Search Results (68)

Background and Aims: An appropriate surveillance system must be established to efficiently identify cases of intraductal papillary mucinous neoplasm (IPMN)-related malignant transformation. We analyzed the initial clinical background that affects long-term prognosis and narrowed the population for whom continued evaluation is inevitable. Methods: We included 1645 patients with IPMN treated at our hospital since 2010. We examined the types and timing of malignant transformation in terms of the worrisome features (WFs). The chi-squared test, log-rank test, and Cox proportional hazards model were used for the analysis (statistical significance at α = 0.05). Results: In total, 123 (7.5%) and 41 patients (2.5%) had IPMN-derived carcinoma (IPMN-DC) and concomitant pancreatic ductal adenocarcinoma (c-PDAC), respectively. Compared with IPMN-DC, a significantly higher proportion of c-PDAC patients were diagnosed with an advanced disease stage that developed earlier. The factors with significantly shorter time for IPMN-DC development were maximum cyst diameter (MCD) ≥ 30 mm, nonbranched type, main pancreatic duct (MPD) diameter ≥ 5 mm, and septal nodal structure (SNS) for IPMN-DC, and MCD ≥ 30 mm, main duct type, MPD ≥ 5 mm, SNS, cyst enlargement (≥2.5 mm/year), and abnormal CA19-9 levels for c-PDAC. Both groups could be significantly stratified by the number of WFs. A relative risk analysis revealed that SNS, MCD ≥ 30 mm, and MPD ≥ 5 mm were significant factors for IPMN-DC, whereas abnormal CA19-9 and SNS were significant for c-PDAC. Conversely, significantly more patients exhibiting these factors initially later developed IPMN-DC or c-PDAC. Conclusions: Ten percent of IPMN cases will develop IPMN-DC or c-PDAC, thereby requiring careful follow-up, especially in cases with SNS, abnormal CA19-9, and MCD ≥ 30 mm. Full article

Background/Objectives: Patients with inflammatory bowel disease (IBD) are at an increased risk of various cancers; such as colorectal cancer; skin cancer; bile duct cancer; or lymphoma; with IBD itself not being the sole cause. Inappropriate or ineffective IBD therapy with a continuous inflammatory burden within the gut leads to an increased risk of malignancy. Our study aimed to investigate the risk of malignancy in our patient cohort; focusing on concomitant therapy; disease duration; and inflammatory burden. Methods: A total of 333 consecutive adult patients with IBD (Crohn’s disease; ulcerative colitis; and IBD unclassified) were included in this study. Data from patients were collected retrospectively using patient charts. The patients were treated in the gastroenterological outpatient clinic of the University Hospital of Augsburg; Germany; between 1 January 2014 and 31 December 2018. Results: The study group included 333 patients; 32 (9.61%) of whom suffered from malignancy (any form). Men (n = 21; 65.62%) tended to develop malignancy more often than women (n = 11; 34.38%, p = 0.051). It was also observed that the probability of developing cancer was 2.40 times higher in male patients than in female patients in our cohort. However, this trend was non-significant (HR = 2.412; p = 0.075). Furthermore; the probability of developing cancer increased with the increasing age at the time of the first diagnosis of IBD (HR = 1.088; p < 0.025). A total of 20 patients (6.00%) received their cancer diagnosis after being diagnosed with IBD. The majority of those patients had skin (n = 6; 30.00%) or colon cancer (n = 5; 25.00%). Other diseases such as CML; NHL; HL; HCC; liver sarcoma; prostate cancer; breast cancer; seminoma; thyroid cancer (a second cancer in one of the patients); or CUP syndrome/lung cancer were diagnosed in single patients. Patients with IBD and colon cancer (n = 5; 25.00%) shared some of the known risk factors for tumour development; such as a long-lasting IBD (n = 5; 100.00%), diagnosis at a young age (under 30; n = 3; 60.00%), and the coexistence of PSC (n = 1; 20.00%). The cancer prevalence rate was relatively low in our cohort despite the use of diverse biologics and immunosuppressive drugs. Faecal calprotectin was confirmed as a relevant tool for inflammation monitoring in this cohort. Conclusions: In our study cohort; we could show a low prevalence rate of malignancy in IBD. There were more malignancies in men and in patients who were diagnosed with IBD at later ages. It can be observed that the prevalence rate of cancer was relatively low despite the use of diverse biologics and immunosuppressive drugs; which is the major conclusion of this study. Additionally; the known correlation between elevated levels of faecal calprotectin and gut inflammation was confirmed through our statistical analysis. The use of calprotectin as a non-invasive screening tool for gut inflammation is advised. Full article

Background/Objectives: Diagnosing biliary obstructions is challenging, especially when histopathology is inconclusive. Non-malignant biliary strictures often require additional tests and a personalized approach. This study investigates the prevalence, characteristics, and natural history of indeterminate biliary strictures. Methods: A retrospective analysis was conducted on 510 treatment-naive patients with hyperbilirubinemia due to biliary strictures or obstruction, who were all candidates for endoscopic retrograde cholangiopancreatography (ERCP). Patients with a known etiology before the procedure were excluded. Diagnosis was made via brush cytology or intraductal biopsy during ERCP, with follow-up for indeterminate cases. Statistical analysis was performed with Statistica software (version 13.3; TIBCO Software Inc. (2017), Palo Alto, CA, USA). Results: Out of 510 patients, 186 (36.5%) had non-malignant biliary strictures. Strictures were located in the liver hilum (29.6%), common bile duct (11.8%), and peripancreatic ducts (58.1%). Follow-up ERCP identified malignancy in 21.5% of cases initially deemed benign. Non-malignant causes were confirmed in 41.4% of initially benign strictures, while 37.1% remained indeterminate. After six months, 25.8% of cases remained unresolved. Conclusions: A quarter of benign biliary strictures remain indeterminate despite follow-up, and 20% are later identified as malignant. Improved diagnostic protocols are needed to better manage and expedite the diagnosis of indeterminate biliary strictures. Full article

Background: Glucagon-like peptide-2 (GLP-2) is a gut hormone secreted in response to nutrient intake and regulates lipid metabolism in the gut. The present study aims to elucidate the underlying mechanism of GLP-2 in stimulating gut lipid secretion in the fasted state by testing whether GLP-2 signals through the brain’s GLP-2 receptor and melanocortin 4 receptor (MC4R). Methods: Sprague-Dawley rats were implanted with a mesenteric lymph duct cannula for measuring gut lipid secretion and an intracerebroventricular cannula for infusion of a GLP-2R antagonist (GLP-2(11-33)), an MC4R antagonist (SHU9119), or saline as a control. The rat received a lipid infusion into the small intestine and a peritoneal injection of GLP-2 five hours later. Results: Brain administration of a GLP-2R antagonist or an MC4R antagonist attenuated the stimulatory effects of peripheral GLP-2 on lymph triglyceride output. These effects were associated with differential changes in the expression of key genes in jejunal endothelial cells, smooth muscle cells, and neuronal cells. Conclusions: These results support the involvement of central GLP-2R and MC4R in a neural pathway for GLP-2 to mobilize lipids stored in the gut during the post-absorptive state. Full article

Ciliopathies are disorders that affect primary or secondary cellular cilia or structures associated with ciliary function. Primary cilia (PC) are essential for metabolic regulation and embryonic development, and pathogenic variants in cilia-related genes are linked to several pediatric conditions, including renal-hepatic diseases and congenital defects. Biliary atresia (BA) is a progressive infantile cholangiopathy and the leading cause of pediatric liver transplantation. Although the exact etiology of BA remains unclear, evidence suggests a multifactorial pathogenesis influenced by both genetic and environmental factors. Patients with BA and laterality defects exhibit genetic variants associated with ciliopathies. Interestingly, even isolated BA without extrahepatic anomalies presents morphological and functional ciliary abnormalities, suggesting that environmental triggers may disrupt the ciliary function. Among these factors, hypoxia has emerged as a potential modulator of this dysfunction. Hypoxia-inducible factor 1-alpha (HIF-1α) plays a central role in hepatic responses to oxygen deprivation, influencing bile duct remodeling and fibrosis, which are key processes in BA progression. This review explores the crosstalk between hypoxia and hepatic ciliopathies, with a focus on BA. It discusses the molecular mechanisms through which hypoxia may drive disease progression and examines the therapeutic potential of targeting hypoxia-related pathways. Understanding how oxygen deprivation influences ciliary function may open new avenues for treating biliary ciliopathies and improving patient outcomes. Full article

Mucinous cystic neoplasm of the liver (MCN-L) is a rare benign tumor accounting for less than 5% of all liver cysts, with MCN-L in the hilar region being exceptionally uncommon and often misdiagnosed due to its complex presentation. A 48-year-old woman presented with obstructive jaundice following initial laparoscopic drainage of hepatic cysts, where pathology initially indicated benign cystic lesions. Months later, imaging revealed an enlarged cystic lesion in the left liver lobe with intrahepatic bile duct dilation. Further evaluations, including ultrasound, enhanced CT, and MRI, confirmed a large cystic lesion compressing the intrahepatic bile ducts. After a multidisciplinary discussion, hepatic cyst puncture and drainage were performed, temporarily alleviating jaundice. However, she returned with yellowish-brown drainage fluid and worsening jaundice, prompting cyst wall resection. Postoperative pathology confirmed MCN-L. Three months later, jaundice subsided, and a hepatic resection of segment 4 was performed, with pathology confirming low-grade MCN-L. At a 12-month follow-up, the patient showed no abnormalities. This case highlights the diagnostic and therapeutic challenges of MCN-L in the hilar region, as it can easily be mistaken for other liver cystic lesions on imaging. Pathologic examination is essential for definitive diagnosis, and early radical surgical resection is critical to improve prognosis and reduce the risk of malignancy and recurrence. Full article

Mammary intraductal macrophages (foam cells) in humans are the most commonly encountered cells in spontaneous breast nipple discharge, nipple aspirate fluid, and ductal lavage, yet their origin remains unproven. These cells, in both humans and murine model systems, increase in pregnancy, pseudopregnancy, and other conditions like proliferative fibrocystic disease and intraductal neoplasia, ductal carcinoma in situ (DCIS), where there is intraductal ectasia and obstruction. Previous immunocytochemical studies with macrophage (CD68, lysozyme), epithelial (cytokeratin, estrogen receptor), and myoepithelial (smooth muscle actin, CALLA, maspin) markers have indicated that intraductal foam cells are of macrophage lineage. These foam cells engage in phagocytosis of both endogenous and exogenous substances present within the ducts and are not proliferative. Although it has been suggested that foam cells could derive from tissue-specific and niche-specific precursors or circulating monocytes, to date no experimental nor clinical studies have provided direct proof of their origin. In this study, we provide evidence in both human and murine bone marrow transplant studies that intraductal foam cells are bone marrow-derived. We first studied a registry of sex-mismatched bone marrow transplant recipients who later in life had undergone breast biopsies for either proliferative fibrocystic disease, DCIS, or gynecomastia, and studied these biopsies by XY chromosome fluorescence in situ hybridization (FISH) and informative microsatellite polymorphic markers. The intraductal foam cells were of bone marrow donor-origin. Then, in the experimental bone marrow transplant murine studies, donor marrow from female ROSA26 containing the lacZ reporter were transplanted into either irradiated female recipient transgenic mice carrying the highly penetrant MMTV-pymT or FVB/N background mice, where induced pluripotent stem (iPS) cells derived from tail vein fibroblasts of FVB/N-Tg(MMTV-PyVT)634Mul/J mice were subsequently injected into their mammary fat pads. In all of the transplanted recipient mice, the intraductal foam cells expressed the β-galactosidase (lacZ) reporter and also co-expressed markers of myeloid–macrophage lineage. The number of donor-derived intraductal foam cells increased in pseudopregnancy 5-fold and in intraductal neoplasia 10-fold. Although macrophages of different origins and lineages are undoubtedly present within both the murine and human breasts, those macrophages that qualify as phagocytic intraductal foam cells are bone marrow-derived. Full article

Background and clinical significance: Phyllodes tumors (PTs) are rare stromal neoplasms originating in the connective tissue of the breast, distinct from carcinomas that arise from the ducts or lobules. These tumors exhibit a broad spectrum of morphologic features and are traditionally classified as benign, borderline, or malignant. Case presentation: We present the case of a 71-year-old female diagnosed with a malignant PT and treated at our hospital. The patient noticed a gradually enlarging lump in her right breast over several months. Mammography was inconclusive, but an ultrasound later revealed a lobulated, firm mass, classified as BIRADS 5. Physical examination identified a 20 cm mass, and core needle biopsy suggested a borderline PT. Following lumpectomy, pathology confirmed a malignant tumor with narrow surgical margins (0.1 cm). Although mastectomy was recommended to achieve wider margins, the patient opted for adjuvant radiotherapy. She received 50 Gy in 25 fractions to the whole breast, followed by a 16 Gy boost to the tumor bed in 8 fractions. The treatment was well tolerated and completed successfully. Initially, the patient’s therapeutic management was delayed due to a combination of personal and organizational factors. However, the process was later streamlined through the use of a novel digital tool developed to facilitate the entire patient journey within our hospital system. Conclusions: This case highlights the diagnostic complexities of PTs, the critical need for effective collaboration between specialties, and the importance of timely treatment planning for optimal patient outcomes. Full article

The ectopic thyroid gland is an abnormal development of the embryo. Most of the ectopic thyroid occurs in the path around the thyroglossal duct or on the lateral side of the neck. However, ectopic thyroid occurs in the heart, which is rare. We report a case of right ventricular ectopic thyroid. This case highlights the imaging characteristics of computed tomography (CT) and cardiac magnetic resonance (CMR) and discusses the underlying mechanisms for a timely diagnosis. Full article

Biliary atresia (BA) is an obliterative disease of the bile ducts affecting between 1 in 10,000–20,000 infants with a predominance in Asian countries. It is clinically heterogeneous with a number of distinct variants (e.g., isolated, Biliary Atresia Splenic Malformation syndrome, Cat-eye syndrome, cystic BA, and CMV-associated BA). Facts about its aetiology are hard to encounter but might include genetic, developmental, exposure to an environmental toxin, or perinatal virus infection. However, the cholestatic injury triggers an intrahepatic fibrotic process beginning at birth and culminating in cirrhosis some months later. Affected infants present with a triad of conjugated jaundice, pale stools, and dark urine and may have hepatosplenomegaly upon examination, with later ascites coincident with the onset of progressive liver disease. Rapid, efficient, and expeditious diagnosis is essential with the initial treatment being surgical, typically with an attempt to restore the bile flow (Kasai portoenterostomy (KPE)) or primary liver transplantation (<5%) if considered futile. Failure to restore bile drainage or the onset of complications such as recurrent cholangitis, treatment-resistant varices, ascites, hepatopulmonary syndrome, and occasionally malignant change are usually managed by secondary liver transplantation. This issue summarises recent advances in the disease and points a way to future improvements in its treatment. Full article

Background and objectives: Laparoscopic cholecystectomy (LC) is the most commonly performed operation in general surgery in the Western World. Gallbladder surgery, although most of the time simple, always offers the possibility of unpleasant surprises. Despite progress, the incidence of common bile duct injury is 0.2–0.4%, causing devastating implications for the patient and the surgeon. This is mainly due to the failure to identify the normal anatomy properly. The literature review reveals a lack of structured knowledge in the surgical anatomy of cholecystectomy. The aim of this study was to develop a framework with a common anatomical language for safe laparoscopic and open cholecystectomy. Materials and Methods: The Hellenic Task Force group on the typology for Safe Laparoscopic Cholecystectomy performed a critical review of the literature on the laparoscopic anatomy of cholecystectomy. The results were compared with those of a clinical study of 279 patients undergoing LC for uncomplicated symptomatic gallstone disease. Results: Fourteen elements encountered during LC under the critical view of safety (CVS) approach were determined. The typical vascular–biliary pedicle with one cystic duct distributed laterally (or caudally) and one cystic artery medially (or cranially) lying at any point of the hepatocystic space was found in 66% of the cases studied. Anatomical schemata were formulated corresponding to the norm and four variations. Conclusions: The proposed cognitive anatomical schemata summarize simply what one can expect in terms of deviation from the norm. We believe that the synergy between the correct application of the CVS and the structured knowledge of the surgical anatomy in cholecystectomy helps the surgeon to handle non-typical structures safely and to complete the laparoscopic or open cholecystectomy without vascular–biliary injuries. Full article

Introduction: Persistent Müllerian duct syndrome (PMDS) is a rare disorder of sex development (DSD) caused by mutations in the genes coding anti-Müllerian hormone (AMH) or the AMH receptor, characterized by the persistence of Müllerian derivatives, the uterus and/or fallopian tubes, in otherwise normally virilized boys. Testicular regression syndrome is common in PMDS, yet the association with supernumerary testis has been reported in only two patients where genetic testing was not performed. Method: Thus, we report an individual with this particular association caused by a previously unreported homozygous variant in the AMHR2 gene to enable future genotype–phenotype correlations in this rare disorder. In addition, a search of PMDS associated with congenital anomalies reported in the literature was performed to provide a comprehensive overview of this pathology. Results: We present the case of a 13-year-old boy with a history of bilateral cryptorchidism. Two attempts of right orchidopexy were performed at the age of 4 and 5 years. At that time, exploratory laparoscopy identified an intra-abdominal left testicle. In addition, a fibrous structure extending from the left intra-abdominal testicle to the deep inguinal ring (Müllerian duct remnants) and a medially located abdominal mass, bilaterally fixated to the parietal peritoneum (uterine remnant), were detected. The left testicular biopsy revealed immature prepubertal testicular tissue. The uterine remnant was dissected and removed and the left orchidopexy was performed. The karyotype was 46, XY without other numerical or structural chromosomal abnormalities. Reinterventions on the left testicle were performed at the age of 9 and 12 years when a testicular remnant was identified in the left inguinal canal and removed. Three months after left orchidectomy, ultrasound followed by abdominopelvic MRI identified a structure resembling a testis in the left inguinal area. Another surgical exploration was performed, and a mass located outside (lateral) the inguinal canal was found. A biopsy from the suspected mass was performed. The histopathologic examination showed characteristics of immature prepubertal testis. The patient was later referred to our clinic with the suspicion of DSD. Serum AMH and inhibin B were normal. Therefore, the diagnosis of PMDS was suspected. Genetic testing was performed using next-generation sequencing in a gene panel that included AMH and AMHR2 genes. A homozygous variant classified as likely pathogenic in the AMHR2 gene was identified but remains unreported in the literature (NC_000012.11:g.53823315T>C in exon 8 of the AMHR2 gene). Conclusions: A high degree of suspicion and awareness is needed to diagnose this condition in order to avoid iterative surgery. The coexistence of two extremely rare conditions (PMDS and supernumerary testes) has been reported previously in only two patients, yet the association could have a common pathophysiologic background. Our case, reporting a novel AMHR2 variant, highlights the importance of genetic testing in these individuals in order to elucidate a possible genotype–phenotype correlation. Full article

The males of Carabus lefebvrei produce sperm bundles of quite variable size as a consequence of a sexual selection via sperm competition. The ultrastructural features of spermatogenesis of the species and the sequence of events leading to sperm bundle formation along the deferent duct lumen revealed the origin and evolution of the apical structure protecting the sperm bundles. Elongated layers of the electron-dense material of variable size and thickness are visible over the microvilli of the distal deferent duct epithelium. They likely correspond to sections through different levels of discoidal secretions. Then, the sperm present in the duct lumen attach to one side of such elongated secreted structures. Later on, these structures bent to take a cap shape and increase their size and thickness by apposition of additional secretions produced by the proximal deferent duct epithelium. These results reconcile the different opinions about the formation of the structures called the cap and the rod (spermatostyle). In our work, we in fact obtained evidence that both these structures have the same origin, even though at the end of their formation they exhibit a different appearance. The reported results indicate that, differently from the spermatostyle, in the initial stages of cap formation, the sperm adhere only to one side of the cap rather than around the whole structure, as it occurs instead along the spermatostyle rod. Under this aspect, the cap structure is similar to the protection present in the sperm of some whirligig beetle. Full article

Background/Objectives: Epiphora, or excessive tearing, is a common symptom often attributed to benign conditions such as dry eye or nasolacrimal duct obstruction. However, it can also be an early indicator of lacrimal sac tumors, which are frequently misdiagnosed or diagnosed late due to their subtle presentation. This study aims to identify the clinical features that contribute to delays and misdiagnoses of lacrimal sac tumors in patients presenting with epiphora, with the goal of improving early detection and treatment outcomes. Methods: This retrospective study reviewed medical records from Taipei Veterans General Hospital between 2007 and 2023, focusing on patients who presented with epiphora and were later diagnosed with pathologically confirmed lacrimal sac tumors. Inclusion criteria were limited to cases that were initially misdiagnosed or had a delayed diagnosis, with imaging and clinical evaluations confirming tumor-related tear drainage obstruction. Patients with non-tumor causes of epiphora were excluded. Results: Eleven cases of lacrimal sac tumors were identified, including two benign and nine malignant tumors. The average duration from symptom onset to diagnosis was 22.4 months. Common symptoms included epiphora (100%), discharge (54.5%), and hemolacria (18.2%). Subtle clinical signs, such as asymmetry in the medial canthal region and non-tender swelling, were frequently noted. Despite receiving appropriate surgical and adjuvant treatments, the impact of delayed diagnosis was significant. Two patients succumbed to tumor-related disease; one developed lung metastasis 12 years after diagnosis, and another experienced recurrence during a six-year follow-up after undergoing extensive exenteration, adjuvant chemotherapy, and radiotherapy. Conclusions: Lacrimal sac tumors can present insidiously with symptoms often mistaken for benign conditions, leading to significant diagnostic delays. Thorough history taking, meticulous physical examination, and timely imaging are crucial for early detection. Increased clinician awareness and a high index of suspicion for lacrimal sac tumors in patients with atypical epiphora are essential to improve prognosis and reduce the risk of severe outcomes. Full article

In order to find a suitable size of sheath duct and a reliable construction method for precast walls, a cast-in-place and five 1/2 scale precast drift-hardening concrete walls reinforced with weakly bonded ultra-high strength SBPDN rebars were fabricated and tested under reserved lateral load and constant compression. The experimental variables were the diameter of sheath ducts (45 mm, 100 mm, and 120 mm), embedded length (20d and 35d; d is the nominal diameter of SBPDN rebars), axial load ratio (0.075 and 0.15), and the construction method. The experimental observations, hysteresis behaviors, envelope curves, residual deformation, crack propagation, and energy dissipation were compared in the study. Moreover, a formula was applied to calculate the bond strength of the sheath duct. The experimental and calculated results revealed that increasing the axial load ratio and embedment length could not enhance the bond strength of the sheath ducts, and increasing the diameter decreased the bond strength significantly. Anchored the SBPDN rebars in smaller sheath ducts separately was a more stable connection method for precast concrete shear walls and provided sufficient drift-hardening capability, even at a large drift level (over 3%). Full article