The HER2 flip-HER2 amplification of tumor cells in the cerebrospinal fluid of breast cancer patients with leptomeningeal disease: implications for treating the LM tumor with anti-HER2 therapy.

Introduction: CNSide is a platform that detects and characterizes tumor cells in the cerebrospinal fluid (CSF) of patients with leptomeningeal disease (LMD). The platform was validated per College of American Pathologists (CAP) and Clinical Laboratories Improvement Amendment (CLIA) guidelines and run as a commercial Laboratory Developed Test (LDT) at Biocept in San Diego, CA. The platform allows CSF tumor cell (CSF-TC) enumeration and biomarker characterization by fluorescent in situ hybridization (FISH). Methods: We performed a multicenter retrospective chart review of HER2 FISH CNSide test results that were commercially ordered on 26 patients by physicians for LMD breast cancer patients between April 2020 and October 2022. Results: We show that HER2 is amplified on CSF tumor cells in 62% (16/26) of LMD breast cancer patients. 10/26 (38%) patients had discordant HER2-positivity between the primary tumor tissue and CSF-TC; of these, 35% (9/26) of the patients displayed HER2 amplification on the CSF-TCs, however were categorized as HER2 negative on the primary tumor. Of the 27% (7/26) patients with a HER2 positive primary tumor, one patient showed a HER2 negative LMD tumor. Two patients, 8% (2/26) had a HER2 equivocal primary tumor; of these, one demonstrated a HER2 negative, and one a HER2 positive LMD tumor. Serial analysis (at least 4 longitudinal tests) of HER2 status of the CSF-TC throughout therapy was available for 14 patients and demonstrated that HER2 status of the LMD changed in 29% (4/14) during their treatment course and impacted care decisions. Conclusions: Our data suggests that CSF-TC HER2 FISH analysis in LMD breast cancer patients may be discordant to the primary tumor sample and the discovery of HER2 positivity in the CSF may open doors to anti-HER2 targeted therapy options for LMD patients.

Extraneural metastatic ependymoma: distant metastasis to the pleura, lungs, lymph nodes and bone.

Ependymomas are neuroepithelial tumours arising from ependymal cells surrounding the cerebral ventricles that rarely metastasise to extraneural structures. This spread has been reported to occur to the lungs, lymph nodes, liver and bone. We describe the case of a patient with recurrent CNS WHO grade 3 ependymoma with extraneural metastatic disease. He was treated with multiple surgical resections, radiation therapy and salvage chemotherapy for his extraneural metastasis to the lungs, bone, pleural space and lymph nodes.

The Population-level Prevalence of Exocrine Pancreas Insufficiency and the Subsequent Risk of Pancreatic Cancer.

OBJECTIVES: To study the prevalence of exocrine pancreas insufficiency (EPI) at a population level and the subsequent risk of pancreatic ductal adenocarcinoma (PDAC). METHODS: Using TriNetX (a database of over 79 million US residents), we included patients ≥18 years with EPI (identified via ICD-10 codes) and continuous follow-up from 2016-2022. Patients with prior pancreas resection and PDAC before an EPI diagnosis were excluded. The primary outcome was EPI prevalence. Secondary outcomes included imaging utilization, PDAC risk and, pancreas enzyme replacement therapy (PERT) utilization. We performed 1:1 propensity score matching of patients with EPI vs. patients without an EPI diagnosis. Adjusted odds ratio (aOR) and hazard ratios (aHR) with 95% confidence intervals were reported. RESULTS: The population prevalence of EPI was 0.8% (n = 24,080) with a mean age of 55.6 years at diagnosis. After propensity score matching, PDAC risk among patients with EPI was twice as high compared to patients without EPI (AHR 1.97, 95% confidence interval [CI] 1.66-2.36). This risk persisted even after excluding patients with a history of acute or chronic pancreatitis (aOR: 4.25, 95% CI 2.99-6.04). Only 58% (n = 13, 390) of patients with EPI received PERT with a mean treatment duration of 921 days. No difference was observed in PDAC risk between patients with EPI treated with PERT vs. those that did not receive PERT (AHR 1.10, 95% CI 0.95-1.26, p = 0.17). CONCLUSIONS: Despite a low prevalence, patients with EPI may have a higher risk of PDAC and many of these patients with EPI were not on PERT. PERT did not appear to impact incident PDAC risk after an EPI diagnosis.

Work Productivity Impairment in Persons with Inflammatory Bowel Diseases: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: The impact of inflammatory bowel disease (IBD) on work productivity remains unclear. In this systematic review and meta-analysis, we quantify work-related outcomes and employment data among persons with IBD. METHODS: A systematic literature search was conducted in MEDLINE, EMBASE, the Cochrane library, Scopus, ProQuest, and clinicaltrials.gov from inception to February 2023 to identify studies on work productivity in persons with IBD aged >18 years. Work productivity was defined primarily by the Work Productivity and Activity Impairment (WPAI) questionnaire which includes absenteeism, presenteeism, overall work impairment, and non-work activity impairment. In addition, we included data on employment, sick leaves, disability pensions, and indirect costs due to productivity loss. Pooled effect analysis was conducted using a random-effects model for pooled estimates of continuous and proportional data with 95% confidence intervals. RESULTS: Among all patients with IBD, the pooled estimates were 16.4% for absenteeism, 35.9% for presenteeism, 39.4% for overall work impairment, and 46.0% for non-work activity impairment. Indirect costs from overall work impairment were 5,131.09 euros/patient/year. Only two thirds of IBD patients were employed and 1 in 3 patients lost their jobs due to IBD. Among those employed, 39.5% report sick days, 21.3% report work disability, and 12.3% receive disability pensions. Most studies demonstrate clinically meaningful improvements in work productivity with medical and/or surgical therapies. CONCLUSION: Persons with IBD experience significant work impairment and associated indirect costs. This highlights the need for appropriate workplace accommodations and timely medical therapy to alleviate the burden of disease and improve work outcomes.

Endoscopic submucosal dissection (ESD) outcomes in T1B esophageal cancer: a retrospective study.

BACKGROUND AND AIMS: The role of submucosal endoscopic dissection (ESD) in management of invasive esophageal cancer (EC) remains unclear. In this case series, we evaluate the clinical and technical outcomes of patients who underwent ESD with pathologically staged T1b EC. METHODS: This retrospective study included patients who underwent ESD between December 2016 and April 2023 with pathologically staged T1b EC. Patient demographics, tumor characteristics, and ESD technical outcomes were analyzed. Patients were followed to determine disease-free survival and tumor recurrence rates. RESULTS: Sixteen patients with a total of 17 pathologically staged T1b ECs were included in this case series with a median follow-up time of 28 months [range 3-75]. ESD had high en-bloc (100%) and R0 (82.3%) resection rates. 16/17 patients (94.1%) were discharged the same day, and there were no immediate perioperative complications. 4/17 patients (23.5%) had curative ESD resections with no tumor recurrence. Among those with non-curative resections (n = 13), 5 patients had ESD only, 6 had ESD + surgery, and 2 underwent ESD + chemoradiation. In the ESD only group, 2/5 patients (40%) had tumor recurrence. In the ESD + surgery group, one patient died from a surgical complication, and 1/5 (20%) had tumor recurrence at follow-up. There was no tumor recurrence among patients who had ESD + chemoradiation. CONCLUSION: ESD is safe with high en-bloc and R0 resection rates in T1b EC. Recurrence rates are low but patients need close monitoring. Larger-scale studies are needed to determine the long-term clinical efficacy of ESD in T1b EC.

Inflammatory Bowel Disease and Breastfeeding: A Narrative Review.

Inflammatory bowel disease (IBD) frequently affects women of childbearing age who may consider breastfeeding. Although breastfeeding has numerous benefits, there remain concerns regarding the safety of breastfeeding among women with IBD. Breastfeeding is important in developing the immune system of infants and has been shown to protect against the development of IBD. The risk of developing an increase in disease activity postpartum is the same regardless of breastfeeding status. Most IBD medications are also considered safe in breastfeeding and have no major risks to infants. Despite this, breastfeeding rates remain low among women with IBD, mostly due to concerns about the safety of IBD therapy with breastfeeding. Many women self-discontinue their IBD medications to breastfeed, and there is often uncertainty among health professionals to make recommendations about therapy. Dedicated IBD clinics can greatly support mothers during pregnancy and breastfeeding periods to enhance their knowledge, optimize their medication adherence, and improve their postpartum outcomes. This review aims to provide the most recent evidence-based literature regarding the safety of breastfeeding in women with IBD and the current recommendations about medical therapies with breastfeeding.

The literature supports breastfeeding as a generally safe and beneficial practice for mothers with inflammatory bowel disease, though misconceptions around the safety of this practice persist. Multidisciplinary care models are essential for improving outcomes for women with inflammatory bowel disease who are breastfeeding.