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Surgical Pathology Clinics Dec 2023The term nonconventional dysplasia has been coined to describe several underrecognized morphologic patterns of epithelial dysplasia in inflammatory bowel disease (IBD),... (Review)
Review
The term nonconventional dysplasia has been coined to describe several underrecognized morphologic patterns of epithelial dysplasia in inflammatory bowel disease (IBD), but to date, the full recognition of these newly characterized lesions by pathologists is uneven. The identification of nonconventional dysplastic subtypes is becoming increasingly important, as they often present as invisible/flat dysplasia and are more frequently associated with advanced neoplasia than conventional dysplasia on follow-up. This review describes the morphologic, clinicopathologic, and molecular characteristics of seven nonconventional subtypes known to date, as well as their potential significance in the clinical management of IBD patients.
Topics: Humans; Colorectal Neoplasms; Clinical Relevance; Inflammatory Bowel Diseases; Hyperplasia; Carcinoma in Situ
PubMed: 37863560
DOI: 10.1016/j.path.2023.05.006 -
Human Pathology Nov 2023Peutz-Jeghers polyps (PJPs) are hamartomatous polyps that may define patients with Peutz-Jeghers syndrome (PJS), a rare inherited polyposis syndrome with high cancer...
Peutz-Jeghers polyps (PJPs) are hamartomatous polyps that may define patients with Peutz-Jeghers syndrome (PJS), a rare inherited polyposis syndrome with high cancer risk. However, the clinical significance of 1-2 sporadic PJPs (without other PJS stigmata) regarding malignant potential and identification of new PJS probands is still unclear. We identified 112 patients with 524 histologically confirmed PJPs and categorized them based on polyp number into syndromic (n = 38) if ≥3 PJPs or diagnosed PJS, solitary (1 PJP, n = 61), and intermediate (2 PJPs, n = 13). Clinicopathologic features, including presence of dysplasia in the polyp and development of neoplasia in the patient, were compared on a per-patient and per-polyp basis. Whereas patients with solitary and intermediate PJPs were not different from each other, patients with syndromic PJPs were, in multivariate analysis, younger (P = .001) and more likely to develop neoplasia (P = .02) over a 62.6-months median follow-up than patients with sporadic PJPs. On an individual polyp basis, syndromic PJPs were more likely, in multivariate analysis, to occur in the small intestine (P < .001), but less likely to harbor metaplasia (P = .03) or dysplasia (P = .001), than sporadic PJPs. Dysplasia and metaplasia were more likely in larger PJPs, by multivariate analysis (P = .007 and P < .001, respectively). These data suggest that strict criteria for PJS (including ≥3 PJPs), as currently used, stratify patients into distinct groups with significant differences in clinicopathologic parameters, particularly regarding risk of neoplasia. However, sporadic PJPs exhibit characteristics such as dysplasia and are thus important to recognize and diagnose but perhaps as heralding only a forme fruste PJS.
Topics: Humans; Polyps; Intestinal Polyps; Peutz-Jeghers Syndrome; Hamartoma; Hyperplasia; Metaplasia
PubMed: 37776958
DOI: 10.1016/j.humpath.2023.09.008 -
Bone Sep 2023Increased RANKL expression is observed in the bone tissue of fibrous dysplasia of bone/McCune-Albright syndrome (FD/MAS). In one animal model of FD/MAS, the inhibition... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Increased RANKL expression is observed in the bone tissue of fibrous dysplasia of bone/McCune-Albright syndrome (FD/MAS). In one animal model of FD/MAS, the inhibition of RANKL reduced tumor volume. A beneficial effect of denosumab on pain in patients refractory to bisphosphonates has been reported, but without systematic quantification of pain improvement. This work describes the clinical experience of our group on the efficacy on pain of denosumab treatment, along with safety, in FD/MAS patients refractory to bisphosphonates.
MATERIALS AND METHODS
We have conducted a retrospective multicenter study in 6 academic rheumatology centers in France. We have collected patients and FD/MAS characteristics, duration of prior exposure to bisphosphonates, denosumab treatment modalities (dosage - administration regimen - number of courses); evolution of pain evaluated by Visual Analogic Scale (VAS).
RESULTS
13 patients were included (10 women and 3 men) 45 years on average, 5 MAS, 4 monostotic and 4 polyostotic forms. The average duration post-diagnosis of FD/MAS was 25 years and the mean duration of prior exposure to bisphosphonates was 4.7 years. Pain could be analyzed in 7 patients, showing a significant improvement from a mean VAS of 7.8 to 2.9 (-4.9 points, p = 0.003). In one patient with fronto-orbital FD/MAS, a 30 % decrease in lesional volume, assessed by MRI, was observed within 6 months of treatment, that was sustained over the following 12 months. Treatment regimens were heterogeneous. No hypercalcemia was observed after treatment cessation and the clinical tolerance was good.
DISCUSSION
This study suggests that denosumab reduces pain in patients with DF/MAS refractory to bisphosphonates, and quantifies this improvement for the first time in a multicenter study. In our cohort, no patients who discontinued denosumab developed hypercalcemia and clinical tolerance was overall good. This study also provides encouraging data regarding lesion volume control. Further controlled studies are required to determine the place and modalities of the denosumab treatment of FD/MAS.
CONCLUSION
Denosumab significantly decreased pain in FD/MAS refractory to bisphosphonate. This study paves the way for a randomized clinical trial to validate and standardize the prescription of denosumab in FD/MAS.
Topics: Animals; Female; Diphosphonates; Denosumab; Retrospective Studies; Fibrous Dysplasia of Bone; Fibrous Dysplasia, Polyostotic; Pain
PubMed: 37301527
DOI: 10.1016/j.bone.2023.116819 -
Clinics in Perinatology Mar 2024Preterm infants with bronchopulmonary dysplasia (BPD) are prone to develop pulmonary hypertension (PH). Strong laboratory and clinical data suggest that antenatal... (Review)
Review
Preterm infants with bronchopulmonary dysplasia (BPD) are prone to develop pulmonary hypertension (PH). Strong laboratory and clinical data suggest that antenatal factors, such as preeclampsia, chorioamnionitis, oligohydramnios, and placental dysfunction leading to fetal growth restriction, increase susceptibility for BPD-PH after premature birth. Echocardiogram metrics and serial assessments of NT-proBNP provide useful tools to diagnose and monitor clinical course during the management of BPD-PH, as well as monitoring for such complicating conditions as left ventricular diastolic dysfunction, shunt lesions, and pulmonary vein stenosis. Therapeutic strategies should include careful assessment and management of underlying airways and lung disease, cardiac performance, and systemic hemodynamics, prior to initiation of PH-targeted drug therapies.
Topics: Infant; Infant, Newborn; Female; Humans; Pregnancy; Bronchopulmonary Dysplasia; Hypertension, Pulmonary; Infant, Premature; Placenta; Premature Birth
PubMed: 38325941
DOI: 10.1016/j.clp.2023.12.002 -
EClinicalMedicine Sep 2023Endoscopy surveillance is recommended for mild-moderate dysplasia and negative endoscopy findings every 3 years and 5 years, respectively, but evidence is limited. This...
BACKGROUND
Endoscopy surveillance is recommended for mild-moderate dysplasia and negative endoscopy findings every 3 years and 5 years, respectively, but evidence is limited. This study aimed to assess long-term esophageal cancer (EC) incidence and mortality after a single endoscopy screening.
METHODS
We included individuals at high risk of EC aged 40-69 years who underwent endoscopy screening in 2007-2012 at six centres in rural China and had a baseline diagnosis of negative endoscopy findings, mild dysplasia, or moderate dysplasia. Participants were followed up for EC incidence and mortality. Cumulative incidence and mortality rates of EC were estimated by Kaplan-Meier analyses. Cox regression models were used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between baseline endoscopy diagnosis and the risk of EC incidence and mortality. EC incidence and mortality after a single endoscopy screening were compared with those of the population in rural China by the standardized incidence ratio (SIR) and standardized mortality ratio (SMR).
FINDINGS
A total of 42,827 participants (40,977 with negative endoscopy findings, 1562 with mild dysplasia, and 288 with moderate dysplasia) were included; 268 EC cases and 128 EC deaths were identified during a median follow-up of 10.62 years. The cumulative EC incidence at 10 years was 0.45% (0.38-0.52) in the group with negative endoscopy findings, 2.39% (1.62-3.16) in the mild dysplasia group, and 8.90% (5.57-12.24) in the moderate dysplasia group, and the cumulative EC mortality at 10 years was 0.23% (0.18-0.27), 0.96% (0.46-1.46), and 2.50% (0.67-4.33), respectively. Compared with individuals with negative endoscopy findings, the HRs for EC incidence and mortality in the mild dysplasia group were 3.52 (2.49-4.97) and 2.43 (1.41-4.19), and those in the moderate dysplasia group were 13.18 (8.78-19.76) and 6.46 (3.13-13.29), respectively. The SIR was 0.53 (0.40-0.70) for the group with negative endoscopy findings, 1.95 (1.69-2.24) for the mild dysplasia group, and 6.75 (6.25-7.28) for the moderate dysplasia group, with the SMRs of 0.43 (0.31-0.58), 1.07 (0.88-1.29) and 2.67 (2.36-3.01), respectively.
INTERPRETATION
Individuals with negative endoscopy findings after a single endoscopy screening had a lower EC risk than the general population for up to 10.62 years, while those with mild-moderate dysplasia had an elevated risk. Our results support endoscopy surveillance for mild-moderate dysplasia every 3 years and suggest extending the interval to 10 years after a negative endoscopy finding.
FUNDING
National Key R&D Programme of China, Special Project of Beijing-Tianjin-Hebei Basic Research Cooperation, and Sanming Project of Medicine in Shenzhen.
PubMed: 37680952
DOI: 10.1016/j.eclinm.2023.102201 -
Human Pathology Jan 2024Gastric metaplasia in colonic mucosa with inflammatory bowel disease (IBD) develops as an adaptation mechanism. The association between gastric metaplasia and...
Gastric metaplasia in colonic mucosa with inflammatory bowel disease (IBD) develops as an adaptation mechanism. The association between gastric metaplasia and nonconventional and/or conventional dysplasia as precursors of colitis-associated colorectal cancer is unknown. To address this question, we retrospectively reviewed a series of 33 IBD colectomies to identify gastric metaplasia in 76 precursor lesions. We obtained 61 nonconventional and 15 conventional dysplasias. Among nonconventional dysplasia, 31 (50.8 %) were low-grade (LGD), 4 (6.5 %) were high-grade (HGD), 9 (14.8 %) had both LGD and HGD, and 17 (27.9 %) had no dysplasia (ND), while 14 (93 %) conventional dysplasias had LGD, and 1 (7 %) had LGD and HGD. Gastric metaplasia was assessed by concomitant immunoexpression of MUC5AC and loss of CDX2 staining. Expression of a p53-mut pattern was considered as a surrogate for gene mutation, and complete loss of MLH1 staining as presence of MLH1 hypermethylation. In nonconventional dysplasia, MUC5AC immunoexpression decreased as the degree of dysplasia increased, being 78 % in LGD and 39 % in HGD (p = 0.006). CDX2 was lost in epithelial glands with high expression of MUC5AC (p < 0.001). The p53-mut pattern was observed in 77 % HGD, 45 % LGD, and in 6 % with ND (p < 0.001). Neither nonconventional nor conventional dysplasia showed complete loss of MLH1 staining. Gastric metaplasia was also present in mucosa adjacent to nonconventional dysplasia with chronic changes or active inflammation. Our results show that gastric metaplasia appears in IBD-inflamed colon mucosa, it is the substrate of most nonconventional dysplasia and occurs prior to p53 alterations.
Topics: Humans; Retrospective Studies; Tumor Suppressor Protein p53; Inflammatory Bowel Diseases; Colon; Hyperplasia; Metaplasia; Precancerous Conditions
PubMed: 38000679
DOI: 10.1016/j.humpath.2023.11.011 -
Neurobiology of Disease Oct 2023De novo somatic (post-zygotic) gene mutations affecting neuroglial progenitor cell types in embryonic cerebral cortex are increasingly identified in patients with drug... (Review)
Review
De novo somatic (post-zygotic) gene mutations affecting neuroglial progenitor cell types in embryonic cerebral cortex are increasingly identified in patients with drug resistant epilepsy (DRE) associated with malformations of cortical development, in particular, focal cortical dysplasias (FCD). Somatic variants in at least 16 genes have been linked to FCD type II, all encoding components of the mechanistic target of rapamycin (mTOR) pathway. FCD type II is characterized histopathologically by cytomegalic dysmorphic neurons and balloon cells. In contrast, the molecular pathogenesis of FCD I subtypes is less well understood, and histological features are characterized by alterations in columnar or laminar organization without cytomegalic dysmorphic neurons or balloon cells. In 2018, we reported somatic mutations in Solute Carrier Family 35 member A2 (SLC35A2) linked to DRE underlying FCD type I and subsequently to a new histopathological phenotype: excess oligodendrocytes and heterotopic neurons in subcortical white matter known as MOGHE (mild malformation of cortical development with oligodendroglial hyperplasia). These discoveries opened the door to studies linking somatic mutations to FCD. In this review, we discuss the biology of SLC35A2 somatic mutations in epilepsy in FCD and MOGHE, and insights into SLC35A2 epilepsy pathogenesis, describing progress to date and critical areas for investigation.
Topics: Humans; Drug Resistant Epilepsy; Focal Cortical Dysplasia; Epilepsy; Malformations of Cortical Development, Group I; Malformations of Cortical Development
PubMed: 37739137
DOI: 10.1016/j.nbd.2023.106299 -
Orthopaedic Journal of Sports Medicine Oct 2023Developmental dysplasia of the hip (DDH) and trochlear dysplasia (TD) are distinct pathologies with several important features in common. In addition to shared risk...
BACKGROUND
Developmental dysplasia of the hip (DDH) and trochlear dysplasia (TD) are distinct pathologies with several important features in common. In addition to shared risk factors, both forms of dysplasia cause abnormal joint kinematics and force transmission, predisposing patients to pain, injuries to cartilage and soft tissue stabilizers, and ultimately arthritis.
PURPOSE
To evaluate for an association between hip dysplasia and TD in skeletally mature patients with symptomatic hip dysplasia.
STUDY DESIGN
Cross-sectional study; Level of evidence, 3.
METHODS
A total of 48 patients with DDH who underwent periacetabular osteotomy were compared with 48 sex-matched patients who underwent hip arthroscopy for femoroacetabular impingement (FAI) between July 2014 and February 2021. All patients were skeletally mature. The Tönnis angle and lateral center-edge angle were measured on preoperative pelvis radiographs. Femoral version, trochlear depth, lateral trochlear inclination (LTI), tibial tubercle-trochlear groove distance (TTTG-d), and posterior lateral condylar angle (PLCA) were measured on preoperative magnetic resonance imaging scans of the symptomatic hip and ipsilateral knee. Continuous variables were compared between the patient groups using 2-sample tests. Interobserver reliability was measured using the intraclass correlation coefficient.
RESULTS
Patients with DDH demonstrated a reduced trochlear depth compared with patients with FAI (3.6 vs 4.6 mm; < .001). There were no differences between groups in femoral anteversion, LTI, TTTG-d, or PLCA. Two (4.2%) patients with FAI and 17 (35.4%) patients with DDH had a trochlear depth <3 mm ( < .001). One (2.1%) patient with FAI and 7 (14.6%) patients with DDH had an LTI <11° ( = .027). There was no difference between groups in frequency of a convex proximal trochlea, patient-reported ipsilateral knee pain, or ipsilateral knee procedures.
CONCLUSION
Patients with DDH had reduced trochlear depth compared with patients with FAI, demonstrating a higher incidence of dysplastic trochlear features that may predispose patients to patellofemoral joint disease. Further research is needed to determine whether screening at-risk patients and treating TD will help to prevent symptomatic patellofemoral disease.
PubMed: 37822419
DOI: 10.1177/23259671231200805 -
BMC Surgery Aug 2023The aim of this study was to compare the clinical characteristics of ulcerative colitis (UC) patients who underwent surgery for cancer/dysplasia with those who underwent...
PURPOSE
The aim of this study was to compare the clinical characteristics of ulcerative colitis (UC) patients who underwent surgery for cancer/dysplasia with those who underwent surgery for refractory disease and to discuss the preoperative preparation for successful hand-sewn IPAA.
METHODS
Patients who underwent surgery for UC between January 2014 and December 2021 at Hyogo Medical University were included in the study. A total of 443 UC surgical cases were included in the study, which comprised 188 cancer/dysplasia patients and 255 refractory patients. Clinical records were compared retrospectively.
RESULTS
The proportion of surgical UC cases with cancer/dysplasia has been on the rise, accounting for approximately 40% in recent years. The duration of disease (months) was 186 (2-590) in the cancer/dysplasia group and 48 (1-580) in the refractory group (p = 0.02). UC severity (mild/moderate/severe) was 119/69/0 in the cancer/dysplasia group and 18/157/80 in the refractory group (p < 0.01). The four nutrition factors of weight (55.2 (32.7-99.6) kg: 49.9 (20.3-85.2) kg), body mass index (21.0 (13.9-32.5) kg/m2: 18.3 (11.4-34.1)kg/m2), serum albumin level (4.3 (2.7-5.0)g/dl: 3.4 (1.4-5.2)g/dl) and prognostic nutrition index (49.2 (33.2-61.2): 40.9 (17.4-61.1)) were significantly higher in the cancer/dysplasia group (p < 0.01). The degree of obesity was also significantly higher in the cancer/dysplasia group (p < 0.01).
CONCLUSION
UC patients with cancer/dysplasia were more likely than refractory patients to have mild inflammation; they also had a longer duration of UC disease and better nutritional status.
Topics: Humans; Colitis-Associated Neoplasms; Colitis, Ulcerative; Retrospective Studies; Hyperplasia; Body Mass Index
PubMed: 37641118
DOI: 10.1186/s12893-023-02160-x -
Clinical Medicine Insights. Arthritis... 2023Hip osteoarthritis (HOA) is a growing burden and one of the leading causes of hip pain. The relationship between the HOA and the alignment of the spinopelvic region has...
BACKGROUND
Hip osteoarthritis (HOA) is a growing burden and one of the leading causes of hip pain. The relationship between the HOA and the alignment of the spinopelvic region has been intensively studied, however the issue remains controversial. Spinopelvic imbalance, HOA, and dysplasia were investigated in relation to sagittal spinopelvic parameters in this study.
METHODS
We collected computerized tomography (CT) topograms of the pelvis or abdomen from 380 patients. In antero-posterior (AP) topograms, Tonnis grading, center-edge angle (CEA) and Sharp's acetabular angle (AA) measurements were performed on each patient. Lateral topograms were used to evaluate the following spinopelvic parameters for each patient: pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), sacral table angle (STA), lumbar lordosis (LL), proximal lumbar lordosis (PLL), distal lumbar lordosis (DLL), and PI-LL difference. Initially, the cohort was divided into two subgroups based on whether or not they had HOA. Then, they were divided into two subgroups based on whether or not they had dysplasia. Ultimately, it was divided in half based on the PI-LL imbalance. Statistical analyses were conducted to determine the likely correlations between the spinopelvic parameters of these subgroups. In addition, the correlations between spinopelvic parameters were investigated.
RESULTS
There were 380 patients evaluated. We found no association between HOA or dysplasia and spinopelvic parameters. In addition, there was no association between PI-LL imbalance and HOA or dysplasia.
CONCLUSION
There was no difference in constant PI and STA angle, besides other variable parameters, between groups having HOA and dysplasia or not. PI-LL imbalance has no effect on HOA and dysplasia.
PubMed: 37701625
DOI: 10.1177/11795441231191790