Improved Quality of 3D-Printed Tissue Constructs Through Enhanced Mixing of Alginate Hydrogels

While alginate hydrogel is a desirable material platform for Solid Freeform Fabrication (SFF) of cell-seeded tissue engineering scaffolds, achieving consistently high-quality results can be challenging. Local variations in the material properties cause inconsistent material deposition behavior and consequently decrease the resultant geometric fidelity of the construct. The effects of gel mixing on material property consistency, geometric fidelity, and cell viability were characterized in an attempt to improve the formulation’s compatibility with SFF processing. Material homogeneity was quantified through a novel experimental setup composed of an EnduraTEC mechanical test-frame and custom syringe-extrusion jig. Cell viability and geometric fidelity were assessed using standard protocol. The baseline mechanical stiffness of the printed samples was 16±3 kPa (n=6). We found that increasing mixing reduced material inconsistency and improved geometric fidelity, without adversely affecting cell viability: the printed construct quality was drastically improved by increasing mixing well beyond previously established limits.Mechanical Engineerin

Associations of CDH1 germline variant location and cancer phenotype in families with hereditary diffuse gastric cancer (HDGC)

INTRODUCTION: Hereditary diffuse gastric cancer (HDGC) is a cancer syndrome associated with variants in E-cadherin (CDH1), diffuse gastric cancer and lobular breast cancer. There is considerable heterogeneity in its clinical manifestations. This study aimed to determine associations between CDH1 germline variant status and clinical phenotypes of HDGC. METHODS: One hundred and fifty-two HDGC families, including six previously unreported families, were identified. CDH1 gene-specific guidelines released by the Clinical Genome Resource (ClinGen) CDH1 Variant Curation Expert Panel were applied for pathogenicity classification of truncating, missense and splice site CDH1 germline variants. We evaluated ORs between location of truncating variants of CDH1 and incidence of colorectal cancer, breast cancer and cancer at young age (gastric cancer at \u3c40 or breast cancer \u3c50 years of age). RESULTS: Frequency of truncating germline CDH1 variants varied across functional domains of the E-cadherin receptor gene and was highest in linker (0.05785 counts/base pair; p=0.0111) and PRE regions (0.10000; p=0.0059). Families with truncating CDH1 germline variants located in the PRE-PRO region were six times more likely to have family members affected by colorectal cancer (OR 6.20, 95% CI 1.79 to 21.48; p=0.004) compared with germline variants in other regions. Variants in the intracellular E-cadherin region were protective for cancer at young age (OR 0.2, 95% CI 0.06 to 0.64; p=0.0071) and in the linker regions for breast cancer (OR 0.35, 95% CI 0.12 to 0.99; p=0.0493). Different CDH1 genotypes were associated with different intracellular signalling activation levels including different p-ERK, p-mTOR and β-catenin levels in early submucosal T1a lesions of HDGC families with different CDH1 variants. CONCLUSION: Type and location of CDH1 germline variants may help to identify families at increased risk for concomitant cancers that might benefit from individualised surveillance and intervention strategies

Recent Advances in Minimally Invasive Liver Resection for Colorectal Cancer Liver Metastases—A Review

Minimally invasive surgical (MIS) approaches to liver resection have been increasingly adopted into use for surgery on colorectal cancer liver metastases. The purpose of this review is to evaluate the outcomes when comparing laparoscopic liver resection (LLR), robotic liver resection (RLR), and open liver resection (OLR) for colorectal cancer liver metastases (CRLM) in 39 studies (2009–2022) that include a case-matched series, propensity score analyses, and three randomized clinical trials. LLR is associated with less intraoperative blood loss and shorter hospital stay compared with OLR. LLR can be performed with comparable operative time. LLR has similar rates of perioperative complications and mortality as OLR. There were no significant differences in 5-year overall or disease-free survival between approaches. Robotic liver resection (RLR) has comparable perioperative safety to LLR and may improve rates of R0 resection in certain patients. Finally, MIS approaches to the hepatic resection of CRLM reduce the time from liver resection to initiation of adjuvant chemotherapy. Thus, MIS liver surgery should be considered in the array of options for patients with CRLM, though thoughtful patient selection and surgeon experience should be part of that decision

Recent Advances in Minimally Invasive Liver Resection for Colorectal Cancer Liver Metastases—A Review

Minimally invasive surgical (MIS) approaches to liver resection have been increasingly adopted into use for surgery on colorectal cancer liver metastases. The purpose of this review is to evaluate the outcomes when comparing laparoscopic liver resection (LLR), robotic liver resection (RLR), and open liver resection (OLR) for colorectal cancer liver metastases (CRLM) in 39 studies (2009–2022) that include a case-matched series, propensity score analyses, and three randomized clinical trials. LLR is associated with less intraoperative blood loss and shorter hospital stay compared with OLR. LLR can be performed with comparable operative time. LLR has similar rates of perioperative complications and mortality as OLR. There were no significant differences in 5-year overall or disease-free survival between approaches. Robotic liver resection (RLR) has comparable perioperative safety to LLR and may improve rates of R0 resection in certain patients. Finally, MIS approaches to the hepatic resection of CRLM reduce the time from liver resection to initiation of adjuvant chemotherapy. Thus, MIS liver surgery should be considered in the array of options for patients with CRLM, though thoughtful patient selection and surgeon experience should be part of that decision

Outcomes and Patient Selection in Laparoscopic vs. Open Liver Resection for HCC and Colorectal Cancer Liver Metastasis

Hepatocellular carcinoma (HCC) and colorectal liver metastasis (CRLM) are the two most common malignant tumors that require liver resection. While liver transplantation is the best treatment for HCC, organ shortages and high costs limit the availability of this option for many patients and make resection the mainstay of treatment. For patients with CRLM, surgical resection with negative margins is the only potentially curative option. Over the last two decades, laparoscopic liver resection (LLR) has been increasingly adopted for the resection of a variety of tumors and was found to have similar long-term outcomes compared to open liver resection (OLR) while offering the benefits of improved short-term outcomes. In this review, we discuss the current literature on the outcomes of LLR vs. OLR for patients with HCC and CRLM. Although the use of LLR for HCC and CRLM is increasing, it is not appropriate for all patients. We describe an approach to selecting patients best-suited for LLR. The four common difficulty-scoring systems for LLR are summarized. Additionally, we review the current evidence behind the emerging robotically assisted liver resection technology