A novel small molecule Enpp1 inhibitor improves tumor control following radiation therapy by targeting stromal Enpp1 expression.

The uniqueness in each person's cancer cells and variation in immune infiltrates means that each tumor represents a unique problem, but therapeutic targets can be found among their shared features. Radiation therapy alters the interaction between the cancer cells and the stroma through release of innate adjuvants. The extranuclear DNA that can result from radiation damage of cells can result in production of the second messenger cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) by cyclic GMP-AMP synthase (cGAS).

Uncommon Anal Cancers.

Anal cancer is by itself a rare entity. Even rarer are the uncommon anal tumors described in this article. Diagnosis of these lesions can be challenging as some of these have no symptoms in their initial stages and only cause symptoms once they have progressed to advanced stages.

AGA Clinical Practice Update on Advances in Per-Oral Endoscopic Myotomy (POEM) and Remaining Questions-What We Have Learned in the Past Decade: Expert Review.

Description: This American Gastroenterological Association (AGA) Institute Clinical Practice Update (CPU) aims to review the available evidence and provide expert advice regarding advances in per-oral endoscopic myotomy (POEM).

Methods: This CPU was commissioned and approved by the AGA Institute CPU Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the CPU Committee and external peer review through standard procedures of Gastroenterology. This review is framed around best practice advice points agreed upon by the authors, based on the current available evidence and expert opinion in this field.

Intratumoral radiation dose heterogeneity augments antitumor immunity in mice and primes responses to checkpoint blockade.

Radiation therapy (RT) activates multiple immunologic effects in the tumor microenvironment (TME), with diverse dose-response relationships observed. We hypothesized that, in contrast with homogeneous RT, a heterogeneous RT dose would simultaneously optimize activation of multiple immunogenic effects in a single TME, resulting in a more effective antitumor immune response. Using high-dose-rate brachytherapy, we treated mice bearing syngeneic tumors with a single fraction of heterogeneous RT at a dose ranging from 2 to 30 gray.

Rapid metastatic recurrence after pancreatic cancer resection: a multi-center, regional analysis of trends in surgical failure over two decades.

Background: Pancreatic ductal adenocarcinoma (PDAc) is a lethal malignancy, attributed in part to high rates of rapid recurrence (rrPDAc) following resection. We sought to characterize recurrence rates over time and investigate factors predictive of rrPDAc.

Methods: A regional multi-institutional cancer registry, augmented with data from the National Surgical Quality Improvement Program database, was queried for patients with PDAc from 1996 to 2020.

North American Expert Consensus on the Post-procedural Care of Patients After Per-oral Endoscopic Myotomy Using a Delphi Process.

Background & Aims: There is significant variability in the immediate post-operative and long-term management of patients undergoing per-oral endoscopic myotomy (POEM), largely stemming from the lack of high-quality evidence. We aimed to establish a consensus on several important questions on the after care of post-POEM patients through a modified Delphi process.

Methods: A steering committee developed an initial questionnaire consisting of 5 domains (33 statements): post-POEM admission/discharge, indication for immediate post-POEM esophagram, peri-procedural medications and diet resumption, clinic follow-up recommendations, and post-POEM reflux surveillance and management.

Bone Cement in Adult Hip and Knee Reconstruction: A Review of Commercially Available Options and Clinical Outcomes.

Polymethyl-methacrylate (PMMA) bone cement is used extensively in hip and knee arthroplasty. A thorough understanding of the basic chemistry underlying PMMA is important for orthopaedic surgeons because this underscores the specific way bone cement is used during surgery. Recently, clinical research has shed light on the various types of PMMA regarding the viscosity of the mixture and the effect of cement additives.

Fluorescence tracking demonstrates T cell recirculation is transiently impaired by radiation therapy to the tumor.

T cells recirculate through tissues and lymphatic organs to scan for their cognate antigen. Radiation therapy provides site-specific cytotoxicity to kill cancer cells but also has the potential to eliminate the tumor-specific T cells in field. To dynamically study the effect of radiation on CD8 T cell recirculation, we used the Kaede mouse model to photoconvert tumor-infiltrating cells and monitor their movement out of the field of radiation.

Identifying predictors and determining mortality rates of septic cardiomyopathy and sepsis-related cardiogenic shock: A retrospective, observational study.

Introduction: Septic shock is a severe form of sepsis that has a high mortality rate, and a substantial proportion of these patients will develop cardiac dysfunction, often termed septic cardiomyopathy (SCM). Some SCM patients may develop frank cardiac failure, termed sepsis-related cardiogenic shock (SeRCS). Little is known of SeRCS.

Five-Year Outcomes from a Prospective Study on Safety and Efficacy of Phasix ST Mesh Use at the Hiatus During Paraesophageal Hernia Repair.

Background: Laparoscopic paraesophageal hernia (PEH) repair has a high hernia recurrence rate. The aim of this study was to assess the 5-year hernia recurrence rate after PEH repair using a combination of bioresorbable mesh and advanced surgical techniques to address tension as needed in a prospective group of patients.

Study Design: In 2016, a prospective database was established for 50 patients undergoing primary, elective PEH repair with a new bioresorbable mesh (Phasix ST).

Updated Markov Model to Determine Optimal Management Strategy for Patients with Paraesophageal Hernia and Symptoms, Cameron Ulcer, or Comorbid Conditions.

Background: The current paradigm of watchful waiting (WW) in people 65 years or older with an asymptomatic paraesophageal hernia (PEH) is based on a now 20-year-old Markov analysis. Recently, we have shown that elective laparoscopic hernia repair (ELHR) provides an increase in life-years (L-Ys) compared with WW in most healthy patients aged 40 to 90 years. However, elderly patients often have comorbid conditions and may have complications from their PEH such as Cameron lesions.

Preoperative CT and survival data for patients undergoing resection of colorectal liver metastases.

The liver is a common site for the development of metastases in colorectal cancer. Treatment selection for patients with colorectal liver metastases (CRLM) is difficult; although hepatic resection will cure a minority of CRLM patients, recurrence is common. Reliable preoperative prediction of recurrence could therefore be a valuable tool for physicians in selecting the best candidates for hepatic resection in the treatment of CRLM.

Defining the pathway to timely diagnosis and treatment of interstitial lung disease: a US Delphi survey.

Introduction: Timely diagnosis of interstitial lung disease (ILD) is limited by obstacles in the current patient pathway. Misdiagnosis and delays are common and may lead to a significant burden of diagnostic procedures and worse outcomes. This Delphi survey aimed to identify consensus on the key steps that facilitate the patient journey to an accurate ILD diagnosis and appropriate management in the US.

Patient experiences with SARS-CoV-2: Associations between patient experience of disease and coping profiles.

Introduction: Severe acute respiratory syndrome coronavirus 2, (SARS-CoV-2,) caused an influx of patients with acute disease characterized by a variety of symptoms termed COVID-19 disease, with some patients going on to develop post-acute COVID-19 syndrome. Individual factors like sex or coping styles are associated with a person's disease experience and quality of life. Individual differences in coping styles used to manage COVID-19 related stress correlate with physical and mental health outcomes.

Missed Opportunities: the Timing and Frequency of Screening Colonoscopy in Patients That Develop Esophageal Adenocarcinoma.

Introduction: Screening colonoscopy (SC) is widely accepted and has been shown to decrease the rate of colorectal cancer death. Guidelines and acceptance of screening for Barrett's esophagus (BE) are less established despite the fact that esophageal adenocarcinoma (EA) remains the fastest increasing cancer in the USA. The aim of this study was to assess the timing and frequency of SC in patients ultimately found to have EA and to evaluate the presence of symptoms and risk factors that might have prompted an esophagogastroduodenoscopy (EGD) and potentially earlier diagnosis of the EA.

Elective Laparoscopic Paraesophageal Hernia Repair Leads to an Increase in Life Expectancy Over Watchful Waiting in Asymptomatic Patients: An Updated Markov Analysis.

Objective: The aim of this study was to perform an updated Markov analysis to determine the optimal management strategy for patients with an asymptomatic paraesophageal hernia (PEH): elective laparoscopic hernia repair (ELHR) versus watchful waiting (WW).

Background: Currently, it is recommended that patients with an asymptomatic PEH not undergo repair based on a 20-year-old Markov analysis. The current recommendation might lead to preventable hospitalizations for acute PEH-related complications and compromised survival.

Tumor differentiation impacts response to neoadjuvant therapy and survival in patients with esophageal adenocarcinoma.

Objective: The current staging system for esophageal adenocarcinoma only considers tumor grade in early tumors. The aim of this study was to evaluate the impact of tumor differentiation on response to neoadjuvant chemoradiotherapy and survival in patients with locally advanced esophageal adenocarcinoma.

Methods: This was a multi-institution retrospective review of all patients with esophageal cancer who underwent neoadjuvant chemoradiotherapy followed by esophagectomy from January 2010 to December 2017.

Multicenter phase II trial of transanal total mesorectal excision for rectal cancer: preliminary results.

Background: Transanal TME (taTME) combines abdominal and transanal dissection to facilitate sphincter preservation in patients with low rectal tumors. Few phase II/III trials report long-term oncologic and functional results. We report early results from a North American prospective multicenter phase II trial of taTME (NCT03144765).

Impact of parental status on US medical student specialty selection.

Medical training occurs during peak childbearing years for most medical students. Many factors influence specialty selection. The aims of this study were (i) to determine whether being a parent is a major deciding factor when picking a specialty and (ii) whether parents are more drawn to family-friendly specialties than non-parents.

Randomized trial of gastric and colorectal endoscopic submucosal dissection defect closure comparing a novel through-the-scope suturing system with an over-the-scope suturing system (with video).

Background And Aims: Mucosal closure adds time but reduces adverse events associated with endoscopic submucosal dissection (ESD). We aimed to assess the closure time (CT), technical success, and cost-effectiveness between a novel through-the-scope helix tack suture system (TTSS) and the over-the-scope suturing system (OTSS).

Methods: In this single-center, prospective, randomized trial, all patients undergoing ESD with anticipated closure were randomized 1:1 to TTSS (study group) or OTSS (control group).

Diaphragmatic relaxing incisions for complex hiatal reconstruction: longer-term follow-up confirms safety, efficacy and rare complications.

Background: Tension is an important factor in hernia repairs. Relaxing incisions to reduce tension are common with ventral hernia repairs, and techniques for relaxing incisions also exist for the hiatus. The aim of this study was to update our original experience with a diaphragm relaxing incision (DRI) in a larger group of patients with longer follow-up.