Bioinspired Materials for Wearable Devices and Point-of-Care Testing of Cancer.

Wearable, point-of-care diagnostics, and biosensors are on the verge of bringing transformative changes in detection, management, and treatment of cancer. Bioinspired materials with new forms and functions have frequently been used, in both translational and commercial spaces, to fabricate such diagnostic platforms. Engineered from organic or inorganic molecules, bioinspired systems are naturally equipped with biorecognition and stimuli-sensitive properties. Mechanisms of action of bioinspired materials are deeply connected with thermodynamically or kinetically controlled self-assembly at the molecular and supramolecular levels. Thus, integration of bioinspired materials into wearable devices, either as triggers or sensors, brings about unique device properties usable for detection, capture, or rapid readout for an analyte of interest. In this review, we present the basic principles and mechanisms of action of diagnostic devices engineered from bioinspired materials, describe current advances, and discuss future trends of the field, particularly in the context of cancer.

Improved outcomes for borderline resectable adenocarcinoma of the pancreas after neoadjuvant chemotherapy in a community cancer center.

BACKGROUND: Borderline resectable adenocarcinoma of the pancreas involves the major vascular structures adjacent to the pancreas and has traditionally led to poor resection rates and survival. Newer chemotherapy regimens have demonstrated improved response and resection rates. We performed a retrospective review of borderline resectable pancreatic cancers who presented to a community cancer program to determine the effect of neoadjuvant chemotherapy to improve resection rates and overall survival. METHODS: Records of all patients diagnosed with adenocarcinoma of the pancreas from January 1, 2015 to December 31, 2019 were reviewed to determine stage at presentation, resectablility status, treatment methods, surgical resection and survival. Borderline resectable status was determined by preoperative imaging in agreement with published criteria from the National Comprehensive Cancer Network (NCCN) Guidelines 2.2021. Data was collected and analyzed by standard t-test. This study was approved by the institution's IRB. RESULTS: During this time period 322 patients were diagnosed with ductal adenocarcinoma of the pancreas of which 151 (47%) were unresectable, 31 (10%) were locally advanced, 70 (22%) were borderline resectable, and 69 (21%) were resectable at the time of presentation. 36 (51%) of the borderline resectable patients underwent neoadjuvant chemotherapy at our institution with either FOLFIRINOX or gemcitibine/nab-Paclitaxel regimens and served as the basis for this analysis. After neoadjuvant chemotherapy 24 (68%) of the borderline-resectable patients were deemed suitable for surgical exploration. At exploration, 15 (64%) were resected with 9 (60%) achieving margin-free resection on final pathology. The overall survival of those that underwent resection was increased by 19.6 months compared to those that did not undergo surgery (35.4 versus 15.8 mos, p < 0.01). Overall morbidity after resection was 46% (33% class 1 or 2, 13% class 3) with 0% mortality at 90 days. CONCLUSIONS: Use of neoadjuvant chemotherapy for borderline resectable adenocarcinoma of the pancreas results in improved resection rates and overall survival in resected patients. This management strategy for ductal adenocarcinoma of the pancreas is safe and feasible in a community-based cancer program.

Cellulose nanofibers as Scaffold-forming materials for thin film drug delivery systems.

We explored the potential of cellulose nanofiber (CNF) for designing prolonged-release, thin-film drug delivery systems (TF-DDS). These delivery systems can be used as locally deployable drug-releasing scaffolds for achieving spatial and temporal control over therapeutic concentration in target tissues. Using doxorubicin (DOX) as a model anticancer drug, CNF-based TF-DDS were prepared using different film-formation processes, such as solvent casting and lyophilization. Formulations were prepared with or without the incorporation of additional macromolecular additives, such as gelatin, to include further biomechanical functionality. We studied the films for their mechanical properties, thermal stability, wettability, porosity and in vitro drug release properties. Our experimental results showed that CNF-based films, when prepared via solvent casting method, showed optimized performance in terms of DOX loading, and prolonged-release than those prepared via lyophilization-based fabrication processes. Scanning electron microscopy (SEM) analysis of the CNF-based films showed uniform distribution of fiber entanglement, which provided the scaffolds with sufficient porosity and tortuosity contributing to the sustained release of the drug from the delivery system. We also observed that surface layering of gelatin on CNF films via dip-coating significantly increased the mechanical strength and reduced the wettability of the films, and as such, affected drug release kinetics. The performance of the TF-DDS was evaluated in-vitro against two pancreatic cancer cell lines, i.e. MIA PaCa-2 and PANC-1. We observed that, along with the enhancement of mean dissolution time (MDT) of DOX, CNF-based TF-DDS were able to suppress the proliferation of pancreatic cancer cells in a time-dependent fashion, indicating that the drug liberated from the films were therapeutically active against cancer cells. Additionally, TF-DDS were also tested ex-vivo on patient-derived xenograft (PDX) model of pancreatic ductal adenocarcinoma (PDAC). We observed that DOX released from the TF-DDS was able to reduce Ki-67 positive, pancreatic cancer cells in these models.

Impact of Endocrinologist and Surgeon Density on Well-Differentiated Thyroid Cancer Survival.

BACKGROUND: The influence of provider density and access on well-differentiated thyroid cancer (DTC) survival is uncertain. METHODS: We used the SEER18 database to study DTC patients undergoing surgery from 2000-2012. County-level endocrinologist and surgeon density were calculated. We evaluated the relationship between provider density and cause-specific survival controlling for demographic, socioeconomic, and treatment characteristics. RESULTS: Median endocrinologist density was 1.4/100 000 residents, with 15.5% of patients living in a county with no endocrinologist. Survival increased by 11% for each endocrinologist/100,000 people (P = .007). Median surgeon density was 14.8/100 000 residents, with only 1.7% of patients living in a county with no general surgeon or otolaryngologist. No significant association between surgeon density and survival was identified (P = .06). Rural residence was independently associated with lower survival (P = .009). CONCLUSIONS: County-level endocrinologist density is associated with improved DTC survival. Results may reflect endocrinologist expertise, earlier diagnosis, or represent surrogacy for higher county-level access to specialized care.

How Should Surgical Palliative Success Be Defined?

Palliative surgery is often defined as surgical intervention with intent to improve a patient's quality of life by relieving suffering secondary to symptoms of advanced disease. In the context of shared decision making about palliative surgery intervention, tensions can arise between patient (or surrogate) and surgeon, who might not share goals and values. This article suggests that a surgeon's clinical and ethical duty is to identify goals of care, including those related to quality of life, from a patient's perspective and to consider how to achieve them.

Polymeric Composite Matrix with High Biobased Content as Pharmaceutically Relevant Molecular Encapsulation and Release Platform.

Drug delivery systems (DDS) that can temporally control the rate and extent of release of therapeutically active molecules find applications in many clinical settings, ranging from infection control to cancer therapy. With an aim to design a locally implantable, controlled-release DDS, we demonstrated the feasibility of using cellulose nanocrystal (CNC)-reinforced poly (l-lactic acid) (PLA) composite beads. The performance of the platform was evaluated using doxorubicin (DOX) as a model drug for applications in triple-negative breast cancer. A facile, nonsolvent-induced phase separation (NIPS) method was adopted to form composite beads. We observed that CNC loading within these beads played a critical role in the mechanical stability, porosity, water uptake, diffusion, release, and pharmacological activity of the drug from the delivery system. When loaded with DOX, composite beads significantly controlled the release of the drug in a pH-dependent pattern. For example, PLA/CNC beads containing 37.5 wt % of CNCs showed a biphasic release of DOX, where 41 and 82% of the loaded drug were released at pH 7.4 and pH 5.5, respectively, over 7 days. Drug release followed Korsmeyer's kinetics, indicating that the release mechanism was mostly diffusion and swelling-controlled. We showed that DOX released from drug-loaded PLA/CNC composite beads locally suppressed the growth and proliferation of triple-negative breast cancer cells, MBA-MB-231, via the apoptotic pathway. The efficacy of the DDS was evaluated in human tissue explants. We envision that such systems will find applications for designing biobased platforms with programmed stability and drug delivery functions.

Top Ten Tips Palliative Care Clinicians Should Know About Prognostication in Critical Illness and Heart, Kidney, and Liver Diseases.

Specialty palliative care (PC) clinicians are frequently asked to discuss prognosis with patients and their families. When conveying information about prognosis, PC clinicians need also to discuss the likelihood of prolonged hospitalization, cognitive and functional disabilities, and death. As PC moves further and further upstream, it is crucial that PC providers have a broad understanding of curative and palliative treatments for serious diseases and can collaborate in prognostication with specialists. In this article, we present 10 tips for PC clinicians to consider when caring and discussing prognosis for the seriously ill patients along with their caregivers and care teams. This is the second in a three-part series around prognostication in adult and pediatric PC.

Rural-urban and racial/ethnic trends and disparities in early-onset and average-onset colorectal cancer.

BACKGROUND: Incidence rates (IRs) of early-onset colorectal cancer (EOCRC) are increasing, whereas average-onset colorectal cancer (AOCRC) rates are decreasing. However, rural-urban and racial/ethnic differences in trends by age have not been explored. The objective of this study was to examine joint rural-urban and racial/ethnic trends and disparities in EOCRC and AOCRC IRs. METHODS: Surveillance, Epidemiology, and End Results data on the incidence of EOCRC (age, 20-49 years) and AOCRC (age, ≥50 years) were analyzed. Annual percent changes (APCs) in trends between 2000 and 2016 were calculated jointly by rurality and race/ethnicity. IRs and rate ratios were calculated for 2012-2016 by rurality, race/ethnicity, sex, and subsite. RESULTS: EOCRC IRs increased 35% from 10.44 to 14.09 per 100,000 in rural populations (APC, 2.09; P < .05) and nearly 20% from 9.37 to 11.20 per 100,000 in urban populations (APC, 1.26; P < .05). AOCRC rates decreased among both rural and urban populations, but the magnitude of improvement was greater in urban populations. EOCRC increased among non-Hispanic White (NHW) populations, although rural non-Hispanic Black (NHB) trends were stable. Between 2012 and 2016, EOCRC IRs were higher among all rural populations in comparison with urban populations, including NHW, NHB, and American Indian/Alaska Native populations. By sex, rural NHB women had the highest EOCRC IRs across subgroup comparisons, and this was driven primarily by colon cancer IRs 62% higher than those of their urban peers. CONCLUSIONS: EOCRC IRs increased in rural and urban populations, but the increase was greater in rural populations. NHB and American Indian/Alaska Native populations had particularly notable rural-urban disparities. Future research should examine the etiology of these trends.

Impact of Rurality on National Trends in Thyroid Cancer Incidence and Long-Term Survival.

PURPOSE: Thyroid cancer incidence is rising, possibly secondary to increased imaging and surveillance. Based on rural access to care disparities, we hypothesized that incidence would be greater in urban compared to rural counties with no significant difference in long-term survival. METHODS: An observational study was performed on thyroid cancer patients using Surveillance Epidemiology and End Results data (2000-2012). Age-adjusted incidence rates, incidence rate ratios, and survival rates were calculated across rural-urban designations. FINDINGS: Incidence rates were 11.2, 9.8, and 10.1 per 100,000 for urban, rural-adjacent, and rural-nonadjacent counties, respectively. Statistically significantly lower incidence was noted in rural-adjacent and rural-nonadjacent compared to urban areas. Five-year and 10-year survival was significantly lower in rural-nonadjacent counties compared to urban counties. CONCLUSIONS: Higher incidence and increased long-term survival for thyroid cancer were noted in urban areas compared to rural areas. It is uncertain if rural-urban differences in long-term survival reflect health care disparities, differences in therapy, or other origins.

Determinants of 90-day readmission following ventral hernia repair with and without myocutaneous flap reconstruction: a National Readmissions Database analysis.

BACKGROUND: Readmission status is an important clinical component of healthcare outcomes. 90-day readmission following complex open ventral hernia repair has not been well studied with national level data. This study aims to compare readmission rates for patients undergoing standard vs. complex (myocutaneous flap-based) ventral hernia repair. We hypothesize that complexity of reconstruction will be an independent predictor of readmission after ventral hernia repair. METHODS: A retrospective cohort study was performed with 1:1 matching of hernia repair type using the National Readmissions Database. Patients were selected using ICD-9 codes corresponding to ventral hernia repair with or without myocutaneous flap. 90-day readmissions were determined on patients within the first through third quarters of each year. After matching, a multivariable logistic regression analysis was performed using confounding variables including hospital setting, comorbidities, type of repair, urgency of repair, sociodemographic status, and payer. Likelihood of 90-day readmission was calculated from odds ratios. RESULTS: Readmission rates were 19.1% (38,313 out of 200,266) and 22.5% (692 out of 3075) at 90-day for standard ventral hernia repair and complex ventral hernia repair, respectively. 3116 standard ventral hernia repair patients were matched with 3074 complex ventral hernia repair patients. After matching there was a significantly increased readmission rate for repairs involving myocutaneous flaps, with odds ratio (OR) 1.30 (95% CI 1.22-1.60). Payer status (OR 1.82; 95% CI 1.21-2.74), teaching hospital status (OR 1.42; 95% CI 1.23-1.64) and income quartile (OR 1.35; CI 1.10-1.65) were independent predictors of readmission. CONCLUSIONS: Patients undergoing myocutaneous flap-based reconstruction have higher readmission rates than those undergoing less complex ventral hernia repair. Socioeconomic disparity as reflected in payer status is a particularly strong predictor of readmission. The data support the concept that focused efforts are needed to optimize patient outcomes for patients requiring more complex repair, including socioeconomically disadvantaged patient populations.

National Trends in General Surgery Resident Exposure to Complex Oncology-Relevant Cases.

OBJECTIVE: To evaluate trends in surgical resident exposure to complex oncologic procedures in order to determine whether additional fellowship training is necessary. DESIGN: An observational study of national Accreditation Council for Graduate Medical Education case log statistical reports was conducted to determine the average number of cases for selected oncology-relevant procedures completed during training. Linear regression and Cusick trend tests were used to assess temporal trends with the null hypothesis assuming an estimated slope of zero. Instrumental variable estimation was used to study the effect of duty-hour restrictions on oncologic cases per year. SETTING: United States general surgery residency training programs. PARTICIPANTS: Graduating surgical residents completing their training between 2000 and 2016. RESULTS: Across the study interval, mean case volume was 950.6 ± 29.7 (standard deviation) cases with 38.9 ± 3.1 complex oncologic cases per graduating resident. Decreasing trends were noted for average exposure to lymphadenectomies (-7.8 cases/decade; 95% confidence interval [CI] -8.8 to -6.8) and low rectal procedures (-0.9 cases/decade; 95% CI -1.2 to -0.6). There was no clinically important change in complex soft-tissue resections and foregut cases. A significant increase was seen in number of hepatopancreaticobiliary procedures (+3.9 cases/decade; 95% CI 3.1-4.7). Using instrumental variable estimation, there was a modest decline in cancer-relevant cases by 5.0 cases/decade (95% CI 4.5-5.6), while there was an increase in 38.5 total cases/decade (95% CI 10.4-66.7) associated with duty-hour restrictions. CONCLUSIONS: Case numbers for several complex oncologic procedures remain low, justifying a need for further fellowship training depending on individual resident experience.

Survival Implications of Increased Utilization of Local Excision for cT1N0 Esophageal Cancer.

OBJECTIVE: We hypothesized that patients with cT1N0 esophageal cancer undergoing local excision would have lower survival compared with esophagectomy due to potential discordant staging. BACKGROUND: Local excision has become an attractive alternative for management of early esophageal cancer, avoiding the morbidity of esophagectomy. It is uncertain if occult nodal metastasis impacts survival. METHODS: An observational study was conducted using the National Cancer Database (1998-2012) for patients with clinical T1N0 esophageal cancer who underwent local excision (n = 1625) or esophagectomy (n = 3255). RESULTS: The proportion of patients undergoing local excision increased from 12% in 1998 to 50% in 2012 (P < 0.001). After esophagectomy, 61% of cT1N0 cancers had concordant clinical and pathological staging, with 5.2% having positive nodal disease; 37% were staged concordant after local excision, with excess missing data (60%). Ninety-day mortality was 7.4% after esophagectomy compared with 2.8% after local excision (P < 0.001). While no significant difference was seen in unadjusted survival, adjusted Cox regression analysis indicated worse survival after esophagectomy compared with local excision for all cases [hazard ratio (HR) 1.57, 95% confidence interval (CI) 1.27-1.95] and for patients with concordant staging (HR 1.68, 95% CI 1.23-2.28). CONCLUSIONS: Local excision for cT1N0 esophageal cancer has increased over time. Contrary to our hypothesis, despite incomplete nodal staging, patients undergoing local excision have favorable survival, particularly in the adenocarcinoma subgroup. This may reflect early differences in mortality due to differences in procedure-related complications and/or selection bias. As this study has limited power to compare outcomes between T1a and T1b cancers, further analysis is warranted.

Author Correction: Integrated molecular subtyping defines a curable oligometastatic state in colorectal liver metastasis.

In the originally published version of this Article, the affiliation details for Kevin P. White inadvertently omitted 'Tempus Labs, Chicago, IL, 60654, USA'. This has now been corrected in both the PDF and HTML versions of the Article.

Integrated molecular subtyping defines a curable oligometastatic state in colorectal liver metastasis.

The oligometastasis hypothesis suggests a spectrum of metastatic virulence where some metastases are limited in extent and curable with focal therapies. A subset of patients with metastatic colorectal cancer achieves prolonged survival after resection of liver metastases consistent with oligometastasis. Here we define three robust subtypes of de novo colorectal liver metastasis through integrative molecular analysis. Patients with metastases exhibiting MSI-independent immune activation experience the most favorable survival. Subtypes with adverse outcomes demonstrate VEGFA amplification in concert with (i) stromal, mesenchymal, and angiogenic signatures, or (ii) exclusive NOTCH1 and PIK3C2B mutations with E2F/MYC activation. Molecular subtypes complement clinical risk stratification to distinguish low-risk, intermediate-risk, and high-risk patients with 10-year overall survivals of 94%, 45%, and 19%, respectively. Our findings provide a framework for integrated classification and treatment of metastasis and support the biological basis of curable oligometastatic colorectal cancer. These concepts may be applicable to many patients with metastatic cancer.

Interdisciplinary Oncology Education: a National Survey of Trainees and Program Directors in the United States.

Oncologists must have a strong understanding of collaborating specialties in order to deliver optimal cancer care. The objective of this study was to quantify current interdisciplinary oncology education among oncology training programs across the USA, identify effective teaching modalities, and assess communication skills training. Web-based surveys were sent to oncology trainees and program directors (PDs) across the USA on April 1, 2013 and October 8, 2013, respectively. Question responses were Yes/No, five-point Likert scales (1 = not at all, 2 = somewhat, 3 = moderately, 4 = quite, 5 = extremely), or free response. Respondents included the following (trainees/PDs): 254/55 medical oncology, 160/42 surgical oncology, 102/24 radiation oncology, and 41/20 hospice and palliative medicine (HPM). Trainees consistently reported lower rates of interdisciplinary education for each specialty compared with PDs as follows: medical oncology 57 vs. 77% (p < 0.01), surgical oncology 30 vs. 44% (p < 0.01), radiation oncology 70 vs. 89% (p < 0.01), geriatric oncology 19 vs. 30% (p < 0.01), and HPM 55 vs. 74% (p < 0.01). The predominant teaching method used (lectures vs. rotations vs. tumor board attendance vs. workshop vs. other) varied according to which discipline was being taught. The usefulness of each teaching method was rated statistically different by trainees for learning about select disciplines. Furthermore, statistically significant differences were found between PDs and trainees for the perceived usefulness of several teaching modalities. This study highlights a deficiency of interdisciplinary education among oncology training programs in the USA. Efforts to increase interdisciplinary education opportunities during training may ultimately translate into improved collaboration and quality of cancer care.

Impact of rural-urban status on survival after mastectomy without reconstruction versus mastectomy with reconstruction.

BACKGROUND: Disparities in access to care exist for breast cancer patients, including access to surgeons performing reconstruction. We hypothesized rural patients have delayed time to surgery after mastectomy with reconstruction with implications on survival. METHODS: An observational study was conducted using the National Cancer Database on patients with breast cancer from 2003 to 2007 who underwent mastectomy, with or without reconstruction from 2003 to 2007 (n = 90,319). RESULTS: Patients with, and without, reconstruction varied by demographics, facility type and stage. Time to surgery was longer for mastectomy with reconstruction. Unadjusted analysis demonstrated marginally decreased survival for rural patients undergoing mastectomy alone but not for mastectomy with reconstruction. Cox proportional hazards analysis revealed no significant differences by rural-urban status, but a survival advantage was seen after mastectomy with reconstruction, which persisted up to a delay of 180 days. CONCLUSION: Patients who underwent reconstruction had improved survival. Time to surgery is shorter for rural patients (for all types of mastectomy). We found no significant rural-urban disparity in survival.