Discectomy for Lumbar Disc Herniation in Pediatric and Adolescent Populations: A Systematic Review and Meta-Analysis.

Corroborative evidence for discectomy in pediatric or adolescent patients remains scarce, with this single-arm meta-analysis investigating discectomy for lumbar disc herniation (LDH) within this population. PubMed, Embase (Elsevier), CiNAHL, Cochrane Library, Scopus, and Web of Science were searched. Eligible studies reported pediatric patients under 21 years of age with a diagnosis of LDH that was treated surgically with discectomy. This review was registered in PROSPERO (ID: CRD42023463358). Twenty-two studies met the eligibility criteria (n=1182). Visual analog scale (VAS) scores for back pain at baseline were 5.34 (95% CI: 4.48, 6.20, I2=98.9%). Postoperative VAS back pain scores after 12 months were 0.88 (95% CI: 0.57, 1.19, I2=95.6%). VAS scores for leg pain at baseline were 7.03 (95% CI: 6.63, 7.43, I2=93.5%). Postoperative VAS leg pain scores after 12 months were 1.02 (95% CI: 0.68, 1.36, I2=97.0%). Oswestry disability index (ODI) scores at baseline were 55.46 (95% CI: 43.69, 67.24, I2=99.9%). Postoperative ODI scores after 12 months were 7.82 (95% CI: 4.95, 10.69, I2=99.4%). VAS back, VAS leg and ODI scores demonstrated a minimum clinically important difference (MCID) at all postoperative points. Perioperative outcomes demonstrated operative time as 85.71 mins (95% CI: 73.96, 97.46, I2=99.4%) and hospital length of stay as 3.81 days (95% CI: 3.20, 4.41, I2=98.5%). The postoperative reoperation rate at the same level was 0.01 (95% CI: <0.00, 0.02, I2=0%). Discectomy appears safe and effective in pediatric and adolescent patients suffering from LDH. The findings here provide groundwork for future randomized control trials against conservative measures to elaborate on optimal management and elucidate long-term outcomes.

Multi-omic profiling of intraductal papillary neoplasms of the pancreas reveals distinct expression patterns and potential markers of progression.

In order to advance our understanding of precancers in the pancreas, 69 pancreatic intraductal papillary neoplasms (IPNs), including 64 intraductal papillary mucinous neoplasms (IPMNs) and 5 intraductal oncocytic papillary neoplasms (IOPNs), 32 pancreatic cyst fluid samples, 104 invasive pancreatic ductal adenocarcinomas (PDACs), 43 normal adjacent tissues (NATs), and 76 macro-dissected normal pancreatic ducts (NDs) were analyzed by mass spectrometry. A total of 10,246 proteins and 22,284 glycopeptides were identified in all tissue samples, and 756 proteins with more than 1.5-fold increase in abundance in IPMNs relative to NDs were identified, 45% of which were also identified in cyst fluids. The over-expression of selected proteins was validated by immunolabeling. Proteins and glycoproteins overexpressed in IPMNs included those involved in glycan biosynthesis and the immune system. In addition, multiomics clustering identified two subtypes of IPMNs. This study provides a foundation for understanding tumor progression and targets for earlier detection and therapies. Significance: This multilevel characterization of intraductal papillary neoplasms of the pancreas provides a foundation for understanding the changes in protein and glycoprotein expression during the progression from normal duct to intraductal papillary neoplasm, and to invasive pancreatic carcinoma, providing a foundation for informed approaches to earlier detection and treatment.

Long-Duration Neoadjuvant Therapy with FOLFIRINOX Yields Favorable Outcomes for Patients Who Undergo Surgery for Pancreatic Cancer.

BACKGROUND: In 2023 alone, it's estimated that over 64,000 patients will be diagnosed with PDAC and more than 50,000 patients will die of the disease. Current guidelines recommend neoadjuvant therapy for patients with borderline resectable and locally advanced PDAC, and data is emerging on its role in resectable disease. Neoadjuvant chemotherapy may increase the number of patients able to receive complete chemotherapy regimens, increase the rate of microscopically tumor-free resection (R0) margin, and aide in identifying unfavorable tumor biology. To date, this is the largest study to examine surgical outcomes after long-duration neoadjuvant chemotherapy for PDAC. METHODS: Retrospective analysis of single-institution data. RESULTS: The routine use of long-duration therapy in our study (median cycles: FOLFIRINOX = 10; gemcitabine-based = 7) is unique. The majority (85%) of patients received FOLFIRINOX without radiation therapy; the R0 resection rate was 76%. Median OS was 41 months and did not differ significantly among patients with resectable, borderline-resectable, or locally advanced disease. CONCLUSIONS: This study demonstrates that in patients who undergo surgical resection after receipt of long-duration neoadjuvant FOLFIRINOX therapy alone, survival outcomes are similar regardless of pretreatment resectability status and that favorable surgical outcomes can be attained.

Diagnostic approach to hepatic vascular lesions: a paediatric perspective.

The pathological evaluation of hepatic vascular lesions in children requires special consideration. Inconsistent terminology, rarity of pathology specimens and overlapping pathological features between various lesions may pose a serious diagnostic challenge. In this review, we highlight the importance of using the International Society for the Study of Vascular Anomalies (ISSVA) classification scheme to characterise these lesions. Selected entities are discussed, including hepatic vascular tumours exclusively seen in the paediatric age group, hepatic infantile haemangioma and hepatic congenital haemangioma. Vascular malformations, with emphasis on their syndromic associations (venous malformation in blue rubber bleb naevus syndrome) and complications (hepatocellular nodules in Abernethy malformation) are also covered.

Transcatheter Arterial Radioembolization-Induced Gastric Ulcer in an Excluded Stomach After Roux-en-Y Gastric Bypass.

Transcatheter arterial radioembolization (TARE) is a common locoregional treatment for hepatocellular carcinoma. It is associated with peptic ulcer disease in up to 5% of patients. A 70-year-old man with Roux-en-Y gastric bypass and liver cirrhosis with hepatocellular carcinoma treated with TARE 6 months earlier was evaluated for continued melena and was found to have an ulcer in the excluded stomach. This was successfully treated with liquid proton pump inhibitor through gastrostomy tube to the excluded stomach. This represents a unique case of successful management of TARE-induced peptic ulcer disease in the excluded stomach of a Roux-en-Y gastric bypass patient.

Clinical outcomes of outpatient thyroidectomy: A systematic review and single-arm meta-analysis.

BACKGROUND: The aim of this meta-analysis is to investigate the safety of outpatient thyroidectomy based on 24-h and same-day discharge criteria. METHODS: CENTRAL, Embase, PubMed, and Scopus were searched. A meta-analysis of selected studies was performed. The review was registered prospectively with PROSPERO (CRD42022361134). RESULTS: Thirty-one studies met the eligibility criteria, with a total of 74328 patients undergoing thyroidectomy in an outpatient setting based on 24-h discharge criteria. Overall postoperative complications after outpatient thyroidectomies were 5.7% (95%CI: 0.049-0.065; I2 â€‹= â€‹97.3%), consisting of hematoma (0.4%; 95%CI: 0.003-0.005; I2 â€‹= â€‹83.4%), recurrent laryngeal nerve injury (0.4%; 95%CI: 0.003-0.006; I2 â€‹= â€‹93.5%), and hypocalcemia (1.6%; 95%CI: 0.012-0.019; I2 â€‹= â€‹93.7%). The rate of readmission was 1.1% (95%CI: 0.007-0.015; I2 â€‹= â€‹95.4%). Results were similar for same-day criteria. CONCLUSIONS: Our analysis demonstrated that outpatient thyroidectomy is a safe procedure in the management of thyroid disease for selected patients.

Delays in definitive endoscopic resection of previously manipulated colorectal polyps as a risk factor for inferior resection outcomes.

BACKGROUND AND AIMS: Manipulation of colorectal polyps by biopsy, incomplete resection, or tattoo placement under the lesion has been shown to cause submucosal fibrosis and associated inferior outcomes. The effect of delays between index manipulation and definitive resection on the incidence of fibrosis is unknown. METHODS: Patients undergoing EMR of previously manipulated colorectal polyps ≥10 mm from 2016 to 2021 at a tertiary referral center were included. Time from index manipulation to definitive resection and the presence of fibrosis were noted. The effects of fibrosis on EMR outcomes were assessed. RESULTS: Among 221 previously manipulated lesions (180 biopsy, 23 incomplete/failed resection, 1 tattoo under lesion, 17 multiple types of manipulation), 51 (23%) demonstrated fibrosis. Fibrotic lesions were found to have been resected significantly later than nonfibrotic lesions (76 vs 61 days; P = .014). In a multivariate analysis controlling for other predictors of fibrosis, each 2-week delay was associated with a 14% increase in the odds of fibrosis. Fibrotic lesions had inferior outcomes with a lower en-bloc resection rate (8% vs 24%; P = .014) and longer procedure time (71 vs 52 minutes; P < .001). Adverse event and recurrence rates were similar between groups. CONCLUSIONS: Delays in definitive resection of previously manipulated polyps are associated with an increased incidence of fibrosis with time and associated inferior outcomes. Manipulation should be discouraged, and if it occurs, prompt referral and scheduling for definitive resection should be prioritized.

Anesthesia Choice and Its Potential Impact on Endoluminal Functional Lumen Imaging Probe Measurements in Esophageal Motility Disorders.

BACKGROUND AND AIMS: The widespread use of peroral endoscopic myotomy (POEM) has revolutionized the management of esophageal motility disorders (EMDs). The introduction of an endoluminal functional lumen imaging probe (EndoFLIP) can serve as a complimentary diagnostic tool to assess the mechanical properties (i.e., pressure, diameter, distensibility and topography) of the esophagus. During EndoFLIP measurements, different anesthesia techniques may induce variable degrees of neuromuscular blockade, potentially affecting esophageal motility and altering the results of EndoFLIP metrics. Our study aimed to compare the impact of using total intravenous anesthesia (TIVA) versus general anesthesia with inhalational anesthetics (GAIA) on diagnostic EndoFLIP measurements. METHODS: We conducted a retrospective study of all adult patients (≥18 years) undergoing EndoFlip during the POEM procedure at our institution between February 2017 and February 2022. We obtained the differences in pressure, diameter, and distensibility index using propofol-based TIVA vs sevoflurane-based GAIA with a 30ml and 60ml balloon. The differences were divided into terciles and compared between diagnoses using univariate comparisons and logistic regression models. RESULTS: 49 patients were included (39% Type 1 achalasia, 43% Type 2 or 3 achalasia, and 18% jackhammer esophagus (JE)). Compared to spastic disorders (Type 2, 3 and JE), Type 1 had lower values of pressure differences at 60 mL in univariate (3.75 vs 15.20 p=0.001) and multivariate (aOR 0.89 95%CI 0.82-0.978) analyses. Compared to Type 1, Type 2 and 3 had higher rates of pressure differences at 60 mL in univariate (9.85 vs 3.75 p=0.04); and nearly reached significance in multivariate analysis (1.09 95%CI 1-1.20). Compared to Type 1, JE demonstrated higher values in pressure differences at 60 mL (27.7 vs 3.75 p<0.001) CONCLUSION: Esophageal pressure, as measured by EndoFLIP, was significantly reduced when patients were sedated with sevoflurane-based GAIA. The use sevoflurane-based GAIA for diagnostic EndoFLIP may potentially lead to the misclassification of spastic disorders as Type I achalasia. Therefore, propofol-based TIVA should be considered over sevoflurane-based GAIA for sedation during the diagnostic test.

Endoscopic Resection Techniques for Duodenal and Ampullary Adenomas.

Background and Aims: Duodenal polyps have a reported incidence of 0.3% to 4.6%. Sporadic, nonampullary duodenal adenomas (SNDAs) comprise less than 10% of all duodenal polyps, and ampullary adenomas are even less common. Nonetheless, the incidence continues to rise because of widespread endoscopy use. Duodenal polyps with villous features or those that are larger than 10 mm may raise concern for malignancy and require removal. We demonstrate endoscopic resection of SNDAs and ampullary adenomas using some of our preferred techniques. Methods: The duodenum has several components that can make EMR of duodenal polyps technically challenging. Not only does the duodenum have a thin muscle layer, but it is also highly mobile and vascular, which may explain higher rates of perforation and bleeding of duodenal EMR reported in the literature compared with colon EMR. A standard adult gastroscope with a distal cap is commonly used for duodenal EMRs. Based on the location, however, side-viewing duodenoscopes or pediatric colonoscopes may be used. To prepare for EMR, a submucosal injection is performed for an adequate lift. The polyp is then resected via stiff monofilament snares and subsequently closed with hemostatic clips if feasible. The ampullectomy technique differs slightly from duodenal EMRs and carries the additional risk of pancreatitis. Submucosal injection in the ampulla may not lift well; thus, its utility is debatable. Biliary sphincterotomy should be performed, and based on endoscopist preference, the pancreatic duct (PD) guidewire can be left during resection to maintain access. After resection, a PD stent is placed to minimize pancreatitis risk. Results: The video shows the aforementioned duodenal EMR techniques. Two clips of ampullectomy are also shown in the video. Conclusions: A few common techniques used to perform duodenal EMR and ampullectomy are highlighted in the video. It is important to understand and manage adverse events associated with these procedures and to have established surveillance plans.

The effect of exercise post vertebral augmentation in osteoporotic patients: A systematic review and meta-analysis.

This meta-analysis investigated the effects of exercise on Visual Analog Scale (VAS) and Oswestry Disability Index (ODI) scores following vertebroplasty or kyphoplasty in osteoporotic fractures. A literature search of PubMed, EMBASE (Elsevier), CiNAHL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Scopus, and Web of Science was conducted from database inception to October 6, 2022. Eligible studies reported osteoporosis patients over 18 years of age with a diagnosis of at least one vertebral fracture via radiography or clinical assessment. This review was registered in PROSPERO (ID: CRD42022340791). Ten studies met the eligibility criteria (n = 889). VAS scores at baseline were 7.75 (95% CI: 7.54, 7.97, I2 = 76.11%). Following initiation of exercise, VAS scores at the endpoint of 12 months were 1.91 (95% CI: 1.53, 2.29, I2 = 92.69%). ODI scores at baseline were 68.66 (95% CI: 56.19, 81.13, I2 = 85%). Following initiation of exercise, ODI scores at the endpoint of 12 months were 21.20 (95% CI: 14.52, 27.87, I2 = 99.30). A two-arm analysis demonstrated improved VAS and ODI for the exercise group compared to non-exercise control at 6 months (MD = -0.70, 95% CI: -1.08, -0.32, I2 = 87% and MD = -6.48, 95% CI: -7.52, -5.44, I2 = 46%, respectively) and 12 months (MD = -0.88, 95% CI: -1.27, -0.49, I2 = 85% and MD = -9.62, 95% CI: -13.24, -5.99, I2 = 93%). Refracture was the only adverse event reported and occurred almost twice as frequently in the non-exercise group than in the exercise group. Exercise rehabilitation post vertebral augmentation is associated with improved pain and functionality, particularly after 6 months of exposure, and may reduce refracture rate.

Integrated Genomic and Clinicopathologic Approach Distinguishes Pancreatic Grade 3 Neuroendocrine Tumor From Neuroendocrine Carcinoma and Identifies a Subset With Molecular Overlap.

Distinguishing grade 3 pancreatic neuroendocrine tumor (G3 PanNET) from neuroendocrine carcinoma (PanNEC) is a known diagnostic challenge, and accurate classification is critical because clinical behavior and therapies differ. Although current recommendations suggest that immunohistochemistry for p53, Rb, ATRX, and DAXX can distinguish most cases, some cases remain difficult to classify using this approach. In this study, we reviewed 47 high-grade neoplasms originally diagnosed as pancreatic neuroendocrine neoplasms. In addition to the currently recommended stains, we performed capture-based sequencing of approximately 500 cancer genes and immunohistochemistry for p16 and trypsin or chymotrypsin. Using an integrated molecular and clinicopathologic approach, 42 (89%) of 47 cases had a clear final diagnosis of either G3 PanNET (n = 17), PanNEC (n = 17), or mixed acinar-NEC (n = 8). The 17 G3 PanNETs demonstrated frequent alterations in MEN1 (71%), DAXX (47%), ATRX (24%), TSC2 (35%), SETD2 (42%), and CDKN2A (41%). Contrary to prior reports, TP53 alterations were also common in G3 PanNETs (35%) but were always mutually exclusive with CDKN2A alterations in this group. The 17 PanNECs demonstrated frequent alterations in TP53 (88%), cell cycle genes RB1 (47%), CCNE1/CCND1 (12%), CDKN2A (29%), and in KRAS (53%) and SMAD4 (41%); TP53 was coaltered with a cell cycle gene in 76% of PanNECs. Diffuse strong p16 staining was observed in 69% of PanNECs in contrast to 0% of G3 PanNETs. The 8 acinar-NECs had recurrent alterations in ATM (25%), APC (25%), and STK11 (25%). Five cases remained difficult to classify, 3 of which exhibited overlapping molecular features with alterations in MEN1 with or without ATRX, and RB1 with or without TP53, making it unclear whether to classify as PanNET or PanNEC. Our data demonstrate that molecular profiling and immunohistochemistry for p16 greatly improve the diagnostic accuracy of high-grade pancreatic neuroendocrine neoplasms and identify a subset of rare cases with overlapping features of both PanNET and PanNEC.

Diagnostic quality model (DQM): an integrated framework for the assessment of diagnostic quality when using AI/ML.

BACKGROUND: Laboratory medicine has reached the era where promises of artificial intelligence and machine learning (AI/ML) seem palpable. Currently, the primary responsibility for risk-benefit assessment in clinical practice resides with the medical director. Unfortunately, there is no tool or concept that enables diagnostic quality assessment for the various potential AI/ML applications. Specifically, we noted that an operational definition of laboratory diagnostic quality - for the specific purpose of assessing AI/ML improvements - is currently missing. METHODS: A session at the 3rd Strategic Conference of the European Federation of Laboratory Medicine in 2022 on "AI in the Laboratory of the Future" prompted an expert roundtable discussion. Here we present a conceptual diagnostic quality framework for the specific purpose of assessing AI/ML implementations. RESULTS: The presented framework is termed diagnostic quality model (DQM) and distinguishes AI/ML improvements at the test, procedure, laboratory, or healthcare ecosystem level. The operational definition illustrates the nested relationship among these levels. The model can help to define relevant objectives for implementation and how levels come together to form coherent diagnostics. The affected levels are referred to as scope and we provide a rubric to quantify AI/ML improvements while complying with existing, mandated regulatory standards. We present 4 relevant clinical scenarios including multi-modal diagnostics and compare the model to existing quality management systems. CONCLUSIONS: A diagnostic quality model is essential to navigate the complexities of clinical AI/ML implementations. The presented diagnostic quality framework can help to specify and communicate the key implications of AI/ML solutions in laboratory diagnostics.

Nontunneling Full Thickness Techniques for Neoplasia.

Colorectal cancer is the third most common cancer worldwide and the fourth leading cause of cancer-related deaths in the world, second in the United States. Although most lesions are managed surgically especially when they have already invaded into the submucosal layer, endoscopic full-thickness resection (EFTR) has become an emerging technique that can serve as a safe and effective alternative management for locally invasive gastrointestinal cancers. This article discusses the indications and various techniques and limitations of nontunneled EFTRs of gastrointestinal cancer and reviews the current literature on the outcomes of EFTR.

Whole genome sequencing reveals the independent clonal origin of multifocal ileal neuroendocrine tumors.

BACKGROUND: Small intestinal neuroendocrine tumors (SI-NETs) are the most common neoplasms of the small bowel. The majority of tumors are located in the distal ileum with a high incidence of multiple synchronous primary tumors. Even though up to 50% of SI-NET patients are diagnosed with multifocal disease, the mechanisms underlying multiple synchronous lesions remain elusive. METHODS: We performed whole genome sequencing of 75 de-identified synchronous primary tumors, 15 metastases, and corresponding normal samples from 13 patients with multifocal ileal NETs to identify recurrent somatic genomic alterations, frequently affected signaling pathways, and shared mutation signatures among multifocal SI-NETs. Additionally, we carried out chromosome mapping of the most recurrent copy-number alterations identified to determine which parental allele had been affected in each tumor and assessed the clonal relationships of the tumors within each patient. RESULTS: Absence of shared somatic variation between the synchronous primary tumors within each patient was observed, indicating that these tumors develop independently. Although recurrent copy-number alterations were identified, additional chromosome mapping revealed that tumors from the same patient can gain or lose different parental alleles. In addition to the previously reported CDKN1B loss-of-function mutations, we observed potential loss-of-function gene alterations in TNRC6B, a candidate tumor suppressor gene in a small subset of ileal NETs. Furthermore, we show that multiple metastases in the same patient can originate from either one or several primary tumors. CONCLUSIONS: Our study demonstrates major genomic diversity among multifocal ileal NETs, highlighting the need to identify and remove all primary tumors, which have the potential to metastasize, and the need for optimized targeted treatments.