Predicting Survival in Mucinous Adenocarcinoma of the Appendix: Demographics, Disease Presentation, and Treatment Methodology.

BACKGROUND: Mucinous adenocarcinoma of the appendix (MACA) follows a complex disease course with variable survival. Large-scale predictive modeling may determine subtle yet important prognostic factors otherwise unseen in smaller cohort analyses. METHODS: Patients with MACA were identified from the Surveillance, Epidemiology, and End Results (SEER) Research Plus database (2005-2019). Primary, secondary, and tertiary outcomes were disease-specific survival (DSS), overall survival (OS), and average annual percent change (AAPC) in incidence. RESULTS: Among 4,258 included patients, MACA was most frequently diagnosed at 50 to 69 years (52.0%), with female preponderance (55.9%). MACA incidence AAPC was 3.8 (95% confidence interval [CI] 1.9-5.9). For patients with exclusive, first-diagnosis MACA included in survival analysis (3,222 patients), median DSS and OS were 118 and 88 months, respectively. In DSS-based multivariable analysis, worse prognosis was associated with non-Hispanic Black background (HR 1.36, 95% CI 1.02-1.82; p = 0.036), high grade (grade 3 HR 3.10, 95% CI 2.44-3.92; p < 0.001), lymphatic spread (HR 2.73, 95% CI 2.26-3.30; p < 0.001), and distant metastasis (HR 5.84, 95% CI 3.86-8.83; p < 0.001). In subcohort analysis of patients with rationale for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC, 2,387 patients), CRS-HIPEC was associated with survival benefit compared with surgery alone but only for moderate-grade tumors (median DSS/OS 138/138 vs. 116/87 months; p < 0.001). CONCLUSIONS: Mucinous adenocarcinoma of the appendix incidence is increasing in the United States. Survival rates are affected by both demographics and classical risk factors, and CRS-HIPEC-associated survival benefit predominantly occurs in moderate-grade tumors. Further exploration of biologic and clinicopathologic features may enhance risk stratification for this disease.

Factors Associated With Early Motor Function Trajectories in DMD After Glucocorticoid Initiation: Post Hoc Analysis of the FOR-DMD Trial.

BACKGROUND AND OBJECTIVES: Clinical trials in Duchenne muscular dystrophy (DMD) require 3-6 months of stable glucocorticoids, and the primary outcome is explored at 48-52 weeks. The factors that influence the clinical outcome assessment (COA) trajectories soon after glucocorticoid initiation are relevant for the design and analysis of clinical trials of novel drugs. We describe early COA trajectories, associated factors, and the time from glucocorticoid initiation to COA peak. METHODS: This was a prospective 18-month analysis of the Finding the Optimum Corticosteroid Regimen for Duchenne Muscular Dystrophy study. Four COAs were investigated: rise from supine velocity (RFV), 10-meter walk/run velocity (10MWRV), North Star Ambulatory Assessment (NSAA) total score, and 6-minute walk test distance (6MWT). The relationships of baseline age (4-5 vs 6-7 years), COA baseline performance, genotype, and glucocorticoid regimen (daily vs intermittent) with the COA trajectories were evaluated using linear mixed-effects models. RESULTS: One hundred ninety-six glucocorticoid-naïve boys with DMD aged 4-7 years were enrolled. The mean age at baseline was 5.9 ± 1.0 years, 66% (n = 130) were on daily regimens, 55% (n = 107) showed a 6MWT distance >330 metres; 41% (n = 78) showed RFV >0.2 rise/s; 76% (n = 149) showed 10MWRV >0.142 10m/s, and 41.0% (n = 79) showed NSAA total score >22 points. Mean COA trajectories differed by age at glucocorticoid initiation (p < 0.01 for RFV, 10MWRV, and NSAA; p < 0.05 for 6MWT) and regimen (p < 0.01 for RFV, 10MWRV, and NSAA). Boys younger than 6 years reached their peak performance 12-18 months after glucocorticoid initiation. Boys aged 6 years or older on a daily regimen peaked between months 9 and 12 and those on an intermittent regimen by 9 months. The baseline COA performance was associated with the NSAA (p < 0.01) and the 6MWT trajectory in boys younger than 6 years on a daily regimen (p < 0.01). Differences in the mean trajectories by genotype were not significant. DISCUSSION: Glucocorticoid regimen, age, duration of glucocorticoid exposure, and baseline COA performance need to be considered in the design and analysis of clinical trials in young boys with DMD.

The Gut Microbiome Controls Liver Tumors via the Vagus Nerve.

Liver cancer ranks amongst the deadliest cancers. Nerves have emerged as an understudied regulator of tumor progression. The parasympathetic vagus nerve influences systemic immunity via acetylcholine (ACh). Whether cholinergic neuroimmune interactions influence hepatocellular carcinoma (HCC) remains uncertain. Liver denervation via hepatic vagotomy (HV) significantly reduced liver tumor burden, while pharmacological enhancement of parasympathetic tone promoted tumor growth. Cholinergic disruption in Rag1KO mice revealed that cholinergic regulation requires adaptive immunity. Further scRNA-seq and in vitro studies indicated that vagal ACh dampens CD8+ T cell activity via muscarinic ACh receptor (AChR) CHRM3. Depletion of CD8+ T cells abrogated HV outcomes and selective deletion of Chrm3 on CD8 + T cells inhibited liver tumor growth. Beyond tumor-specific outcomes, vagotomy improved cancer-associated fatigue and anxiety-like behavior. As microbiota transplantation from HCC donors was sufficient to impair behavior, we investigated putative microbiota-neuroimmune crosstalk. Tumor, rather than vagotomy, robustly altered fecal bacterial composition, increasing Desulfovibrionales and Clostridial taxa. Strikingly, in tumor-free mice, vagotomy permitted HCC-associated microbiota to activate hepatic CD8+ T cells. These findings reveal that gut bacteria influence behavior and liver anti-tumor immunity via a dynamic and pharmaceutically targetable, vagus-liver axis.

CDH1 and hereditary diffuse gastric cancer: a narrative review.

BACKGROUND AND OBJECTIVE: Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant cancer syndrome that increases lifetime risk of diffuse-type gastric cancer which carries a dismal overall survival. Due to the high prevalence of cancer in patients with CDH1 variants, early screening and prophylactic total gastrectomy (PTG) are recommended. This review aims to summarize the current understanding of CDH1 and HDGC, highlighting its molecular and cellular implications as well as its clinical management and research efforts. METHODS: A review of PubMed and ClinicalTrials.gov was conducted. Articles published in English and with full text were considered. PubMed was searched using the terms 'CDH1' AND 'Hereditary Diffuse Gastric Cancer'. KEY CONTENT AND FINDINGS: Loss-of-function mutations in the CDH1 gene, which encodes the cell adhesion protein E-cadherin, have been identified as the primary cause of HDGC. The loss of E-cadherin expression disrupts cell-cell adhesion and activates oncogenic signaling pathways, ultimately promoting cancer cell growth and dissemination. Prophylactic total gastrectomy (PTG) is recommended for pathogenic CDH1 variant carriers with a family history of diffuse gastric cancer (DGC). However, recent studies of endoscopic surveillance utilizing specific biopsy protocols have demonstrated the potential for surveillance as an alternative to total gastrectomy in selected patients. Researchers are actively investigating the consequences of E-cadherin loss in gastric epithelium and have identified potential molecular drivers of HDGC development using animal models and organoids. These discoveries provide promise for chemoprevention strategies, biomarker discovery, and targeted therapies for diffuse-type gastric cancer. CONCLUSIONS: The understanding of HDGC has significantly advanced in recent years, with the loss of E-cadherin expression identified as a crucial factor in disease pathogenesis. The use of advanced in vitro models offers substantial promise for investigating the molecular mechanisms underlying HDGC and identifying novel therapeutic targets. By leveraging advanced models, continuing clinical trials, and improving clinical management of affected individuals, researchers can work towards the development of more effective treatment strategies for HDGC. The goal is to prevent cancers from developing in patients with CDH1 gene variants and minimize the burden of cancer.

Review of Traumatic Duodenal Injuries: Etiology, Diagnosis, and Management.

Traumatic duodenal injuries are rare and often challenging to diagnose and treat. Management of these injuries remains controversial and continues to evolve. Here, we performed a review of the literature and guidelines for the diagnosis and management of traumatic duodenal injuries.A common recommendation in more recent literature is primary, tension-free repair of duodenal injuries when possible if surgical repair is necessary. Conversely, if duodenal injuries are unamenable to primary repair, more complex procedures such as Roux-en-Y duodenojejunostomy or pancreaticoduodenectomy may be necessary. Regardless of injury grade or type of surgical repair, the literature continues to support wide extraluminal drainage. Over time, the management of complex duodenal injuries has evolved to favor simple primary repair whenever possible. According to recent studies, more complex procedures are associated with higher rates of post-operative complications and should be reserved for severe injuries when primary repair is not possible.

Desmoid-type fibromatosis in the setting of malignant peritoneal mesothelioma: a case report of two rare diseases.

BACKGROUND: Desmoid-type fibromatosis (DTF) is a rare benign lesion that usually arises from the abdominal wall or extremities and rarely from the mesentery or intrabdominal organs. Malignant peritoneal mesothelioma is also a rare, yet aggressive disease. To our knowledge, this is the first case report of desmoid-type fibromatosis in the setting of malignant peritoneal mesothelioma. CASE PRESENTATION: An early 30-year-old female was referred to our center for large intra-abdominal mass concerning for recurrent malignant peritoneal mesothelioma after previous cytoreductive surgery with hyperthermic intraperitoneal chemotherapy and adjuvant chemotherapy. Further investigation revealed a large mesenteric mass, which was resected en bloc with the cecum and terminal ileum. Pathologic findings confirmed a surprising diagnosis of desmoid-type fibromatosis. CONCLUSIONS: No adjuvant therapy was offered to this patient due to negative tumor margins; however, close follow-up will be provided for recurrence of both malignant peritoneal mesothelioma and desmoid-type fibromatosis, which can be differentiated in the future via biopsy in this patient.

Malignant peritoneal mesothelioma literature review: past, present, and future.

Background and Objective: Malignant peritoneal mesothelioma (MPM) is an insidious neoplasm that arises from the mesothelial lining of the abdominal cavity. Historically, outcomes of MPM were dismal, as MPM is relatively resistant to cytotoxic chemotherapy. However, with advances in technology and improved understanding of tumor pathophysiology, treatments for MPM have produced encouraging 5-year survival. The standard of care for patients with resectable disease remains cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Patients with inoperable MPM can be offered several systemic treatments, including chemotherapy, immune checkpoint inhibitors, or investigational treatments. Our objective is to provide an overview of our current knowledge concerning MPM and latest advances in treatment. Methods: Narrative overview of the literature published in English from database origin until January 31, 2022 relating to MPM was searched in PubMed database, Google Scholar, and ClinicalTrials.gov. Key Content and Findings: CRS-HIPEC has offered improved survival for surgical candidates, however outcomes for inoperable MPM remains dismal. With advancements in technology and better understanding of underlying MPM biology, new treatment approaches are arising and imperative. Conclusions: MPM is a rare and lethal disease of the peritoneum. CRS-HIPEC remains the standard of care for resectable disease. In 2022, several clinical trials are available for patients with MPM offering future advances in therapy and further understanding of this rare disease process.

Adjuvant chemotherapy is associated with improved overall survival in select patients with Stage II colon cancer: A National Cancer Database analysis.

BACKGROUND AND OBJECTIVES: Guidelines for Stage II colon cancer recommend adjuvant chemotherapy (AC) only for tumors with high-risk features, but long-term outcomes data are mixed. We aimed to determine if AC was associated with a survival benefit in this population. METHODS: Patients were identified from the National Cancer Database and included if they met the following criteria: diagnosis of Stage II colon cancer, surgery, survival data, and complete data on six high-risk features. The cohort of 57 335 patients was stratified by receipt of AC. Subgroup analysis was performed on patients under the age of 65 years with no comorbidities. Overall survival (OS) was the primary endpoint. RESULTS: An increasing number of high-risk features was associated with significantly decreased median OS. AC was associated with significantly increased OS for patients with 0, 1, 2, and ≥3 high-risk features. On subgroup analysis, receipt of AC was associated with a reduced risk of death (hazard ratio: 0.66; confidence interval: 0.59-0.74). For patients in the subgroup who had a T4 tumor, AC was associated with increased OS (92.7 vs. 83.6 months). CONCLUSIONS: AC should be considered for all younger, healthy patients with Stage II colon cancer and may be associated with a survival benefit for patients with T4 disease.

Safety, efficacy, and tolerability of immune checkpoint inhibitors in the treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a major cause of mortality worldwide with an increasing incidence due to escalating rates of obesity and non-alcoholic fatty liver disease. Unfortunately, a majority of patients with HCC present with advanced disease. The immune checkpoint inhibitor atezolizumab, a PD-L1 inhibitor, in combination with bevacizumab, anti-VEGF, has become the new standard of care for patients with advanced HCC after demonstrating improved overall and progression free survival over sorafenib. In this review, we discuss the evolving role of immune checkpoint inhibitors in the treatment of HCC and their safety, efficacy, and tolerability.

Clinical and Genetic Characteristics in Young, Glucocorticoid-Naive Boys With Duchenne Muscular Dystrophy.

BACKGROUND AND OBJECTIVES: Duchenne muscular dystrophy (DMD) is a paediatric neuromuscular disorder caused by mutations in the dystrophin gene. Geneotype-phenotype associations have been examined in glucocorticoid treated boys, but there are few data on the young glucocorticoid-naïve DMD population. A sample of young glucocorticoid-naïve DMD boys is described and genotype-phenotype associations are investigated. METHODS: Screening and baseline data were collected for all the participants in the Finding the Optimum Corticosteroid Regime for Duchenne Muscular Dystrophy (FOR-DMD)study, an international, multi-centre, randomized, double-blind, clinical trial comparing three glucocorticoid regimens in glucocorticoid-naïve, genetically confirmed boys with DMD between 4 and <8 years of age. RESULTS: One hundred and ninety-six boys were recruited. The meanage at randomization (+ standard deviation) was 5.8+ 1.0 years. The predominant mutation type was out of frame deletions 67.4%, (130/193) of which 68.5% (89/130) were amenable to exon skipping. The most frequent mutations were deletions amenable to exon 51 skipping 13.0% (25/193). Stop codon mutations accounted for 10.4% (20/193).The mean age at first parental concerns was 29.8 + 18.7 months, the mean age at genetic diagnosis was 53.9 + 21.9 months and the mean diagnostic delay was 25.9 + 18.2 months. The mean diagnostic delay for boys diagnosed following an incidental finding of isolated hyperCKemia (n=19) was 6.4 + 7.4 months. The mean ages at independent walking and talking in sentences were 17.1 + 4.2 and 29.0 + 10.7 months, respectively. Median height percentiles were below the 25th percentile regardless of age group. No genotype-phenotype associations were identified expect for boys with an exon 8 skippable deletions who had better performance on time to walk/run 10 meters (p=0.02)compared to boys with deletions not amenable to skipping. DISCUSSION: This study describes clinical and genetic characteristics of a sample of young glucocorticoid-naïve boys with DMD. A low threshold for CK testing can lead to an earlier diagnosis. Motor and speech delay were common presenting symptoms.The effects of low, pre-treatment height on growth and adults height requires further study. These findings may promote earlier recognition of DMD and inform study design for future clinical trials.

Novel Therapies in Oncology: An Individualized Approach.

For decades, oncology treatments revolved around chemotherapeutic regimens that have been relatively nonspecific in their approach to cancer cell death. With advancements in genomics and personalized medicine, however, knowledge of the immune system has dramatically increased and methods for treating cancers have become much more individualized. With this increase in knowledge, vast arrays of novel therapies have entered the oncology realm. Nurses are expected to administer these therapies and ultimately manage the resulting toxicities and side effects. Such effects sometimes lead to severe illness, which may require intensive care unit admission. This article reviews novel therapies in oncology and nursing considerations pertaining to these treatment approaches as they relate to solid tumors.

A discussion of the gut microbiome's development, determinants, and dysbiosis in cancers of the esophagus and stomach.

The microbiome refers to a population of microbes that colonize the skin, nasopharynx, oral cavity, gastrointestinal tract, and urogenital tract. The human microbiome consists of bacteria, archaea, fungi, viruses, and phages. Recent advances in genomic sequencing have catalyzed a deeper understanding of complex microbe-microbe and host-microbe interactions. Dysregulation of these interactions, or dysbiosis of the gastrointestinal tract, has been implicated in a growing list of pathologies including nonalcoholic fatty liver disease, cardiovascular disease, obesity, diabetes, depression, Parkinson's disease, autism, and various gastrointestinal cancers. Gastric and esophageal cancer, for example, continue to remain as two of the most common causes of cancer-related deaths worldwide, therefore there is an increased emphasis on investigating the role of dysbiosis on these cancers. In this review, we discuss the development and structure of the gut microbiome, its homeostatic and dysbiotic mechanisms, and the key microbes in esophageal and gastric carcinogenesis with a focus on bacterial biology. Further clarification of these pathways and discovery of diagnostic or therapeutic targets could have broad impacts on global subpopulations. It is important to understand the nature of the gastrointestinal tract microbiome and its potentional risk factors for dysbiosis in order to tailor its application to the individual patient and create an era of highly personalized, precision medicine.

Assessing the immediate impact of COVID-19 on surgical oncology practice: Experience from an NCI-designated Comprehensive Cancer Center in the Northeastern United States.

BACKGROUND: The effects of the coronavirus disease 2019 (COVID-19) pandemic on surgical oncology practice are not yet quantified. The aim of this study was to measure the immediate impact of COVID-19 on surgical oncology practice volume. METHODS: A retrospective study of patients treated at an NCI-Comprehensive Cancer Center was performed. "Pre-COVID" era was defined as January-February 2020 and "COVID" as March-April 2020. Primary outcomes were clinic visits and operative volume by surgical oncology subspecialty. RESULTS: Abouyt 907 new patient visits, 3897 follow-up visits, and 644 operations occurred during the study period. All subspecialties experienced significant decreases in new patient visits during COVID, though soft tissue oncology (Mel/Sarc), gynecologic oncology (Gyn/Onc), and endocrine were disproportionately affected. Telehealth visits increased to 11.4% of all visits by April. Mel/Sarc, Gyn/Onc, and Breast experienced significant operative volume decreases during COVID (25.8%, p = 0.012, 43.6% p < 0.001, and 41.9%, p < 0.001, respectively), while endocrine had no change and gastrointestinal oncology had a slight increase (p = 0.823) in the number of cases performed. CONCLUSIONS: The effects of the COVID-19 pandemic are wide-ranging within surgical oncology subspecialties. The addition of telehealth is a viable avenue for cancer patient care and should be considered in surgical oncology practice.

Adult Acute Lymphoblastic Leukemia: Treatment and Management Updates.

OBJECTIVE: To present an overview of novel therapies for the treatment of adult acute lymphoblastic leukemia and to discuss nursing implications for these new therapies. DATA SOURCES: Published manuscripts, Web sites, and pharmaceutical package inserts. CONCLUSION: Several promising therapies have emerged in the treatment of relapsed/refractory and minimal residual disease acute lymphoblastic leukemia. IMPLICATIONS FOR NURSING PRACTICE: With the changing paradigm for hematologic malignancies, nurses must remain current in their knowledge regarding novel therapies, including their administration, toxicity profile, and management of adverse events. This article addresses the clinical benefits of novel agents and nursing implications for those agents.