UNASSIGNED: Prostate cancer (PCa) is the most common cancer in men. High-risk PCa is associated with an increased risk of PCa-related death. The combined use of androgen deprivation therapy (ADT) is essential to improve oncological outcomes in patients with high-risk PCa, and relatively long-term ADT administration is preferred when radiotherapy is performed. Meanwhile, whether neoadjuvant therapy for radical prostatectomy (RP) improves oncological outcomes remains controversial. This study aimed to review the oncological outcomes of RP in high-risk PCa and emphasize the significance of neoadjuvant therapy including neoadjuvant hormonal therapy (NHT) and neoadjuvant chemohormonal therapy (NCHT) followed by RP for managing high-risk PCa.
UNASSIGNED: We searched for articles published in the PubMed and Scopus databases from January 1, 2005 to March 30, 2023 using the medical subject headings (MeSH) terms: prostate cancer, prostatectomy, radiation therapy, neoadjuvant therapy, and treatment outcome.
UNASSIGNED: The study on NHT before RP for high-risk PCa found that NHT was associated with reduced adverse pathological features, such as pT3, positive surgical margins (PSM), and lymph node involvement. However, despite shorter operative times and improved surgical outcomes, NHT did not significantly enhance biochemical recurrence (BCR) or other oncological outcomes. The combination therapy using ADT and androgen receptor signaling inhibitors (ARSI) showed varying results. Another investigation explored NCHT with taxane-based agents, indicating acceptable treatment benefits and improved BCR-free survival rates in high-risk PCa patients, demonstrating potential feasibility for this approach. Ongoing trials, like the PROTEUS trial, aim to further evaluate the therapeutic efficacy of neoadjuvant therapy in high-risk PCa.
UNASSIGNED: NHT for high-risk PCa does not contribute to improved oncological outcome and should not be administered easily for downstaging or PSM reduction. NHT in combination with ARSI has the potential advantage of improving the oncological outcome of high-risk PCa compared to RP alone, but the results are currently unsatisfactory, and the development of individualized treatment strategies using several different therapeutic approaches is needed.

Mandibular continuity defects can result in varying degrees of cosmetic disfigurement. Restoration of form and function may require surgical reconstruction of the affected area. While surgical reconstruction may improve the overall prognostic outcomes for the patient, the definitive prosthetic phase can commence only after a substantial time lag for adequate hard/soft tissue healing. This interim phase often challenges the patient\'s masticatory ability. The traditional reconstruction of hemimandibulectomy defects has its own limitations. This case report describes the fabrication of a 3D-printed bite splint for a patient with limited mouth opening and significant malocclusion due to surgical over-correction. The prosthesis given served as an appliance to improve the masticatory ability of the patient.

UNASSIGNED: Chemotherapy and radiotherapy (RT) would induce lymphopenia, leading to a poor prognosis. This study investigated whether chemotherapy increased lymphopenia during RT and explored the impacts of different chemotherapy regimens on the lymphocyte counts of patients receiving RT.
UNASSIGNED: Clinical parameters and lymphocyte data were collected from 215 patients with locally advanced non-small cell lung cancer (LA-NSCLC). Severe lymphopenia (SRL) was defined as an absolute lymphocyte count (ALC) of ≤0.2×103 cells/μL. Patient overall survival (OS) was analyzed using the Kaplan-Meier method. The predictors of SRL were extracted using univariate and multivariate regression analyses with backward likelihood ratio elimination.
UNASSIGNED: Compared with patients without SRL, patients with SRL with LA-NSCLC showed a poorer prognosis in terms of OS (P=0.003). Of the 215 patients, 130 underwent concurrent chemoradiotherapy (CCRT) and 85 underwent sequential chemoradiotherapy (SCRT). The OS was better in patients without SRL (in the CCRT group, P=0.01 and in the SCRT group, P=0.08). The mean ALCs for CCRT and SCRT did not differ significantly (P=0.27). The minimum ALC of CCRT was significantly lower than that of SCRT (P<0.0001). CCRT was a predictor of SRL (P=0.008). However, multivariate analysis showed that the different chemotherapy regimens were not predictors of SRL (all P>0.1).
UNASSIGNED: In LA-NSCLC, the outcomes of patients with SRL were poorer than those without SRL. RT and chemotherapy were the main factors affecting SRL development, while different chemotherapy regimens were not significantly associated with lymphocyte counts in LA-NSCLC.

BACKGROUND: The outcome of hepatocellular carcinoma (HCC) is limited by its complex molecular characteristics and changeable tumor microenvironment (TME). Here we focused on elucidating the functional consequences of Maternal embryonic leucine zipper kinase (MELK) in the tumorigenesis, progression and metastasis of HCC, and exploring the effect of MELK on immune cell regulation in the TME, meanwhile clarifying the corresponding signaling networks.
METHODS: Bioinformatic analysis was used to validate the prognostic value of MELK for HCC. Murine xenograft assays and HCC lung metastasis mouse model confirmed the role of MELK in tumorigenesis and metastasis in HCC. Luciferase assays, RNA sequencing, immunopurification-mass spectrometry (IP-MS) and coimmunoprecipitation (CoIP) were applied to explore the upstream regulators, downstream essential molecules and corresponding mechanisms of MELK in HCC.
RESULTS: We confirmed MELK to be a reliable prognostic factor of HCC and identified MELK as an effective candidate in facilitating the tumorigenesis, progression, and metastasis of HCC; the effects of MELK depended on the targeted regulation of the upstream factor miR-505-3p and interaction with STAT3, which induced STAT3 phosphorylation and increased the expression of its target gene CCL2 in HCC. In addition, we confirmed that tumor cell-intrinsic MELK inhibition is beneficial in stimulating M1 macrophage polarization, hindering M2 macrophage polarization and inducing CD8 + T-cell recruitment, which are dependent on the alteration of CCL2 expression. Importantly, MELK inhibition amplified RT-related immune effects, thereby synergizing with RT to exert substantial antitumor effects. OTS167, an inhibitor of MELK, was also proven to effectively impair the growth and progression of HCC and exert a superior antitumor effect in combination with radiotherapy (RT).
CONCLUSIONS: Altogether, our findings highlight the functional role of MELK as a promising target in molecular therapy and in the combination of RT therapy to improve antitumor effect for HCC.

Despite the promise of concurrent radiotherapy (RT) and immunotherapy in head and neck cancer (HNC), multiple randomized trials of this combination have had disappointing results. To evaluate potential immunologic mechanisms of RT resistance, we compared pre-treatment HNCs that developed RT resistance to a matched cohort that achieved curative status. Gene set enrichment analysis demonstrated that a pre-treatment pro-immunogenic tumor microenvironment (TME), including type II interferon [interferon gamma (IFNγ)] and tumor necrosis factor alpha (TNFα) signaling, predicted cure while type I interferon [interferon alpha (IFNα)] enrichment was associated with an immunosuppressive TME found in tumors that went on to recur. We then used immune deconvolution of RNA sequencing datasets to evaluate immunologic cell subset enrichment. This identified M2 macrophage signaling associated with type I IFN pathway expression in RT-recurrent disease. To further dissect mechanism, we then evaluated differential gene expression between pre-treatment and RT-resistant HNCs from sampled from the same patients at the same anatomical location in the oral cavity. Here, recurrent samples exhibited upregulation of type I IFN-stimulated genes (ISGs) including members of the IFN-induced protein with tetratricopeptide repeats (IFIT) and IFN-induced transmembrane (IFITM) gene families. While several ISGs were upregulated in each recurrent cancer, IFIT2 was significantly upregulated in all recurrent tumors when compared with the matched pre-RT specimens. Based on these observations, we hypothesized sustained type I IFN signaling through ISGs, such as IFIT2, may suppress the intra-tumoral immune response thereby promoting radiation resistance.

Intraductal papillary neoplasm of the bile duct (IPNB) represents a relatively nascent pathological entity, recognized as a precancerous condition within the spectrum of cholangiocarcinoma. Surgical intervention is advocated for all patients with IPNB due to their susceptibility toward obstructive jaundice, cholangitis, and the heightened likelihood of malignant transformation. Nonetheless, the efficacy of radiation therapy for IPNB cases that are either inoperable or refractory remains inadequately substantiated. Herein, we present a case study of an IPNB patient who declined surgery, and a commendable local control was accomplished solely through the implementation of brachytherapy utilizing Ir-192. A septuagenarian Japanese man presented at our medical institution with the chief complaint of jaundice and was subsequently diagnosed with IPNB. The IPNB lesion extensively spanned from the lower intrapancreatic bile duct to the right (extending to B5/B8) and left bile ducts (up to just before B4). The patient underwent weekly endoscopic retrograde cholangiopancreatography (ERCP) sessions. The prescribed treatment regimen encompassed 36 Gy/6 Fr high-dose-rate brachytherapy (HDR-BT) administered once per week during ERCP, with each treatment session adhering to a timeframe not exceeding two hours. Two months following the initiation of treatment, a biliary endoscopy demonstrated complete resolution of the tumor lesion and amelioration of jaundice. The only observed acute adverse event was grade 2 hepatic dysfunctions. To the best of our knowledge, this represents the first documented instance of HDR-BT employed in IPNB management, suggesting its potential as a viable alternative for inoperable or refractory IPNB cases.

UNASSIGNED: This manuscript presents a bibliometric and visualization analysis of Total Body Irradiation (TBI) research, aiming to elucidate trends, gaps, and future directions in the field. This study aims to provide a comprehensive overview of the global research landscape of TBI, highlighting its key contributions, evolving trends, and potential areas for future exploration.
UNASSIGNED: The data for this study were extracted from the Web of Science Core Collection (WoSCC), encompassing articles published up to May 2023. The analysis included original studies, abstracts, and review articles focusing on TBI-related research. Bibliometric indicators such as total publications (TP), total citations (TC), and citations per publication (C/P) were utilized to assess the research output and impact. Visualization tools such as VOS Viewer were employed for thematic mapping and to illustrate international collaboration networks.
UNASSIGNED: The analysis revealed a substantial body of literature, with 7,315 articles published by 2,650 institutions involving, 13,979 authors. Full-length articles were predominant, highlighting their central role in the dissemination of TBI research. The authorship pattern indicated a diverse range of scholarly influences, with both established and emerging researchers contributing significantly. The USA led in global contributions, with significant international collaborations observed. Recent research trends have focused on refining TBI treatment techniques, investigating long-term patient effects, and advancing dosimetry and biomarker studies for radiation exposure assessments.
UNASSIGNED: TBI research exhibits a dynamic and multifaceted landscape, driven by global collaboration and innovation. It highlights the clinical challenges of TBI, such as its adverse effects and the need for tailored treatments in pediatric cases. Crucially, the study also acknowledges the fundamental science underpinning TBI, including its effects on inflammatory and apoptotic pathways, DNA damage, and the varied sensitivity of cells and tissues. This dual focus enhances our understanding of TBI, guiding future research toward innovative solutions and comprehensive care.

Germ cell tumors are malignant tumors that mostly develop in the gonads. Extragonadal localization is rare and may affect the mediastinal and sacrococcygeal regions. Mediastinal seminoma is a malignant germ cell tumor of the mediastinum. The tumor typically occurs in the anterosuperior mediastinum in males and often has a very slow growth pattern and limited potential for metastasis. And symptoms are not very characteristic, with many patients being asymptomatic and the tumor being discovered incidentally. In this paper, we report the case of a 26-year-old patient admitted for the management of a large anterosuperior mediastinal tumor encasing the vital structures of the mediastinum.

Pineal parenchymal tumors (PPTs) are rare, accounting for less than 0.3% of all primary central nervous system (CNS) tumors. Pineal parenchymal tumors of intermediate differentiation (PPTID) (WHO grade 2 or 3) show an intermediate prognosis between pineocytoma and pineoblastoma. The clinical course is unknown, and the optimal treatment for PPTID, especially for recurrence, has not been determined. We report a case of PPTID with spinal dissemination over 10 years after treatment and survival for four years. A 56-year-old woman presented with headaches and diplopia. Computerized tomography (CT) and magnetic resonance imaging (MRI) revealed a pineal mass, but leptomeningeal dissemination was not identified on whole-spine MRI. Microsurgical gross total tumor resection (GTR) was performed, and the pathological diagnosis was PPTID (grade 3). In addition, a later study found it to harbor a KBTBD4 mutation. She underwent whole-brain radiation therapy with a focal boost. The patient was unable to continue chemotherapy for severe myelosuppression after the first course of treatment. Eleven years after the surgery, she was unable to walk, and a whole-spine MRI revealed multiple masses at C3-4, T4, and cauda equina. Fluorodeoxyglucose-positron emission tomography (FDG-PET) revealed accumulations of the same lesions. No recurrence was observed in the brain. A biopsy of the caudal portion was performed, and the histopathological findings were the same as those of the initial surgery. Spinal dissemination was refractory to chemotherapy but responded to whole spine radiotherapy with focal boost, and she remained tumor-free for four years. We considered good local control with a combination of GTR and subsequent radiation therapy to contribute to long-term survival. The timing of spinal radiation administration is controversial because of the tendency for late cerebrospinal dissemination. The importance of long-term follow-up of the spine and head is emphasized. In PPTID cases with good local control, withholding spinal radiation until spinal dissemination occurs may become a long-term treatment plan.

Leptomeningeal disease (LMD) is a rare complication of advanced non-small cell lung cancer (NSCLC), associated with a poor prognosis. We report the case of a 55-year-old man, who presented with a metastatic NSCLC with limited brain and abdominal metastases. He was treated with both chemoimmunotherapy and stereotactic radiotherapy (SRT) to the brain. Despite treatment, the patient experienced progressive neurological symptoms not in keeping with the extent of disease seen on imaging of the brain. Due to this incongruence between symptoms and radiologic findings, he underwent a lumbar puncture, which had positive cytology for LMD. He had a rapid progression of symptoms and died six days after the discovery of LMD. We review the available literature regarding the prevalence of MRI-negative LMD from a solid primary malignancy.