Ductal Morphology Research Articles

Oral N-acetylcysteine ameliorates liver fibrosis and enhances regenerative responses in Mdr2 knockout mice

Cholangiopathies are poorly understood disorders with no effective therapy. The extrahepatic biliary tree phenotype is less studied compared to the intrahepatic biliary injury in both human disease and Mdr2−/− mice, the established cholestatic mouse model. This study aimed to characterize the extra hepatic biliary tree of Mdr2−/− mice at various ages and to determine if injury can be repaired with the antioxidant and glutathione precursor N-acetyl-L-Cysteine treatment (NAC). We characterized extra hepatic bile ducts (EHBD)s at various ages from 2 to 40 weeks old FVB/N and Mdr2−/− mice. We examined the therapeutic potential of local NAC ex vivo using EHBD explants at early and late stages of injury; and systematic therapy by in vivo oral administration for 3 weeks. EHBD and liver sections were assessed by histology and immunofluorescent stains. Serum liver enzyme activities were analyzed, and liver spatial protein expression analysis was performed. Mdr2−/− mice developed progressive EHBD injury, similar to extrahepatic PSC. NAC treatment of ex vivo EHBD explants led to improved duct morphology. In vivo, oral administration of NAC improved liver fibrosis, and decreased liver enzyme activities. Spatial protein analysis revealed cell-type specific differential response to NAC, collectively indicating a transition from pro-apoptotic into proliferative state. NAC treatment should be further investigated as a potential therapeutic option for human cholangiopathies.

Abstract C079: Exploring acinar to ductal metaplasia in pancreatitis and precancerous contexts using FixNCut

Abstract Acinar to ductal metaplasia (ADM) is the process by which acinar cells transition to a duct-like state acquiring ductal markers and morphology. This process can be driven by pancreas inflammation or injury, such as pancreatitis, where it is thought to be an adaptive response to help mitigate damage and facilitate repair. ADM is also observed following acinar-specific oncogenic KRAS mutations and known to precede PDAC precancerous lesions termed pancreatic intraepithelial neoplasias (PanINs). While ADM is well characterized histologically, cellular and molecular details of ADM and PanIN formation remain less well understood, in part due to high levels of digestive enzyme production in acinar cells that hamper characterization. Leveraging our recently described DSP-fixation method, FixNCut, to improve capture and transcriptome quality of acinar and ADM populations in the pancreas, we characterize ADM arising in three contexts: acute pancreatitis, recurrent acute pancreatitis, and acute pancreatitis with an oncogenic KRAS mutation known to drive the formation of PanINs. FixNCut and single-cell RNA-sequencing enabled us to elucidate the transcriptomic landscape of ADM and define changes to the microenvironment in unprecedented detail. Our findings indicate that the cellular and transcriptional landscape of recurrent acute pancreatitis closely mirrors that of acute pancreatitis for up to 6 weeks (or 6 bouts of 2-day acute pancreatitis), which was the longest timepoint tested. In contrast, acute pancreatitis in the presence of an acinar-specific oncogenic KRAS mutation results in a distinct transcriptional profile for both ADM and the surrounding microenvironment compared to pancreatitis alone. Additionally, we use FixNCut to preserve the epigenomes of acinar cells, enabling us to sort acinar cells and profile their histone modifications in various contexts of ADM. We benchmark and validate our results against existing mouse and human datasets of precancer and cancer. Through this work, we aim to enhance our understanding of ADM in various contexts, providing insights into acinar cell plasticity and early PDAC precursor formation that may inform strategies for early detection and interception. Citation Format: Katherine Aney, Woo-Jeong Jeong, Pal Koak, Isabel Kim, Sahar Nissim. Exploring acinar to ductal metaplasia in pancreatitis and precancerous contexts using FixNCut [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr C079.

The mammary hair of Monodelphis domestica and homology of the mammary pilosebacous unit.

The unitary mammary gland is a synapomorphy of therian mammals and is thought to have evolved from the pilosebaceous organ in the mammalian stem lineage from which the lactogenic patch of monotremes is also derived. One of the key lines of evidence for the homology of the nipple and the lactogenic patch is that marsupials have retained a transient hair associated with developing mammary glands. However, these structures have not been documented since the early 20th-century drawings of Ernst Bresslau. In this study, we examine the developing mammary organs of Monodelphis domestica and document the presence of mammary hairs in 12-week-old females, as well as their absence after 18 weeks of age. Histochemical staining for cystine confirms the structures as keratinized hairs. Milk ducts of both juvenile and adult nipples show a division between KRT18+ luminal epithelium and KRT14+ ACTA2+ myoepithelium. These patterns match those in eutherians and suggest a conserved ductal morphology and mechanism of milk expulsion. Finally, PTHLH, a peptide hormone which promotes homeotic transformation of hairy skin into hairless nipples in the mouse, was detected in the Monodelphis milk duct during the mammary hair stage, suggesting that the mutual exclusivity of "hairless nipple" and "hair" organ identity is derived in eutherian mammals. These results reveal shared characteristics of the M. domestica nipple with both the eutherian nipple and the pilosebaceous organ, consistent with the evolutionary derivation of the mammary gland from an ancestral hair organ via developmental individualization of pilosebaceous and mammary identities.

Macroscopic and Histological Effects of Polycaprolactone Dermal Filler in the Orofacial Region: A Study in Rats

The objective of our study was to evaluate early and late macroscopic and histological changes associated with the use of polycaprolactone dermal filler (PCL) in the orofacial region. Forty-eight female Wistar rats were divided into the PCL group and the control group. The material was applied to the ventral tongue and submandibular region, and the animals were euthanized at three time points—24 h, and 30 and 90 days. In the PCL group, yellowish nodules were observed on the tongue at all experimental time points. At the 24 h mark, the histological analysis revealed the presence of the PCL and a predominance of lymphocytes, plasma cells, and neutrophils. At 30 and 90 days, macrophages and multinucleated giant cells predominated around the PCL spheres. Collagen density in the dermis was higher in the PCL group when compared to the control at 30 and 90 days. In the submandibular glands, an inflammatory process similar to that observed at other sites was noted, with no alterations in acinar or ductal morphology. The results of this study highlight the effectiveness of PCL as a collagen biostimulator. Nevertheless, the development of nodular lesions on the tongue signals the potential risk of complications in mobile anatomical structures.

Spatial molecular profiling of mixed invasive ductal and lobular breast cancers reveals heterogeneity in intrinsic molecular subtypes, oncogenic signatures, and mutations

Mixed invasive ductal and lobular carcinoma (MDLC) is a rare histologic subtype of breast cancer displaying both E-cadherin positive ductal and E-cadherin negative lobular morphologies within the same tumor, posing challenges with regard to anticipated clinical management. It remains unclear whether these distinct morphologies also have distinct biology and risk of recurrence. Our spatially resolved transcriptomic, genomic, and single-cell profiling revealed clinically significant differences between ductal and lobular tumor regions including distinct intrinsic subtype heterogeneity - e.g., MDLC with triple-negative breast cancer (TNBC) or basal ductal and estrogen receptor positive (ER+) luminal lobular regions, distinct enrichment of cell cycle arrest/senescence and oncogenic (ER and MYC) signatures, genetic and epigenetic CDH1 inactivation in lobular but not ductal regions, and single-cell ductal and lobular subpopulations with unique oncogenic signatures further highlighting intraregional heterogeneity. Altogether, we demonstrated that the intratumoral morphological/histological heterogeneity within MDLC is underpinned by intrinsic subtype and oncogenic heterogeneity which may result in prognostic uncertainty and therapeutic dilemma.

Who Still Gets Ligated? Reasons for Persistence of Surgical Ligation of the Patent Ductus Arteriosus Following Availability of Transcatheter Device Occlusion for Premature Neonates.

(1) Background: To identify reasons for the persistence of surgical ligation of the patent ductus arteriosus (PDA) in premature infants after the 2019 Food and Drug Administration (FDA) approval of transcatheter device closure; (2) Methods: We performed a 10-year (2014-2023) single-institution retrospective study of premature infants (<37 weeks) and compared clinical characteristics and neonatal morbidities between neonates that underwent surgical ligation before (epoch 1) and after (epoch 2) FDA approval of transcatheter closure; (3) Results: We identified 120 premature infants that underwent surgical ligation (n = 94 before, n = 26 after FDA approval). Unfavorable PDA morphology, active infection, and recent abdominal pathology were the most common reasons for surgical ligation over device occlusion in epoch 2. There were no differences in demographics, age at closure, or outcomes between infants who received surgical ligation in the two epochs; (4) Conclusions: Despite increasing trends for transcatheter PDA closure in premature infants, surgical ligation persists due to unfavorable ductal morphology, active infection, or abdominal pathology.

Novel 3D morphological characteristics for congenital biliary dilatation diagnosis: a case-control study.

Congenital biliary dilatation (CBD) necessitates the timely removal of dilated bile ducts. Accurate differentiation between CBD and secondary biliary dilatation (SBD) is crucial for treatment decisions, and identification of CBD with intrahepatic involvement is vital for surgical planning and supportive care. This study aimed to develop quantitative models based on bile duct morphology to distinguish CBD from SBD and further identify CBD with intrahepatic involvement. The retrospective study included 131 CBD and 209 SBD patients between December 2014 and December 2021 for model development, internal validation, and testing. A separate cohort of 15 CBD and 34 SBD patients between January 2022 and December 2022 was recruited for temporally-independent validation. Quantitative shape-based (Shape) and diameter-based (Diam) morphological characteristics of bile ducts were extracted to build a CBD diagnosis model to distinguish CBD from SBD and an intrahepatic involvement identification model to classify CBD with/without intrahepatic involvement. The diagnostic performance of the models was compared with that of experienced hepatobiliary surgeons. The CBD diagnosis model using clinical, Shape, and Diam characteristics showed good performance with an AUROC of 0.942 (95% CI: 0.890-0.994), AUPRC of 0.917 (0.855-0.979), accuracy of 0.891, sensitivity of 0.950, and F1-score of 0.864. The model outperformed two experienced surgeons in accuracy, sensitivity, and F1-score. The intrahepatic involvement identification model using clinical, Shape, and Diam characteristics yielded outstanding performance with an AUROC of 0.944 (0.879-1.000), AUPRC of 0.982 (0.947-1.000), accuracy of 0.932, sensitivity of 0.971, and F1-score of 0.957. The models demonstrated generalizable performance on the temporally-independent validation cohort. This study developed two robust quantitative models for distinguishing CBD from SBD and identifying CBD with intrahepatic involvement, respectively, based on morphological characteristics of the bile ducts, showing great potential in risk stratification and surgical planning of CBD.

Population factors predicting survival in breast cancer: analysis according to the data of the Arkhangelsk Regional Cancer Registry in 2000–2020

Background. Breast cancer (BC) is the leading cancer in the world and in Russia. Epidemiological factors predicting breast cancer survival in Russia have not been studied enough. Aim. To evaluate the factors predicting survival in BC by the data of the Arkhangelsk Regional Cancer Registry in 2000–2020 and the survival during the COVID-19 pandemic Materials and methods. Data on all cases of Вс for 2000–2020 retrieved from the Arkhangelsk Regional Cancer Registry database. Cancer-specific survival was estimated using the Kaplan–Meier and the life tables method. The prognostic value of variables available in Arkhangelsk Regional Cancer Registry was assessed in Cox regression. Results. The final analysis included 9,089 cases of breast cancer. During the observation period, 2723 deaths from breast cancer were registered. The one-, five- and ten-year survival rates in the entire population were 91.6 %, 73.0 % and 64.0 %, respectively. In a multivariate analysis, the risk of death from BC increased by 2.9, 8.2, 21.3 and 6.8 at 2, 3, 4 and unknown stages; 2.1 times with the localization of the tumor in the area of the nipple and areola; by 33 % in ductal cancer compared with lobular cancer, by 1.8 and 2.6 times in those who received palliative treatment and did not receive treatment; by 33 % in women aged 80 years and older; by 22 % for those living in rural areas. In the period 2013–2019, the 5-year cancer-specific survival reached 79.1 %, which is 14 % and 6 % higher than in the periods 2000–2006 and 2007–2012. Survival rates have not declined during the COVID-19 pandemic. Conclusion. The risk of death from BC is increased in advanced stages, ductal morphology, localization in the nipple-areolar region, age over 80 years, and living in rural areas. During the COVID-19 pandemic BC survival did not worsen, but this requires further study.

Targeting Cellular Senescence in Organ Transplantation.

Targeting Cellular Senescence in Organ Transplantation.

Increased whitebark pine (Pinus albicaulis) growth and defense under a warmer and regionally drier climate

IntroductionTree defense characteristics play a crucial role in modulating conifer bark beetle interactions, and there is a growing body of literature investigating factors mediating tree growth and resin-based defenses in conifers. A subset of studies have looked at relationships between tree growth, resin duct morphology and climate; however, these studies are almost exclusively from lower-elevation, moisture-limited systems. The relationship between resin ducts and climate in higher-elevation, energy-limited ecosystems is currently poorly understood.MethodsIn this study, we: (1) evaluated the relationship between biological trends in tree growth, resin duct anatomy, and climatic variability and (2) determined if tree growth and resin duct morphology of whitebark pine, a high-elevation conifer of management concern, is constrained by climate and/or regional drought conditions.ResultsWe found that high-elevation whitebark pine trees growing in an energy-limited system experienced increased growth and defense under warmer and regionally drier conditions, with climate variables explaining a substantive proportion of variation (∼20–31%) in tree diameter growth and resin duct anatomy.DiscussionOur results suggest that whitebark pine growth and defense was historically limited by short growing seasons in high-elevation environments; however, this relationship may change in the future with prolonged warming conditions.

Abstract P6-04-12: Differential diagnoses of breast biopsies by spatial parametric modeling of histological structures and explainable AI

Abstract Background: Pathologists typically diagnose the breast tissue slides under a microscope by examining: (i) lumen and ductal morphology, (ii) nuclei size, shape, and spatial arrangement and their combinations, (iii) intraductal architecture, and (iv) textural properties. These features may be subtle and can overlap between diagnoses which contribute to inter- and intra-observer variability. We aim to mitigate this arbitrary nature of breast diagnoses with an exemplar-driven precision pathology pipeline based on spatial parametric modeling of histological structures. Methods: For our study, we consider a broad spectrum of breast biopsies including: (i) invasive breast cancer, (ii) three high-risk benign lesions: ductal carcinoma in-situ, atypical ductal hyperplasia (ADH), flat epithelial atypia (FEA), and (iii) three low-risk benign lesions: usual ductal hyperplasia, columnar cell change and Normal; where the risk is indicated by the relative chance of developing breast cancer. We build spatial parametric models for a dictionary of histological structures that pathologists frequently use (also documented in the standard reference book from WHO on the classification of tumors) in making complex diagnostic decisions. These models enable our precision pathology pipeline to simultaneously identify distinct exemplar images to account for inter-class heterogeneity, and learn the relative importance of lumen/ductal morphology (LD), intraductal structures including nuclei morphology and spatial arrangements (ID) and textural features (T) from automatically identified exemplar images in assigning diagnostic labels. In doing so, we assert that the assignment of relative importances to LD, ID, and T features is driven by similar looking ducts (‘exemplars’) which were previously encountered during pathology training or clinical practice. Results: We evaluated the inferential power of our exemplar-driven precision pathology pipeline on two separate breast core biopsy image datasets, i) dataset containing 4539 regions of interest (ROIs) images extracted from 387 whole slide images (WSIs, 40x), and ii) dataset containing 1237 ROI images extracted from 93 WSIs (20x). Our precision pathology pipeline shows significant improvement (~20%) in the overall classification performance compared to state-of-the-art black box deep learning methods (e.g., graphical neural networks) on both datasets. In particular, while our performance in detecting invasive lesions is comparable to baseline methods, we show a significant improvement (p&amp;lt; 0.01) in detecting diagnostically important high-risk ADH and FEA ROIs compared to the baseline methods, where inter- and intra-observer variability is a problem. Conclusions: A key highlight of our method is in its ability to provide pathologist friendly diagnostic explanations without largely compromising on the classification performance. The strategy outlined in this work can be generalized to other tissue histologies from other organs as defined in the WHO Classification of Tumors books. Further, our approach can facilitate a communication platform between pathologists and computational scientists to interact and develop AI-driven algorithmic tools that can enhance patient care in a clinical setting. Our framework provides pathologist-friendly explanations paving the way for better, transparent, and trustworthy diagnostic tools. Differential diagnoses of breast biopsies Differential diagnoses of breast biopsies The precision pathology pipeline optimizes the identification of a broad spectrum of breast biopsies (invasive, DCIS, benign), including difficult borderline cases (e.g., ADH, FEA, etc.). It provides pathologist-friendly explanations integrated into a clinical workflow for better, transparent, and trustworthy diagnostic aid. This approach sddresses the limitations of standard black-box AI in building trust with pathologists. Citation Format: Akif Burak Tosun, S. Chakra Chennubhotla. Differential diagnoses of breast biopsies by spatial parametric modeling of histological structures and explainable AI [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-04-12.

Gldc Is Essential for Renal Progenitor Patterning during Kidney Development.

The glycine cleavage system (GCS) is a complex located on the mitochondrial membrane that is responsible for regulating glycine levels and contributing one-carbon units to folate metabolism. Congenital mutations in GCS components, such as glycine decarboxylase (gldc), cause an elevation in glycine levels and the rare disease, nonketotic hyperglycinemia (NKH). NKH patients suffer from pleiotropic symptoms including seizures, lethargy, mental retardation, and early death. Therefore, it is imperative to fully elucidate the pathological effects of gldc dysfunction and glycine accumulation during development. Here, we describe a zebrafish model of gldc deficiency that recapitulates phenotypes seen in humans and mice. gldc deficient embryos displayed impaired fluid homeostasis suggesting renal abnormalities, as well as aberrant craniofacial morphology and neural development defects. Whole mount in situ hybridization (WISH) revealed that gldc transcripts were highly expressed in the embryonic kidney, as seen in mouse and human repository data, and that formation of several nephron segments was disrupted in gldc deficient embryos, including proximal and distal tubule populations. These kidney defects were caused by alterations in renal progenitor populations, revealing that the proper function of Gldc is essential for the patterning of this organ. Additionally, further analysis of the urogenital tract revealed altered collecting duct and cloaca morphology in gldc deficient embryos. Finally, to gain insight into the molecular mechanisms underlying these disruptions, we examined the effects of exogenous glycine treatment and observed analogous renal and cloacal defects. Taken together, these studies indicate for the first time that gldc function serves an essential role in regulating renal progenitor development by modulating glycine levels.

Extraction of plant parenchyma by computer image processing technology

People are increasingly using different kinds of plant products, such as wood, but there are many kinds of wood and it is difficult to analyze and identify them, so how to use auxiliary equipment to analyze wood and achieve the goal of accurate wood identification without damaging the product itself has become one of the important problems to be solved in the field of wood research. The axial thin-walled tissue has important wood grain information and it is one of the important features for wood identification. In this paper, we studied the microscopic images of broadleaf wood, and obtained the microstructure images of wood cross-section by photographing, and extracted the complete axial thin-walled tissue morphology of wood by using computer image processing technology and other ways about computer vision. Firstly, the axial thin-walled wood images were de-noised to eliminate some noise effects, so as to facilitate the separation of the axial thin-walled wood; then the images were processed by mathematical morphology to successfully extract the axial thin-walled wood and duct morphology from the cross-sectional images of broadleaf wood; finally, the axial thin-walled wood was separated from the duct by calculating the area of the closed area.

A Better Way for Ductal Stenting in Patients with Duct-Dependent Pulmonary Flow and Vertical and Tortuous Patent Ductus Arteriosus.

In this study, we aimed to compare the femoral route and the carotid artery route in terms of procedural success of ductal stent implantation in patients with ductdependent pulmonary blood flow. The study included 51 patients with duct-dependent pulmonary circulation who underwent ductal stent implantation upon their admission to our clinic between July 2017 and March 2021. In total, 23 patients (group I) underwent ductal stent implantation via the femoral route, while the remaining 28 (group II) underwent the procedure via the carotid artery. The groups were compared in terms of procedural success, time, post-procedural blood pH, lactate levels, and complications. Duct morphology was observed in group 1 as follows: type 1 in 12 patients, type 3 in 8, type 2 in 2, and type 6 in 1 patient. In group 2, 26 patients had type 3, 1 had type 2, and 1 had type 6. The tortuosity index of the patients in group 1 was 1 in 8 patients, 2 in 8 patients, and 3 in 7 patients, while in group 2, it was 1 in 5 patients, 2 in 15 patients, and 3 in 8 patients. The success rate was 69.6% (16/26) in group I and 93.5% (29/31) in group II (P=.030). The cumulative success rate was 88.2% (45/51). The procedural durations were 78.2 ± 34.1 and 52.1 ± 22.0 minutes in group I and group II, respectively (P=.002). The mean blood pH values upon the completion of the procedure were 7.26 ± 0.1 and 7.33 ± 0.0 in group I and group II, respectively (P=.038). The mean post-procedural lactate levels were 2.8 mmol/L and 2.3 mmol/L in group I and group II, respectively (P=.038). The 2 groups did not show any differences in terms of procedural complications. The carotid artery route can be preferred, especially in vertical and tortuous ductus arteriosus, as it is associated with a high success rate and a short procedural time, as well as a better metabolic condition after the procedure.

The murine male reproductive organ at a glance: Three-dimensional insights and virtual histology using label-free light sheet microcopy.

The unique anatomy of the male reproductive organ reflects its complex function from sperm maturation to their storage for months until emission. Since light microscopy in two dimensions (2d) cannot sufficiently demonstrate its complex morphology, a comprehensive visualization is required to identify pathologic alterations in its entire anatomical context. Aim of this study was to use three-dimensional (3d) light sheet fluorescence microscopy (LSFM) to visualize entire murine testes in 3d, label-free and at subcellular resolution, and to assign local autofluorescence to testicular and deferent structures. Murine testes were fixed with four different fixatives and subsequently cleared with benzoic acid/benzyl benzoate. Hereafter, complete murine testes were scanned with LSFM with different fluorescence filter sets and subsequently embedded in paraffin for further conventional planar histology. Autofluorescence signals of the murine reproductive organ allowed the unambiguous identification of the testicular anatomy from the seminiferous tubules to the vas deferens with their specific stratification independent of the used fixative. Blood vessels were visualized from the pampiniform plexus to the small capillaries of single tubules. Moreover, due to the specific intrinsic fluorescence properties of the efferent ducts and the epididymis, luminal caliber, the epithelial stratification and retronuclear cytoplasmic inclusions gave a unique insight into the interface of both morphological structures. Subsequent 2d histology confirmed the identified morphological structures. LSFM analysis of the murine reproductive organ allows due to its intrinsic fluorescence a simple, label-free 3d assessment of its entire duct morphology, the epithelial composition, and the associated blood supply in its anatomical relation. LSFM provides the technical basis for comprehensive analyses of pathologically altered murine testes in its entirety by depicting specific autofluorescence. Thereby it facilitates mouse studies of testicular disease or their drug-related alterations in more detail potentially for clinical translation assessing human testicular biopsies.

Segmental Versus Diffuse Main Duct Intraductal Papillary Mucinous Neoplasm: Examination of Main Pancreatic Duct Morphology and Implications for Malignancy Risk and Extent of Surgical Resection.

To determine whether the morphologic features of the main pancreatic duct (MPD) of main-duct-involved-intraductal papillary mucinous neoplasm (IPMN) (ie, main duct or mixed main duct/side branch) have implications for the risk of malignancy and extent of resection. International consensus guidelines acknowledge the presence of various MPD morphologies (ie, diffuse vs segmental main-duct-involved-IPMN) without a precise definition of each entity and with limited data to guide treatment strategy. All consecutive main-duct-involved-IPMN patients (2005-2019) with a MPD diameter ≥5mm by cross-sectional imaging were reviewed from a prospective institutional database. Morphologic features of the MPD were correlated with the identification of high-grade dysplasia or pancreatic ductal adenocarcinoma (HGD/PDAC) by logistic regression modeling. In patients who underwent partial pancreatectomy, preoperative MPD morphologic features were correlated with the future development of HGD/PDAC in the pancreatic remnant by Cox hazards modeling. In a cohort of 214 main-duct-involved-IPMN patients, the overall rate of HGD/PDAC was 54.2%. MPD morphologic characteristics associated with HGD/PDAC included: maximal MPD diameter (5-10mm: 29.8%; 10-14mm: 59.0%; 15-19mm: 78.6%; ≥20mm: 95.8%; P <0.001), segmental extent of maximal dilation (<25%: 28.2%; 25%-49%: 54.9%; 50%-74%: 63.1%; ≥75%: 67.9%; P =0.002), and nonsegmental MPD diameter (<5mm: 21.5% vs ≥5mm: 78.5%, P <0.001). Diffuse MPD dilation involving ≥90% extent was rare (5.6%). After a median follow-up of 50 months, 7 (7.2%) patients who underwent partial pancreatectomy for IPMN without associated PDAC developed HGD/PDAC in the pancreatic remnant. Maximal MPD diameter, segmental extent of maximal dilation, or nonsegmental MPD diameter were not associated with the development of HGD/PDAC in the pancreatic remnant. However, a mural nodule on preoperative imaging was associated with the development of HGD/PDAC in the pancreatic remnant. "Diffuse" involvement with homogenous dilation of the MPD was rare. For the majority of patients with segmental main-duct-involved-IPMN, the MPD morphology conferred malignancy risk. Duct morphology was not predictive for the development of HGD or invasive disease in the pancreatic remnant, implying the safety of limited pancreatic resection for initial surgical management.

Changes of thoracic duct flow and morphology in an animal model of elevated central venous pressure

Objective: Investigation of lymph fluid dynamics in thoracic duct during central venous pressure elevation. Background: Lymphatic flow is affected by elevated central venous pressure (CVP) in congestive heart failure. The changes of thoracic duct (TD) lymph flow have not been studied chronically in the setting of elevated CVP. This study is to investigate fluid dynamics and remodeling of the TD in the elevated CVP animal model. Methods: A flow probe was implanted on the swine TD (n = 6) and tricuspid regurgitation (TR) was created by cutting tricuspid chordae percutaneously. Six swine were used as control group animals. The TD flow was measured for 2 weeks (baseline) before TR and 4 weeks postop-TR surgery. Arterial pressure and CVP were measured. The pressure and flow in the TD were measured percutaneously. Histological and morphological analyses were performed. Results: TR resulted in an increase in CVP from 4.2 ± 2.6 to 10.1 ± 4.3 mmHg (p < 0.05). The lymph flow in the TD increased from 0.78 ± 1.06 before TR to 8.8 ± 4.8 ml/min (p < 0.05) 2 days post-TR and remained plateau for 4 weeks, i.e., the TD flow remained approximately 8–11 fold its baseline. Compared to the 8.1 ± 3.2 mmHg control group, the TD average pressures at the lymphovenous junction increased to 14.6 ± 5.7 mmHg in the TR group (p < 0.05). The TD diameter and wall thickness increased from 3.35 ± 0.37 mm and 0.06 ± 0.01 mm in control to 4.32 ± 0.57 mm and 0.26 ± 0.02 mm (p < 0.05) in the TR group, respectively. Conclusion: The elevated CVP results in a significant increase in TD flow and pressure which causes the TD’s outward remodeling and thickening. Our study implicates that the outward remodeling may result in the TD valve incompetence due to failure coaptation of leaflets.

Analysis of Lacrimal Duct Morphology from Cone-Beam Computed Tomography Dacryocystography in a Japanese Population.

PurposeThe dacryoendoscope is a practical instrument for the examination and the treatment of lacrimal duct obstruction. Nevertheless, as it is a rigid fiberscope, manipulation of the endoscope is somewhat affected by the patient’s lacrimal duct alignment and the skeletal structure of the face. The morphology and inclination of the lacrimal duct vary among individuals and ethnic groups. We aimed to evaluate the alignment of the lacrimal duct from the perspective of endoscopic maneuverability in a Japanese population.MethodsThis retrospective study analyzed the cone-beam computed tomography dacryocystography (CBCT-DCG) images of 102 patients diagnosed with unilateral primary acquired nasolacrimal duct obstruction (PANDO) at Ehime University Hospital from December 2015 to May 2021. The following parameters of the lacrimal duct on the contralateral side of unilateral PANDO were investigated: (1) angle formed by the superior orbital rim–internal common punctum–nasolacrimal duct opening, (2) angle formed by the lacrimal sac and the nasolacrimal duct, (3) length of the lacrimal sac, and (4) length of the nasolacrimal duct.ResultsMeasurements of the above parameters were (1) 10.2° ± 7.8° (range, −11° to +27°), (2) −6.3° ± 14.1° (range, −43° to +40°), (3) 8.9 ± 2.3 mm (range, 4.3–17.1), and (4) 13.2 ± 2.7 mm (range, 5.7–20.7), respectively. The Shapiro–Wilk test demonstrated that the values of all parameters, except (3), followed a normal distribution (p = 0.55, 0.30, 0.0002, and 0.39, respectively). No significant difference was found between the female and male groups (p > 0.05).ConclusionThis study reported anthropometric analysis data of the morphology of the lacrimal ducts using CBCT-DCG in a Japanese population. In our cohort, the line from the superior orbital rim through the internal common punctum to the nasolacrimal duct opening inclined anteriorly in 92% of the patients.

Margin between success and failure of PDA stenting for duct-dependent pulmonary circulation.

Percutaneous patent ductus arteriosus (PDA) stenting is a therapeutic modality in patients with duct-dependent pulmonary circulation with reported success rates from 80-100%. The current study aims to assess the outcome and the indicators of success for PDA stenting in different ductal morphologies using various approaches. A prospective cohort study from a single tertiary center presented from January 2018 to December 2019 that included 96 consecutive infants with ductal-dependent pulmonary circulation and palliated with PDA stenting. Patients were divided according to PDA origin into 4 groups: Group 1: PDA from proximal descending aorta, Group 2: from undersurface of aortic arch, Group 3: opposite the subclavian artery, Group 4: opposite the innominate/brachiocephalic artery. The median age of patients was 22 days and median weight was 3 kg. The procedure was successful in 78 patients (81.25%). PDA was tortuous in 70 out of 96 patients. Femoral artery was the preferred approach in Group 1 (63/67), while axillary artery access was preferred in the other groups (6/11 in Group 2, 11/17 in Group 3, 1/1 in Group 4, P <0.0001). The main cause of procedural failure was inadequate parked coronary wire inside one of the branch of pulmonary arteries (14 cases; 77.7%), while 2 cases (11.1%) were complicated by acute stent thrombosis, and another 2 cases with stent dislodgment. Other procedural complications comprised femoral artery thrombosis in 7 cases (7.2%). Patients with straight PDA, younger age at procedure and who had larger PDA at pulmonary end had higher odds for success (OR = 8.01, 2.94, 7.40, CI = 1.011-63.68, 0.960-0.99, 1.172-7.40,respectively, P = 0.048, 0.031,0.022 respectively). The approach for PDA stenting and hence the outcome is markedly determined by the PDA origin and morphology. Patients with straight PDA, younger age at procedure and those who had relatively larger PDA at the pulmonary end had better opportunity for successful procedure.

Stalling interkinetic nuclear migration in curved pseudostratified epithelium of developing cochlea.

The bending of epithelial tubes is a fundamental process in organ morphogenesis, driven by various multicellular behaviours. The cochlea in the mammalian inner ear is a representative example of spiral tissue architecture where the continuous bending of the duct is a fundamental component of its morphogenetic process. Although the cochlear duct morphogenesis has been studied by genetic approaches extensively, it is still unclear how the cochlear duct morphology is physically formed. Here, we report that nuclear behaviour changes are associated with the curvature of the pseudostratified epithelium during murine cochlear development. Two-photon live-cell imaging reveals that the nuclei shuttle between the luminal and basal edges of the cell is in phase with cell-cycle progression, known as interkinetic nuclear migration, in the flat region of the pseudostratified epithelium. However, the nuclei become stationary on the luminal side following mitosis in the curved region. Mathematical modelling together with perturbation experiments shows that this nuclear stalling facilitates luminal-basal differential growth within the epithelium, suggesting that the nuclear stalling would contribute to the bending of the pseudostratified epithelium during the cochlear duct development. The findings suggest a possible scenario of differential growth which sculpts the tissue shape, driven by collective nuclear dynamics.