Minimally invasive management of large duodenal lipoma: endoscopic submucosal dissection

Objective This study was performed to compare the clinical outcomes of large duodenal lipomas (DLs) of ≥2 cm between endoscopic submucosal dissection (ESD) and endoscopic full-thickness resection (EFTR). Methods This retrospective study included patients who underwent endoscopic resection of large DLs from June 2017 to March 2021 at our hospital. Clinicopathologic features, clinical outcomes, and follow-up endoscopy findings were retrospectively reviewed. Results Twenty-three patients (12 men) with a mean age of 57.4 years were included. The median tumor size was 28.4 ± 13.3 mm. ESD was performed in 19 patients, and EFTR was performed in 4. Complete resection was achieved in 21 patients. The operative time and postoperative hospital stay were significantly shorter in the ESD than EFTR group. Four patients in the EFTR group developed a fever; no other adverse events occurred. No patients required surgical intervention. During the average follow-up of 21.1 months, no residual tumor, recurrence, or metastasis was observed. Conclusion Both ESD and EFTR provide minimally invasive, localized treatment of selected DLs. ESD might have some advantages in resecting large DLs in terms of procedure time and hospitalization.

Landscape of Immune-Related Markers and Potential Therapeutic Targets in Soft Tissue Sarcoma

Soft tissue sarcomas, depending on the subtype and grade, frequently recur and become metastatic after localized treatment. There is now great interest in applying immunotherapy to sarcomas to immuno-profile the different subtypes and immune monitor for prognosis. Our group previously showed that key immunotherapy target genes are present in sarcomas. Here, we extend our findings by demonstrating that sarcomas with a relatively high mutational load are likely to be more sensitive to immunotherapy compared to sarcomas with a lower mutation load. We also show that sarcomas with a higher mutation load are associated with the expression of key immune-related genes. We found that CD8+ T cells are present in sarcoma subtypes and that PD-L2 is highly expressed. These findings further define potential mechanisms behind the immunotherapy response of specific sarcoma subtypes and can be used to develop more optimal treatments in the future.

Hyaluronic Acid-Binding, Anionic, Nanoparticles Inhibit ECM Degradation and Restore Compressive Stiffness in Aggrecan-Depleted Articular Cartilage Explants

Joint trauma results in the production of inflammatory cytokines that stimulate the secretion of catabolic enzymes, which degrade articular cartilage. Molecular fragments of the degraded articular cartilage further stimulate inflammatory cytokine production, with this process eventually resulting in post-traumatic osteoarthritis (PTOA). The loss of matrix component aggrecan occurs early in the progression of PTOA and results in the loss of compressive stiffness in articular cartilage. Aggrecan is highly sulfated, associates with hyaluronic acid (HA), and supports the compressive stiffness in cartilage. Presented here, we conjugated the HA-binding peptide GAHWQFNALTVRGSG (GAH) to anionic nanoparticles (hNPs). Nanoparticles conjugated with roughly 19 GAH peptides, termed 19 GAH-hNP, bound to HA in solution and increased the dynamic viscosity by 94.1% compared to an HA solution treated with unconjugated hNPs. Moreover, treating aggrecan-depleted (AD) cartilage explants with 0.10 mg of 19 GAH-hNP restored the cartilage compressive stiffness to healthy levels six days after a single nanoparticle treatment. Treatment of AD cartilage with 0.10 mg of 19 GAH-hNP inhibited the degradation of articular cartilage. Treated AD cartilage had 409% more collagen type II and 598% more GAG content than untreated-AD explants. The 19 GAH-hNP therapeutic slowed ECM degradation in AD cartilage explants, restored the compressive stiffness of damaged cartilage, and showed promise as a localized treatment for PTOA.

IMPROVEMENT OF THE MICROFLUIDIC DEVICE FOR THE GENERATION OF MONODISPERSE MICROBUBBLES AS DRUG TRANSPORT SYSTEMS

INTRODUCTION: The localized delivery of drugs has been established since the early eighties of the 20th century as a promising alternative for the localized treatment of tumours, based on the mitigation of side effects produced by traditional methods, notably the administration of chemotherapy by systemic route. Countless scientific works have been dealing with this theme in an attempt to make this therapeutic technique viable and accessible. One of the ways to take the drug to the chosen site is through the use of microbubbles as drug carrier units activated through an ultrasonic field with adequate wavelength and frequency. Therefore, these units must have very peculiar characteristics, such as dimensions, homogeneity, echogenicity and structural characteristics, in addition to the ability to take the therapeutic vector intact to the desired location. In the generation of microbubbles, microfluidic devices of different geometries and different configurations are used, according to the state of the art related to this theme. DEVELOPMENT: In this work the technique used is the fabrication of micro fluidic devices using 3D printing. With this technique, it is possible to manufacture the devices in a single step, eliminating time-consuming and more complex intermediate procedures. The devices were manufactured using an Object Eden 250 printer, using the transparent resin VeroClear®. With these devices it was possible to produce microbubbles with diameters of the order of 16-73 µm with degrees of poly dispersion less than 1%. However, there are difficulties to be overcome, notably with regard to the final composition of the devices. Due to the physical characteristics of the microbubble, notably in relation to its lipid coating layer, the search for drug transport systems is an important strategy. CONCLUSION: In this work, an account of these difficulties will be made, in addition to the proposition of alternatives to overcome them. Additionally, compatible drugs will be suggested to be attached to microbubbles according to their structural composition.

A Conceptual Study of Upanaha Swedana

Swedana Karma is undertaken by inducing sweating from the application of heat. There are many methods used to achieve this, with Upanaha Swedana being one of them. Upanaha Swedana is a standard treatment modality used in Ayurveda for the management of pain and inflammation. It is a localized treatment wherein a combination of medicinal drugs are prepared, made into a poultice, heated and applied at the affected site. This is meant to reduce the local inflammation and act as a topical analgesic. The procedure is divided into three phases which are: Purva Karma (pre-therapy procedures), the preparation of the Upanaha Swedana material is done, Pradhana Karma (main therapeutic procedures) the prepared Upanaha Swedana material is applied to the patient and Paschat Karma (post-therapy procedures) after waiting the specified times, the Upahana Swedana is removed following proper procedures. The present conceptual study was done based on the need of the day to elaborate the process of conducting Upanaha Swedana. For this, various Ayurvedic texts, digital libraries referencing Samhita were searched and the following headings were selected, types of data, types of reports and functionalities. This article seeks to explore this treatment modality and outline the general approach to be followed while conducting the procedure of Upanaha Swedana.

Anticancer Potential Of Cephalotaxine and Derivatives as an Alternative for Invasive Therapies

Cancer is identified by the abnormal accumulation of rapidly dividing cells, serving as the collective term for a multitude of similar conditions categorized through cell growth and proliferation. The disease continues to lead death tolls worldwide and extends to communities across the board in terms of socioeconomic status.(^1) From 1991 to 2017, experts recorded a slight drop in cancer death rates, which can be accredited to an influx of scientific advancements within the past decade that allowed for the implementation of targeted therapy.(^1) In preclinical research, this therapy implies the conjugation of independent drugs retaining anti-carcinogenic properties. The current state of cancer pathology is observed to be non-specific and is, oftentimes, taxing on the patient, proving the need for localized treatment and more efficient drugs. This article analyzes the effectiveness of one compound under the harringtonine alkaloid family, cephalotaxine (CET).(^27) In this work, our team examines the biochemical profile of CET and congener homoharringtonine to hypothesize cephalotaxine’s efficacy as an alternative to invasive cancer therapy.

Comorbidities at time of diagnosis as a predictor of more or less aggressive treatment modalities in early-invasive breast cancer.

e12591 Background: Comorbidities and advanced age have been shown to play important roles in breast cancer treatment and outcomes. Reduced doses of chemotherapy, worse treatment-related side-effects, poor performance status in patients with significant comorbidities, and the biological interplay between other diseases and cancer may also play roles. We evaluated the relationship between age and pre-existing comorbidities and receipt of local and systemic therapy in a cohort of African American (AA) women with early invasive breast cancer. Methods: The study population included 1,169 AJCC stage I-III invasive breast cancer survivors from the Detroit Research on Cancer Survivors (ROCS) study, a large cohort of AA cancer survivors. Comorbidities (both individual diseases and a combined count that was categorized as low/medium/high comorbidity burden), age at diagnosis, and other demographic variables were obtained from self-reported standardized questionnaires. Cancer-related variables including treatment were obtained from the Metropolitan Detroit Cancer Surveillance System registry. Recommended treatment was subdivided into localized (surgery ± radiation; N = 1,156), hormonal (N = 848) and chemotherapy (N = 680). Logistic regression estimated the associations between age and pre-existing comorbid conditions and the receipt of recommended treatments. Adjusted models included variables that were selected a priori and were significant predictors in univariate analysis. Results: Most women received recommended localized treatment (82.6%), hormone treatment (73.7%), and chemotherapy (79.9%). There were no differences in receipt of localized treatment based on age or comorbidity burden in adjusted analyses. However, arthritis and depression were significantly associated with not receiving recommended localized treatment (Odds ratio (OR): 0.66, 95% CI: 0.47, 0.93 and OR: 0.53, 95% CI: 0.36, 0.78, respectively). Women with a history of obesity (BMI ≥30) were more likely to receive recommended hormone therapy (OR: 1.64, 95% CI: 1.19, 2.26), while women with congestive heart failure were less likely (OR: 0.46, 95% CI: 0.23, 0.90). Receipt of recommended chemotherapy was less likely for those with increasing age (Ptrend< 0.01) and increasing comorbidity burden (Ptrend= 0.02). Those with a history of arthritis (OR: 0.66, 95% CI: 0.44, 0.99) and hypercholesterolemia (OR: 0.62, 95% CI: 0.41, 0.95) were also less likely to receive recommended chemotherapy. Conclusions: Advanced age and presence of pre-existing co-morbid medical conditions appears to influence the receipt of chemotherapy, while individual conditions were associated with receipt of local treatment or hormone therapy in a cohort of AA survivors, suggesting the importance of providing comprehensive medical care for all women with early invasive breast cancer.

Impact of lenvatinib (LEN) dose-intensity and starting dose on survival among patients with advanced hepatocellular carcinoma (HCC): Results from a Canadian multicenter database (HCC CHORD).

e16142 Background: The REFLECT trial established LEN as a first-line treatment option for HCC. However, decreased LEN exposure is common due to adverse events leading to dose reductions and treatment discontinuations. The aim of this study was to evaluate whether starting dose or dose-intensity of LEN affects survival. To our knowledge, this is the first study to examine dosing of LEN and survival in HCC patients treated outside of Asia. Methods: From July 2018 to December 2019, HCC patients treated with first-line LEN from 10 different Canadian cancer centers were included. Overall survival (OS), progression-free survival (PFS), disease control rate (DCR) and objective response rate (ORR) were retrospectively analyzed and compared across different mean dose-intensities (> 66.7% vs <=66.7%) and starting dose groups (Full vs reduced). Survival outcomes were assessed with Kaplan-Meier curves and Cox proportional hazards models. DCR and ORR were determined radiographically according to the treating physician´s assessment in clinical notes and not RECIST 1.1 or mRECIST. Results: A total of 173 patients were included. Median age was 67 years, 77% were men and 23% East Asian. The most frequent causes of liver disease were hepatitis C (38%) and B (20%). 56% of patients received localized treatment prior to LEN. Of those, 24% had TACE, 6% TARE and 8% had liver transplant. Before starting LEN 31% of patients were ECOG 0 and 57% were ECOG 1. Most patients were Child-Pugh A (81%) and BCLC stage C (73%). Main portal vein invasion was present in 15% of the patients. Median follow-up was 4.5 months. LEN was started at full dose in 54% of patients and 60% had a mean dose intensity greater than 66.7%. ORR, PFS and OS results and their comparison between the different starting dose and dose-intensities are shown in the table. In a multivariate model that adjusted for age, gender, stage, ECOG, Child-Pugh, BCLC, cirrhosis, liver etiology disease (hepatitis B, C and non-viral), presence of tumor thrombus, prior transplant and localized treatment, dose intensity (>66.7 vs <=66.7% [HR 0.70, 95% CI 0.42-1.18; p=0.18]) was not a predictor of survival. Conclusions: In HCC patients starting LEN at a reduced dose does not appear to compromise survival. LEN dose-intensity of > 66.7% was associated with improved survival, but not after controlling for potential confounders.[Table: see text]