Chemotherapy switch for nonresponse or progression on neoadjuvant chemotherapy for pancreatic adenocarcinoma.

Background And Objectives: Patients with localized pancreatic adenocarcinoma who do not respond to neoadjuvant therapy present a challenge. We sought to define the characteristics and outcomes of those patients to guide clinical practice.

Methods: Patients included were those without evidence of biochemical or radiographic response and no evidence of distant progression at the first reassessment after initiation of therapy.

High Risk, High Reward: Frailty in Colorectal Cancer Surgery is Associated with Worse Postoperative Outcomes but Equivalent Long-Term Oncologic Outcomes.

Background: Frailty is a physiologic state that affects perioperative outcomes. Studies evaluating the impact of frailty on long-term oncologic outcomes are limited. This study evaluated perioperative and long-term oncologic outcomes for elderly patients undergoing colorectal surgery.

An immune-inflamed tumor microenvironment as defined by CD8 score is associated with favorable oncologic outcomes in hepatocellular carcinoma independent of measures of tumor mutational burden.

Despite low mutational burden, immune checkpoint inhibitors have demonstrated promising results in a significant minority of hepatocellular carcinoma (HCC) patients with advanced disease. We hypothesized that HCC patients with higher levels of CD8+ T cell infiltration reflect an immune-inflamed cohort which has improved oncologic outcomes. 355 HCC patients with clinical and transcriptome data in the Cancer Genome Atlas (TCGA) and 151 HCC patients from cohort GSE7624 were analyzed.

Regional CAR T cell therapy: An ignition key for systemic immunity in solid tumors.

The success of chimeric antigen receptor (CAR) T cell therapy in solid tumors, unlike in hematologic malignancies, is limited by inadequate tumor infiltration and T cell dysfunction and exhaustion. Regional delivery of CAR T cells in patients with solid tumors is safe and feasible; promotes infiltration, proliferation, and trafficking; and ignites functionally persisting systemic immunity.

A case from the future of HPB surgical oncology: resection of biliary tract cancer after immunotherapy.

Biliary tract cancers (BTCs) have limited response to systemic therapy and poor prognosis. Immunotherapy in BTCs has been investigated in recent years. Here, we report a case of locally advanced, unresectable gallbladder adenocarcinoma that progressed on chemotherapy.

Enhanced DNA Repair Pathway is Associated with Cell Proliferation and Worse Survival in Hepatocellular Carcinoma (HCC).

Hepatocellular carcinoma (HCC) is one of the most common malignancies and a leading cause of cancer-related deaths worldwide. In this study, a total of 749 HCC patients from 5 cohorts were studied to examine the relationships between enhancement of DNA repair and cancer aggressiveness, tumor immune microenvironment, and patient survival in HCC, utilizing a DNA repair pathway score. Our findings suggest that the DNA repair pathway was not only enhanced by the stepwise carcinogenic process of HCC, but also significantly enhanced in grade 3 HCC compared with grade 1 and 2 tumors.

Re: AB (Termination of Pregnancy) [2019] EWCA CIV 1215: 'Wishes and Feelings' Under the Mental Capacity Act 2005.

In Re: AB (Termination of Pregnancy), the Court of Appeal was asked to consider an assumption made about the future living arrangements of a pregnant patient, and the weight to be ascribed to her wishes and feelings when she had no real understanding of her predicament. This commentary explores the importance of taking into account the perspective of the patient, even if suffering from a mental disorder, and it will analyse the existing common law to show that the weaker the ability of the patient to form her own wishes and feelings, the more appropriate it would be to rely on the remaining evidence.

Combination Immunotherapy with CAR T Cells and Checkpoint Blockade for the Treatment of Solid Tumors.

Checkpoint blockade (CPB) therapy can elicit durable clinical responses by reactivating an exhausted immune response. However, response rates remain limited, likely secondary to a lack of a tumor-reactive immune infiltrate. Chimeric antigen receptor (CAR) T cells may provide the necessary tumor-targeting immune infiltrate and a highly specific antitumor immune response.

Gallbladder Cancer: Managing the Incidental Diagnosis.

Managing patients with incidental gallbladder cancer requires stratifying patients risk for recurrence and an appreciation for the recurrence patterns characterizing this malignancy. Although standard management includes reresection to remove sites at risk of harboring residual disease and to achieve negative resection margin status, the decision to perform surgery is tempered by an early and frequent distant recurrence, the most common cause of surgical failure. High-risk patients may benefit from neoadjuvant chemotherapy before reresection.

Selecting treatment sequence for patients with incidental gallbladder cancer: a neoadjuvant approach versus upfront surgery.

At MSKCC, over 50% of the patients presenting with gallbladder cancer have been diagnosed incidentally following elective cholecystectomy for presumed benign disease. While traditional management of incidental gallbladder cancer (IGBC) dictates re-resection with the ultimate goal of achieving cure, surgical decision-making must take into account that this malignancy is characterized by poor tumor biology with frequent distant recurrence. Since early and frequent distant recurrence is the most common cause of surgical failure, the surgical oncologist's goal should be to selectively re-resect only those patients most likely to benefit from an operation.

A Gift or a Waste? Quintavalle, Surplus Embryos and the Abortion Act 1967.

The destruction of an embryo must be justified in law. This is to prevent frivolous wastage and to show the respect afforded by the Warnock Report (1984). For example, embryonic destruction during pregnancy is underpinned by the Abortion Act 1967, and embryonic destruction during fertility treatment is regulated by the Human Fertilisation and Embryology Act 1990.

Human CAR T cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated inhibition.

Following immune attack, solid tumors upregulate coinhibitory ligands that bind to inhibitory receptors on T cells. This adaptive resistance compromises the efficacy of chimeric antigen receptor (CAR) T cell therapies, which redirect T cells to solid tumors. Here, we investigated whether programmed death-1-mediated (PD-1-mediated) T cell exhaustion affects mesothelin-targeted CAR T cells and explored cell-intrinsic strategies to overcome inhibition of CAR T cells.

The Interfamilial Principle and the Harvest Festival.

It is widely accepted that younger children can act as saviour siblings by donating cord blood or bone marrow to their gravely-ill brothers or sisters. However, it is under dispute whether these procedures are in the best interests of the child. This article suggests that parents may be relying on a thinly-veiled interfamilial approach, where the wider benefit to the whole family is used to justify the procedure to the Human Tissue Authority in the United Kingdom.

Quintavalle: The Quandary in Bioethics.

The case of presents a handful of legal problems. The biggest legal query to arise from the case is the inevitable harvest of babies, toddlers and very young children for their bone marrow. This article unpacks the judicial story behind to reveal how the strict provisions of the Human Fertilisation and Embryology Act 1990--namely 'suitable condition' under schedule 2 paragraph 1(1)(a) and 'treatment services' and 'assisting' under section 2(1)--were widely misinterpreted to introduce the social selection of embryos into law.

Gillick, bone marrow and teenagers.

The Human Tissue Authority can authorise a bone marrow harvest on a child of any age if a person with parental responsibility consents to the procedure. Older children have the legal capacity to consent to medical procedures under Gillick, but it is unclear if Gillick can be applied to non-therapeutic medical procedures. The relevant donation guidelines state that the High Court shall be consulted in the event of a disagreement, but what is in the best interests of the teenage donor under s.

Tumor Budding Correlates With the Protumor Immune Microenvironment and Is an Independent Prognostic Factor for Recurrence of Stage I Lung Adenocarcinoma.

Background: Immune cell infiltration associated with tumor capsule disruption and tumor budding has been shown to reflect invasiveness, metastasis, and unfavorable prognosis in colorectal cancer. We investigated the influence of tumor budding on prognosis and its association with the immune microenvironment in lung adenocarcinoma.

Methods: Tumor slides from resected stage I lung adenocarcinomas were reviewed (n = 524 and n = 514, for training and validation cohorts, respectively) for assessment of tumor budding.

Regional delivery of mesothelin-targeted CAR T cell therapy generates potent and long-lasting CD4-dependent tumor immunity.

Translating the recent success of chimeric antigen receptor (CAR) T cell therapy for hematological malignancies to solid tumors will necessitate overcoming several obstacles, including inefficient T cell tumor infiltration and insufficient functional persistence. Taking advantage of an orthotopic model that faithfully mimics human pleural malignancy, we evaluated two routes of administration of mesothelin-targeted T cells using the M28z CAR. We found that intrapleurally administered CAR T cells vastly outperformed systemically infused T cells, requiring 30-fold fewer M28z T cells to induce long-term complete remissions.

Open revascularization procedures are more likely to influence smoking reduction than percutaneous procedures.

Background: Among patients with peripheral arterial disease (PAD), smokers have a higher incidence of life- and limb-threatening complications, including lower extremity ischemic rest pain, myocardial infarction, and cardiac death, highlighting the need for smoking reduction. Several studies have previously investigated the perioperative period as a teachable moment for smoking cessation. The purpose of this study is to determine whether the type of revascularization for PAD (percutaneous versus open) is associated with smoking reduction.

The role of preoperative positron emission tomography/computed tomography (PET/CT) in patients with high-risk melanoma.

Background: Positron emission tomography/computed tomography (PET/CT) scanning is commonly used for the preoperative staging of patients with at least intermediate thickness (>1 mm) melanomas. Its role in staging at initial diagnosis for clinically asymptomatic patients is not yet established.

Methods: We examined records of all patients receiving an operation for at least an intermediate thickness melanoma from June 2005 to June 2011.

A fair trial? Assessment of liver transplant candidates with psychiatric illnesses.

Allocating scarce organs to transplant candidates is only one stage in the long process of organ transplantation. Before being listed, all candidates must undergo a rigorous assessment by a multidisciplinary transplant team. The Department of Health and NHS Blood and Transplant (NHSBT) are responsible for the development of detailed strategies to ensure a fair and objective assessment experience for all transplant candidates.

Does the United States do it better? A comparative analysis of liver allocation protocols in the United Kingdom and the United States.

NHS Blood and Transplant (NHSBT) is responsible for the procurement and allocation of human organs in the United Kingdom. Its main role is to "ensure that organs donated for transplant are matched and allocated to patients in a fair and unbiased way." NHSBT’s liver allocation policies are underpinned by the National Liver Transplant Standards, a document published by the Department of Health in 2005 to oversee patient care, patient assessment, liver allocation and transplantation, education and training, and research and development.

Evaluation of alloreactivity in kidney transplant recipients treated with antithymocyte globulin versus IL-2 receptor blocker.

Induction therapy is used in kidney transplantation to inhibit the activation of donor-reactive T cells which are detrimental to transplant outcomes. The choice of induction therapy is decided based on perceived immunological risk rather than by direct measurement of donor T-cell reactivity. We hypothesized that immune cellular alloreactivity pretransplantation can be quantified and that blocking versus depleting therapies have differential effects on the level of donor and third-party cellular alloreactivity.