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Case Report Open Access
Ahmed A. Ahmed, Y. Helen Zhang
Published online January 17, 2025
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Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2024.00037
Abstract
Leishmaniasis is a systemic parasitic disease that can affect unusual sites such as the lungs. We report a case of a 45-year-old male with human immunodeficiency virus infection [...] Read more.

Leishmaniasis is a systemic parasitic disease that can affect unusual sites such as the lungs.

We report a case of a 45-year-old male with human immunodeficiency virus infection who presented with abdominal pain and vomiting. Imaging studies revealed minimal bilateral ground-glass opacities in the lungs, hepatosplenomegaly, and diffuse lymphadenopathy. A bronchoscopy with bronchoalveolar lavage cytology evaluation showed abundant macrophages containing numerous intracellular organisms with characteristic dot-like kinetoplasts, confirming the diagnosis of Leishmaniasis. Special stains for other infections were negative.

This case highlights the value of bronchoalveolar lavage cytology in diagnosing non-neoplastic lung pathologies, including parasitic infections like Leishmaniasis, thereby enabling prompt and targeted treatment.

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Case Report Open Access
Zhaoyang Yang, Bin Wang, Liang Yang, Xuemin Xue, Jiacong Wei, Liyan Xue
Published online October 30, 2024
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Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2024.00033
Abstract
Paget’s disease of the esophagus is extremely rare, with few cases reported. In this report, we describe a case of recurrent esophageal Paget’s disease coexisting with small cell [...] Read more.

Paget’s disease of the esophagus is extremely rare, with few cases reported. In this report, we describe a case of recurrent esophageal Paget’s disease coexisting with small cell carcinoma. A 63-year-old man presented with the chief complaint of a rediscovered early esophageal cancer. Endoscopic examination revealed two separate superficial flat tumors in the upper and mid esophagus. Endoscopic submucosal dissection was performed, diagnosing diffuse Paget’s disease (5.5 × 3.5 cm) and a small focus on intramucosal squamous cell carcinoma, respectively. Paget’s cells were also found in the distal and right margins of the first specimen of endoscopic submucosal dissection. Immunohistochemical analysis showed that Paget’s disease diffusely expressed cytokeratin 7 (CK7), CK18, and mucin 6 (MUC6), and focally expressed CD56 and chromogranin A, but not CK5/6, p63, p40, MUC5AC, MUC2, or synaptophysin. A complete absence of p53 and Rb1 was observed in Paget’s disease. However, overexpression of p53 and retention of Rb1 were seen in squamous cell carcinoma. Approximately 27 months later, a prominent tumor was found at the same location as the previous Paget’s disease. Subsequently, radical surgery was performed, and the final pathological evaluation revealed esophageal small cell carcinoma coexisting with Paget’s disease. Moreover, both p53 and Rb1 were completely absent in both Paget’s disease and the small cell carcinoma. This suggests that esophageal Paget’s disease may dedifferentiate and develop into small cell carcinoma. In conclusion, esophageal Paget’s disease can co-occur with invasive carcinomas, including small cell carcinoma, and should be completely resected endoscopically, with close follow-up.

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Letter to the Editor Open Access
Javier Guinea-Castañares, Jesus Maria Iturralde Iriso, Irune Natalia Elizondo Pinillos, Gloria Martinez Iniesta
Published online September 13, 2024
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00219
Original Article Open Access
Xing Liu, Fengyang Chen, Zhaozhe Liu, Mingyu Duan, Ye Gu, Xuan Liang, Xiaofeng Wu, Cheng Lv, Xinyue Li, Jiamin Qian, Meiyuxi Li, Linge Zhang, Tianyue Chen, Yan Wang, Guoliang Chen
Published online August 30, 2024
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Future Integrative Medicine. doi:10.14218/FIM.2024.00022
Abstract
Albumin is a major prognostic factor for patients with advanced liver disease, dependent on its concentration and biological activity. This study aimed to improve the method of [...] Read more.

Albumin is a major prognostic factor for patients with advanced liver disease, dependent on its concentration and biological activity. This study aimed to improve the method of active albumin detection and elucidate its predictive validity of albumin activity across hepatic disease progression and etiology.

This study synthesized a novel ratiometric fluorescent probe with an improved structure of 2′-FBPBN. The technique was used to detect native human albumin (HA) activity in 244 patients with hepatitis B cirrhosis (LC) and 66 patients with hepatocellular carcinoma (HCC). Clinical and laboratory data were also collected.

Patients with LC and HCC were divided into normal albumin and low albumin (LA) groups. The median levels of albumin and HA activity in LC patients were 41.44 g/L and 51.85%, 28.51 g/L and 53.89%, respectively, while in HCC patients, they were 43.19 g/L and 33.69%, 30.77 g/L and 43.63%, respectively. The levels of total bilirubin, prothrombin time, international normalized ratio, native HA activity, Child-Pugh score, model for end-stage liver disease score, and model for end-stage liver disease-Na score were significantly higher in the LA groups, while the levels of platelet, cholesterol, and cholinesterase were lower compared to the normal albumin group (P < 0.05). The LA groups were more likely to suffer from hepatic encephalopathy and ascites. Patients with normal active HA had significantly higher survival rates than those with low active HA.

Native HA activity may outperform albumin as a prognostic indicator for assessing the severity of liver disease.

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Mini Review Open Access
Hongyan Liu, Hao Ai, Ying Liu
Published online March 30, 2025
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Oncology Advances. doi:10.14218/OnA.2024.00034
Abstract
Endometrial cancer (EC) is one of the most prevalent malignancies of the female reproductive system and ranks among the three primary types of gynecological cancers. Recent trends [...] Read more.

Endometrial cancer (EC) is one of the most prevalent malignancies of the female reproductive system and ranks among the three primary types of gynecological cancers. Recent trends indicate a rising incidence of EC in younger patients, highlighting the urgent need for effective early screening strategies. This review examines the challenges associated with early diagnosis and screening, including ambiguous methodologies (e.g., transvaginal ultrasound: sensitivity 80–90%, specificity 60–70%), undefined target populations, and the absence of efficient, cost-effective, minimally invasive solutions (e.g., cytology sensitivity ≤50% in community settings). The article provides an overview of the current landscape and emerging innovations in universal EC screening, highlighting advancements in early detection and diagnosis, such as DNA methylation panels (sensitivity 89–94%, specificity 91–97% in phase II trials) and vibrational spectroscopy (sensitivity 92%, specificity 88% in pilot studies). Additionally, future directions for implementing effective screening strategies are explored, emphasizing the potential of high-accuracy biomarkers and scalable technologies to reduce mortality and healthcare costs.

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Original Article Open Access
Lin Zhang, Li Gan, Yuru Lin, Zhechuan Mei, Shengtao Liao
Published online April 18, 2025
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00007
Abstract
Fat mass and obesity-associated protein (FTO) has been linked to various cancers, though its role in hepatocellular carcinoma (HCC) remains unclear. This study aimed to investigate [...] Read more.

Fat mass and obesity-associated protein (FTO) has been linked to various cancers, though its role in hepatocellular carcinoma (HCC) remains unclear. This study aimed to investigate FTO expression, its clinical relevance, functional role in HCC progression, and the underlying molecular mechanisms.

Quantitative reverse-transcription polymerase chain reaction and immunohistochemical analysis were used to assess FTO expression in HCC. Functional assays, including proliferation, invasion, and epithelial-mesenchymal transition studies, were conducted using HCC cell lines with FTO knockdown. N6-methyladenosine (m6A) RNA immunoprecipitation and RNA stability assays further elucidated the role of FTO in BUB1 mRNA methylation and stability. Co-immunoprecipitation studies were employed to confirm the interaction between BUB1 and TGF-βR1. In vivo studies in nude mice were conducted to evaluate tumor growth following FTO knockdown.

FTO was significantly upregulated in HCC tissues compared to normal liver tissues, with higher expression observed in advanced tumor-node-metastasis stages and metastatic HCC. Elevated FTO correlated with poor overall survival in patients. Silencing FTO decreased HCC cell proliferation, colony formation, invasion, epithelial-mesenchymal transition, and tumor growth in nude mice. Mechanistically, FTO downregulation led to increased m6A modification of BUB1 mRNA, thereby promoting its degradation via the YTH domain family 2-dependent pathway and reducing BUB1 protein levels. Additionally, BUB1 physically interacted with TGF-βR1, activating downstream TGF-β signaling.

FTO is overexpressed in HCC and is associated with poor clinical outcomes. Mechanistically, FTO promotes HCC progression by stabilizing BUB1 mRNA through an m6A-YTH domain family 2–dependent pathway, which activates TGF-β signaling. Targeting the FTO–BUB1–TGF-βR1 regulatory network may offer a promising therapeutic strategy for HCC.

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Review Article Open Access
Nicole M. Anastasio, George Y. Wu
Published online March 14, 2025
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00315
Abstract
Extrahepatic portosystemic shunts (EPS) are abnormal connections between the portal and systemic circulations. Acquired EPS occur most commonly in adults and are usually associated [...] Read more.

Extrahepatic portosystemic shunts (EPS) are abnormal connections between the portal and systemic circulations. Acquired EPS occur most commonly in adults and are usually associated with portal hypertension due to cirrhosis. Acquired EPS cases can be further subdivided into two types: variceal (pre-existing) EPS and non-variceal EPS (NVEPS). Variceal EPS arise from originally small vessels with pre-existing dual portal and systemic drainage. Due to elevated portal pressure, these vessels dilate and undergo a reversal of flow, sending blood back to the systemic circulation. A much less common and, therefore, underappreciated subset of acquired EPS is NVEPS, which consists of aberrant connections that did not previously exist between the portal vein and large systemic vessels, usually in the presence of portal hypertension. Neoangiogenesis results in the development of abnormal anastomoses between the portal vein and other large veins, resulting in splenorenal, gastrorenal, portocaval, and mesocaval shunts. While not uncommon, they are frequently overlooked in the diagnosis and treatment of portal hypertension and can pose significant diagnostic and therapeutic challenges. Because the treatment of variceal EPS and NVEPS can differ markedly, it is important to correctly diagnose NVEPS and institute appropriate management. The aim of this article was to review acquired EPS, with particular attention to NVEPS, updating the pathogenesis, diagnosis, and treatment.

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Original Article Open Access
Biwu Wu, Haoyue Yuan, Qiang Yuan, Gang Wu, Jin Hu
Published online April 3, 2025
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Neurosurgical Subspecialties. doi:10.14218/NSSS.2025.00006
Abstract
Surgical management of supratentorial spontaneous intracerebral hemorrhage (sICH) remains controversial. Craniotomy (CT) reduces mortality but offers limited functional benefits. [...] Read more.

Surgical management of supratentorial spontaneous intracerebral hemorrhage (sICH) remains controversial. Craniotomy (CT) reduces mortality but offers limited functional benefits. Neuroendoscopic surgery (NE) has emerged as a viable alternative, providing improved outcomes. Recent randomized controlled trials (RCTs) strengthen ongoing comparisons between these approaches. This meta-analysis systematically evaluates the efficacy and safety of NE versus CT for supratentorial sICH.

RCTs comparing NE versus CT for supratentorial sICH were systematically identified through comprehensive searches of PubMed, Embase, Cochrane Library, and Web of Science databases. Evaluated outcomes included functional outcome (favorable or unfavorable), hematoma evacuation rate, mortality, intraoperative blood loss, operation time, rebleeding, infection (including pulmonary and intracranial), and total complications. Cochrane’s Risk of Bias-2 tool was employed to assess the risk of bias across the included studies.

Eight RCTs were included, comprising 1,354 patients. NE demonstrated a significant advantage in achieving a favorable functional outcome (risk ratio: 1.43; 95% confidence interval (CI) 1.22, 1.68; p < 0.001) and a notably higher hematoma evacuation rate (mean difference (MD): 7.60; 95% CI 3.59, 11.61; p < 0.001). Additionally, NE was associated with a marked reduction in intraoperative blood loss (MD: −152.95; 95% CI −261.68, −44.22; p = 0.006) and a substantial reduction in operative time (MD: −118.49; 95% CI −147.30, −89.67; p < 0.001). The incidences of unfavorable functional outcome and total complications, including pulmonary infection, were significantly lower in the NE group. However, NE did not lead to an improvement in the mortality rate, and there were no significant differences in the incidences of postoperative rebleeding or intracranial infection between the two groups.

These findings suggest that NE offers distinct advantages in terms of functional outcomes and surgical efficiency for patients with supratentorial sICH. Future studies should involve larger, higher-quality RCTs, and neuroendoscopic techniques should be continuously optimized.

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Systematic Review Open Access
Archana Haria, Jonathon Hill, Kylie J. Mansfield
Published online December 25, 2024
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Oncology Advances. doi:10.14218/OnA.2024.00027
Abstract
Breast cancer is the most common cancer among women, with hormone receptors playing a crucial role, not only in cancer cell growth but also as primary targets in breast cancer treatment. [...] Read more.

Breast cancer is the most common cancer among women, with hormone receptors playing a crucial role, not only in cancer cell growth but also as primary targets in breast cancer treatment. This systematic literature review aimed to summarize the current evidence on estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) discordance rates between primary and recurrent breast cancer. Additionally, it seeks to identify how discordance affects prognosis, metastasis, and the potential evidence of primary tumor heterogeneity.

The databases Web of Science, Scopus, MEDLINE, and PubMed were searched for publications of original research in English from 2013 to 2023. Studies with paired histopathology from primary and recurrent breast cancer that employed immunohistochemistry and fluorescence in situ hybridization were included. Ten studies were deemed eligible for inclusion.

Concordance between primary and recurrent breast cancer was high for ER (80%), PR (65%), and HER2 (85%). Average discordance rates were: ER 19%, PR 34%, and HER2 15%, with PR discordance consistently being the highest. Loss of ER and PR receptors was observed more frequently than gain, while the opposite trend was noted for HER2. Loss of ER and PR was associated with a worse prognosis. Discordance was also observed in cases of tumor metastasis.

Discordance in receptor expression between primary and recurrent breast cancer was common, highlighting the importance of re-biopsy in recurrent or metastatic breast cancer, if possible. Patients who lost hormone receptors experienced worse outcomes, suggesting the development of treatment-resistant tumor clones.

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Mini Review Open Access
Xing Huang, Xiaobing Jiang
Published online March 25, 2025
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Neurosurgical Subspecialties. doi:10.14218/NSSS.2024.00008
Abstract
Pituitary tumors are common intracranial neoplasms that can cause significant morbidity due to hormonal dysregulation and compression of surrounding structures. Despite advancements [...] Read more.

Pituitary tumors are common intracranial neoplasms that can cause significant morbidity due to hormonal dysregulation and compression of surrounding structures. Despite advancements in surgical techniques, challenges persist in treating large, invasive, or recurrent tumors, where complete resection is often difficult. The molecular and genetic mechanisms underlying pituitary tumorigenesis are not yet fully understood, limiting the development of targeted therapies. This review provides a comprehensive overview of recent advancements in neuroendoscopic treatment of pituitary tumors, with a focus on pathogenesis, technological innovations, clinical outcomes, and future directions. We highlight the potential of neuroendoscopic surgery to improve patient outcomes while addressing persistent challenges, such as the steep learning curve and limitations in instrument maneuverability. Future research should prioritize enhancing instrument design, developing 3D and augmented reality visualization systems, and improving training programs to further advance neuroendoscopic techniques.

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