not been established. Recent studies suggest that insulin may be able to modulate cognitive functions including memory. Here we report that local delivery of insulin to the rat hippocampus enhances spatial memory, in a PI-3-kinase dependent manner, and that intrahippocampal insulin also increases local glycolytic metabolism. Selective blockade of endogenous intrahippocampal insulin signaling impairs memory performance. Further, a rodent model of type 2 diabetes mellitus produced by a high-fat diet impairs basal cognitive function and attenuates both cognitive and metabolic responses to hippocampal insulin administration. Our data demonstrate that insulin is required for optimal hippocampal memory processing. Insulin resistance within the telencephalon may underlie the cognitive deficits commonly reported to accompany type 2 diabetes.

Breast cancer in Tanzanian, black American, and white American women: An assessment of prognostic and predictive features, including tumor infiltrating lymphocytes.

INTRODUCTION: Breast cancer is a major cause of morbidity and mortality for women in Sub-Saharan Africa and for black American women. There is evidence that the pathologic characteristics of breast cancers in both African women and black American women may differ from their counterparts of European ancestry. However, despite the great burden of disease, data on pathologic features of breast carcinoma in Sub-Saharan Africa is limited and often contradictory. This lack of information makes it difficult to prioritize resource use in efforts to improve breast cancer outcomes in the region. METHODS: We examined consecutive cases of breast cancer in Tanzanian women (n = 83), black American women (n = 120), and white American women (n = 120). Each case was assessed for tumor type, grade, mitotic count, ER and HER2 status, and tumor infiltrating lymphocyte involvement. RESULTS: The Tanzanian subjects were younger and had higher stage tumors than the subjects in either American group. Breast cancers in the Tanzanian and black American groups were more likely to be high grade (p = 0.008), to have a high mitotic rate (p<0.0001), and to be ER-negative (p<0.001) than the tumors in the white American group. Higher levels of tumor infiltrating lymphocyte involvement were seen among Tanzanian and black American subjects compared to white American subjects (p = 0.0001). Among all subjects, tumor infiltrating lymphocyte levels were higher in tumors with a high mitotic rate. Among Tanzanian and black American subjects, tumor infiltrating lymphocyte levels were higher in ER-negative tumors. These findings have implications for treatment priorities for breast cancer in Tanzania and other Sub-Saharan African countries.