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Meningiomas, although mostly benign, can be recurrent and fatal. World Health Organization (WHO) grading of the tumor does not always identify high-risk meningioma, and better characterizations of their aggressive biology are needed. To approach this problem, we combined 13 bulk RNA sequencing (RNA-seq) datasets to create a dimension-reduced reference landscape of 1,298 meningiomas. The clinical and genomic metadata effectively correlated with landscape regions, which led to the identification of meningioma subtypes with specific biological signatures. The time to recurrence also correlated with the map location. Further, we developed an algorithm that maps new patients onto this landscape, where the nearest neighbors predict outcome. This study highlights the utility of combining bulk transcriptomic datasets to visualize the complexity of tumor populations. Further, we provide an interactive tool for understanding the disease and predicting patient outcomes. This resource is accessible via the online tool Oncoscape, where the scientific community can explore the meningioma landscape.

Background: This systematic review aggregates the data of studies that include site‐specific analyses of patients undergoing salvage surgery for residual or recurrent hypopharyngeal squamous cell carcinoma. Methods: The primary outcomes are disease‐free, disease‐specific, and overall survival (DFS, DSS, and OS, respectively). Secondary outcomes include complications and postoperative feeding requirements. Results: Fifteen studies met the inclusion criteria with a total of 442 patients. Two‐year DFS is reported from 30.0 to 50.0% and 5‐year DFS ranges from 15.0 to 57.1%. Five‐year DSS ranges from 28.0 to 57.1%. Two‐year OS ranges from 38.8 to 52.0% and 5‐year OS ranges from 15.5 to 57.1%. Complications include pharyngocutaneous fistula (0.0–71.4%), carotid artery rupture (2.9–13.3%), and stomal stenosis (4.2–20.0%). Complete oral feeding achieved following surgery ranges from 61.9 to 100.0%, while complete gastrostomy tube dependence ranges from 0.0 to 28.6%. Conclusions: Salvage surgery for residual or recurrent hypopharyngeal squamous cell carcinoma has a relatively high complication rate and should be offered to patients with the understanding of a guarded prognosis. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusion We investigated the clinical outcomes of stereotactic body radiation therapy (SBRT) alone versus SBRT after incomplete transarterial chemoembolization (TACE) for a single recurrent hepatocellular carcinoma (HCC) smaller than 5 cm.We retrospectively reviewed the medical records of patients who underwent SBRT for a single recurrent HCC ≤5 cm, without vascular invasion or extrahepatic metastasis. Patients were divided into the SBRT‐alone group and the TACE‐SBRT group. The primary outcome was the local control (LC) rate, and secondary outcomes were survivals and treatment‐related toxicities. We additionally conducted a propensity score matching (PSM) analysis.A total of 477 patients were available for analysis. Among them, 54 patients received SBRT without prior treatment to the target lesion (SBRT‐alone group), whereas 423 patients received SBRT for viable HCC after TACE (TACE‐SBRT group). The 3‐year LC rates did not differ between the two groups (SBRT‐alone group, 88.6% vs. TACE‐SBRT group, 89.6%, P = 0.918). The 3‐year rates of overall survival, out‐of‐field intrahepatic recurrence‐free survival and recurrence‐free survival were also not significantly different (P = 0.479, 0.290 and 0.273, respectively). Even after PSM, LC and survival rates at 3 years were not significantly different.SBRT alone demonstrated comparable local control and survival outcomes to SBRT following incomplete TACE. SBRT alone may be considered an alternative treatment option for a single recurrent HCC smaller than 5 cm when curative treatments or TACE are not feasible. [ABSTRACT FROM AUTHOR]

The efficacy and safety of revision microscopic microvascular decompression (microscopic MVD) for treating residual or recurrent hemifacial spasm (HFS) remain uncertain. We conducted a systematic review and meta-analysis to evaluate the benefits and risks associated with this reoperation, focusing primarily on spasm relief, facial palsy, and hearing impairment. This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. We performed a comprehensive search of PubMed, Embase, Web of Science, and the Cochrane Library for eligible articles from their inception through June 2024. A total of 17 studies involving 719 patients were included in this meta-analysis. Among these patients, 668 experienced overall symptom relief following reoperation, resulting in a relief rate of 94% (95% CI: 92–96%). Complete relief was achieved in 603 patients, corresponding to a rate of 87% (95% CI: 80–93%). Transient facial palsy developed in 4% (95% CI: 1–8%) of patients, while persistent facial palsy was observed in 5% (95% CI: 2–8%) of patients following reoperation. Transient hearing impairment occurred in 1% (95% CI: 0–3%) of patients, while persistent hearing impairment was reported in 4% (95% CI: 1–7%) of patients. Patients with recurrent HFS have significantly lower overall and complete relief rates after reoperation compared to those with residual HFS and are at higher risk of long-term hearing loss. Our study suggests that reoperation for residual or recurrent HFS after microscopic MVD could be considered a safe and effective treatment option. Early reoperation may be indicated in specific cases, and the timing should be tailored to each patient's specific circumstances to optimize outcomes. [ABSTRACT FROM AUTHOR]

Aims: Molecular classification according to The Cancer Genome Atlas (TCGA) improves endometrial endometrioid carcinoma (EEC) prognostication and has specific treatment implications; however, original data were skewed towards low‐grade and low‐stage tumours. Herein, we molecularly classify EECs metastatic at the time of diagnosis or with subsequently documented recurrent/metastatic disease to examine correlation with clinical outcomes. Methods: TCGA categories include POLE‐mutated, microsatellite instability (MSI), p53 abnormal (p53 abnl) and no specific molecular profile (NSMP). POLE targeted sequencing at exons 9, 11, 13 and 14 and immunohistochemistry (IHC) for PMS2, MSH6 and p53 were performed to establish molecular classification. Results: The distribution in our cohort of 141 EECs was similar to that generally reported in EEC, with nine POLE‐mutated (6%), 45 MSI (32%), 16 p53 abnl (11%) and 71 NSMP (50%), with similar distributions between low‐ and high‐stage cohorts. We demonstrate that when stratified by molecular subtype, disease‐specific survival from the time of high‐stage (stages III–IV) presentation or time of recurrence in low‐stage (stages I–II) disease among metastatic and/or recurrent EEC is strongly associated with TCGA classification (high‐stage P = 0.02, low‐stage P = 0.017). Discordant molecular classification between primary and metastatic/recurrent tumours occurred in four of 105 (3.8%) patients, two related to PMS2/MSH6 IHC and two related to p53 IHC. Conclusions: We demonstrate that molecular classification is prognostically relevant not only at the time of diagnosis, but also at the time of recurrence and in the metastatic setting. Rare subclonal alterations occur and suggest a role for confirming TCGA classification in recurrent/metastatic tumours. [ABSTRACT FROM AUTHOR]

Simple Summary: This retrospective study explored the progression-free survival (PFS) of patients from Appalachian Kentucky with metastatic, persistent, or recurrent uterine cervix cancer, focusing on outcomes with various lines of chemotherapy. This study analyzed data from 127 patients treated between 2002 and 2023, examining first-, second-, and third-line treatments. After the first-line chemotherapy, the median PFS was 5.5 months. For the second- and third-line treatments, the median PFS was 5.3 and 3.0 months, respectively. Patients receiving cisplatin-containing regimens had a slightly better first-line PFS of 6.5 months. This study suggests that a five-month PFS may serve as a benchmark for future trials evaluating the efficacy of radiopharmaceuticals in this patient population. This study emphasizes the need for new treatment options, as survival outcomes tend to decrease with subsequent lines of therapy. Background: Prior preclinical studies showed promising antitumor activity and an acceptable safety profile associated with radiopharmaceuticals for patients with metastatic, persistent, or recurrent uterine cervix cancers. Whether the addition of a radiopharmaceutical to chemotherapy would significantly increase progression-free survival in such patients is untested. Our retrospective study sought to associate the line of treatment and progression-free survival as benchmarks for next-generation radiopharmaceutical development. Methods: We grouped metastatic, persistent, or recurrent uterine cervix cancer patients not amenable to curable surgery or radiotherapy between 2002 and 2023 by the line of doublet, triplet, and quadruplet chemotherapy or another intervention. After the first-line treatment, patients were monitored for radiographic progression every three months for up to three years. The primary endpoints were the first and any second or third progression-free survival intervals. Results: A total of 127 patients contributed demographic, tumor, line of treatment, and outcome data with a median follow-up of 18 months (25–75% interquartile range: 9 to 37 months). After the first-line treatment, 113 patients had local or distant progression or died from any cause, most often death from the disease (67%). Median progression-free survivals were 5.5 months (95% confidence interval: 4.8–6.0 months), 5.3 months (95% confidence interval: 4.5–6.3 months), and 3.0 months (95% confidence interval: 2.1–3.7 months) for the first-, second-, and third-line treatments, respectively. For a first-line cisplatin-containing regimen, the median progression-free survival was 6.5 months (95% confidence interval: 5.5–7.7 months). Conclusions: This study highlights the limited efficacy of current treatments for metastatic, persistent, or recurrent uterine cancer patients. A five-month progression-free survival might serve as a benchmark for the development of novel therapies in clinical efficacy trials, such as radiopharmaceuticals. [ABSTRACT FROM AUTHOR]

Background: Nonfunctioning pituitary adenomas (NFPAs) are a significant subtype of pituitary tumors, accounting for 30% of all pituitary tumors and 10–20% of intracranial tumors. The primary treatment for NFPAs is resection, but complete resection is often challenging due to the tumor's proximity to critical structures, leading to frequent recurrences. Stereotactic radiosurgery (SRS) has emerged as a viable treatment option for recurrent or residual NFPAs, but its long-term efficacy and safety profile require further investigation. Methods: This systematic review followed PRISMA guidelines and included studies published up to February 2024. We searched MEDLINE, Embase, and Cochrane databases for studies evaluating SRS for recurrent/residual NFPAs. Inclusion criteria focused on studies reporting outcomes and complications of SRS, while exclusion criteria omitted case reports, case series, and non-English studies. Data extracted included demographic details, dosimetry parameters, and follow-up durations. The risk of bias was assessed using the ROBINS-I tool, and statistical analyses were performed using single-arm meta-analyses. Results: A total of 24 studies involving 3,781 patients were included. The mean follow-up duration was 60 months. Tumor control was achieved in approximately 92.3% of patients. The risk of developing hypopituitarism post-SRS was 13.62%, while the risk for panhypopituitarism was 2.55%. New visual field deficits occurred in 3.94% of patients. Cranial nerve deficits were rare, with event rates below 1% for CN III, CN V, and CN VI. Conclusion: SRS is effective in managing recurrent or residual NFPAs, achieving high tumor control rates. However, the risk of hypopituitarism remains a significant concern, necessitating regular endocrinological monitoring. While generally safe, the potential for new visual field deficits and other cranial nerve deficits must be considered. SRS remains a valuable treatment option, but clinicians should be aware of its potential complications. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Pulmonary sequestration is uncommon congenital malformation. It is important to consider pulmonary sequestration even in young adults presenting with recurrent pneumonic symptoms because prompt surgical intervention is both feasible and curative. Moreover, in health settings lacking CT/MRI angiography service, pulmonary sequestration can be easily misdiagnosed as smear negative pulmonary tuberculosis. Therefore, strong clinical suspicion is required to prevent patient mismanagement. [ABSTRACT FROM AUTHOR]

Stargardt atrophy and geographic atrophy (GA) represent pivotal endpoints in FDA-approved clinical trials. Predicting atrophy progression is crucial for evaluating drug efficacy. Fundus autofluorescence (FAF), the standard 2D imaging modality in these trials, has limitations in patient comfort. In contrast, spectral-domain optical coherence tomography (SD-OCT), a 3D imaging modality, is more patient friendly but suffers from lower image quality. This study has two primary objectives: (1) develop an efficient predictive modeling for the generation of future FAF images and prediction of future Stargardt atrophic (as well as GA) regions and (2) develop an efficient predictive modeling with advanced 3D OCT features at ellipsoid zone (EZ) for the comparative performance in the generation of future enface EZ maps and prediction of future Stargardt atrophic regions on OCT as on FAF. To achieve these goals, we propose two deep neural networks (termed ReConNet and ReConNet-Ensemble) with recurrent learning units (long short-term memory, LSTM) integrating with a convolutional neural network (CNN) encoder–decoder architecture and concurrent learning units integrated by ensemble/multiple recurrent learning channels. The ReConNet, which incorporates LSTM connections with CNN, is developed for the first goal on longitudinal FAF. The ReConNet-Ensemble, which incorporates multiple recurrent learning channels based on enhanced EZ enface maps to capture higher-order inherent OCT EZ features, is developed for the second goal on longitudinal OCT. Using FAF images at months 0, 6, and 12 to predict atrophy at month 18, the ReConNet achieved mean (±standard deviation, SD) and median Dice coefficients of 0.895 (±0.086) and 0.922 for Stargardt atrophy and 0.864 (±0.113) and 0.893 for GA. Using SD-OCT images at months 0 and 6 to predict atrophy at month 12, the ReConNet-Ensemble achieved mean and median Dice coefficients of 0.882 (±0.101) and 0.906 for Stargardt atrophy. The prediction performance on OCT images is comparably good to that on FAF. These results underscore the potential of SD-OCT for efficient and practical assessment of atrophy progression in clinical trials and retina clinics, complementing or surpassing the widely used FAF imaging technique. [ABSTRACT FROM AUTHOR]

Background: Managing residual and recurrent craniopharyngioma effectively is crucial for improving patient outcomes. This study evaluates the combined use of gamma knife and phosphorus-32 brachytherapy, offering insights into alternative, less invasive treatment strategies. Methods: We conducted a retrospective analysis of 97 patients treated from 2010 to 2016 for residual and recurrent craniopharyngioma using gamma knife and phosphorus-32 brachytherapy. We classified these patients into three groups: superficial solid (Group A), simple cystic (Group B), and mixed cystic-solid (Group C). We assessed the treatment's effectiveness by the tumor control rates and evaluated safety by monitoring vision, endocrine function improvements, and complication rates. Results: The treatment achieved complete and adequate control rates of 49.5% and 87.6%, respectively. We observed improvements in vision or visual fields in 55.1% of the patients. The morbidity rate was 15.5%. The study found no significant differences in tumor control rates among the various lesion types. Conclusion: The combination of gamma knife and phosphorus-32 brachytherapy presents a viable, minimally invasive alternative for treating residual and recurrent craniopharyngioma. It offers high tumor control and functional improvement rates, suggesting its potential as a preferred strategy in some instances. [ABSTRACT FROM AUTHOR]

Supichaya Wangpitipanit,1 Sangduen Piyatrakul,1 Thida Tongvichean2 1Division of Community Health Nursing, Ramathibodi School of Nursing, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 2Faculty of Nursing, Shinawatra University, Pathum Thani, ThailandCorrespondence: Sangduen Piyatrakul, Division of Community Health Nursing, Ramathibodi School of Nursing, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Thung Phaya Thai, Bangkok, 10400, Thailand, Tel +66914155255, Email sangduen.tan@mahidol.ac.thBackground: The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted family caregivers of older dependents, leading to fatigue, anxiety, depression, and financial burdens, which in turn diminish their quality of life. This study investigated the integration of community participatory systems in older care to address potential COVID-19 recurrence and develop policy proposals for the integrated care of dependent older people.Methods: An explanatory sequential design was used, with stratified random sampling across six provinces, resulting in a sample of 440 family caregiver dyads and 154 full-time community stakeholders (October 2021--May 2022). Five validated tools were employed, with a content validity of 0.91 and a Cronbach’s alpha of 0.69. The data analysis included descriptive statistics and thematic analysis.Results: Among the 440 primary caregiver households, 42.73% of the older people had moderate dependence, 30.00% had severe dependence, and 27.27% had complete dependence, with common health issues, including chronic illness and comorbidities. Most older adults lived with their children/grandchildren, had insufficient income, and were informed about COVID-19 prevention measures. Family caregivers, predominantly female (average age 54), had multiple underlying conditions and provided an average of 37 hours of care per week, primarily communicating via phones or apps. The 154 stakeholders included public health volunteers and professional nurses, with an average age of 55 years, and were predominantly female (74.55%). They adhered strictly to COVID-19 precautions during their caregiving duties. This study highlights the impact of trust and COVID-19 perceptions on older care, emphasizing the need for specific forms of care, community support, and resources. Perceptions of “trust”, “stay home”, “self-care”, and “distance” significantly influenced care for dependents. The findings will inform health and social workers’ planning, operation, and training, addressing the specific care needs of dependent older adults.Conclusion: This study recommends policy interventions such as budget allocations for essential equipment, better compensation for community work, and the fostering of expertise in elder care. Emphasis is placed on fostering collaborative community agreements.Keywords: community-based care, participation, dependent older people, recurrent, outbreaks, COVID-19

The WHO (World Health Organization) conducted an elimination of cervical cancer program using triple pillar intervention strategy to target 90%-70%-90% of women before the year 2030, including (1) a full vaccination of HPV (human papillomavirus) vaccine to 90% of girls

Women with a history of spontaneous preterm birth (sPTB) face an increased risk of recurrence. Yet, the factors contributing to the increased risk are unknown, hampering the development of targeted interventions. Noninvasive quantitative ultrasound (QUS) has been validated in the characterization of cervical tissue and has the potential to provide information about postpartum cervical remodeling. The objective of this study was to determine the postpartum cervical remodeling trajectories of women over 12 mo post-delivery and to determine whether there were differences between women who delivered full-term and spontaneous preterm that were sensitive to QUS biomarkers. Data were collected prospectively from 55 women: 41 who delivered full-term and 14 who delivered spontaneously preterm at 6 wk, 3, 6, 9 and 12 mo (±2 wk) postpartum. Data from QUS biomarkers: Attenuation Coefficient; Backscatter Coefficient; Shear Wave Speed; and Lizzi–Feleppa Slope, Intercept and Midband were analyzed from the acquired radiofrequency data using a Siemens S2000 ultrasound system with a transvaginal MC 9–4 MHz probe. The biomarkers were analyzed using descriptive statistics and linear mixed-effects models. QUS biomarkers, Backscatter Coefficient and Lizzi–Feleppa Intercept showed significant differences during the year after delivery between women who had a full-term birth and sPTB (p < 0.05), suggesting that there are differences in the cervical remodeling trajectories between the two groups. All QUS biomarkers demonstrated significant variations between the full-term birth and sPTB groups over time (p < 0.05), indicating ongoing cervical remodeling for both groups during the 12-mo postpartum period. QUS biomarkers identified cervical microstructure differences and trajectories in the year after delivery between women who delivered full-term and spontaneous preterm. [ABSTRACT FROM AUTHOR]

Abstract Pituitary neuroendocrine tumors (PitNET) represent the vast majority of sellar masses. Some behave aggressively, growing rapidly and invading surrounding tissues, with high rates of recurrence and resistance to therapy. Our aim was to establish patterns of genomic, transcriptomic and methylomic evolution throughout time in primary and recurrent tumors from the same patient. Therefore, we performed transcriptome- and exome-sequencing and methylome microarrays of aggressive, primary, and recurrent PitNET from the same patient. Primary and recurrent tumors showed a similar exome profile, potentially indicating a stable genome over time. In contrast, the transcriptome of primary and recurrent PitNET was dissimilar. Gonadotroph, silent corticotroph, as well as metastatic corticotroph and a somatotroph PitNET expressed genes related to fatty acid biosynthesis and metabolism, phosphatidylinositol signaling, glycerophospholipid and phospholipase D signaling, respectively. Diacylglycerol kinase gamma (DGKG), a key enzyme in glycerophospholipid metabolism and phosphatidylinositol signaling pathways, was differentially expressed between primary and recurrent PitNET. These alterations did not seem to be regulated by DNA methylation, but rather by several transcription factors. Molecular docking showed that dasatinib, a small molecule tyrosine kinase inhibitor used in the treatment of chronic lymphocytic and acute lymphoblastic leukemia, could target DGKG. Dasatinib induced apoptosis and decreased proliferation in GH3 cells. Our data indicate that pituitary tumorigenesis could be driven by transcriptomically heterogeneous clones, and we describe alternative pharmacological therapies for aggressive and recurrent PitNET.

Abstract Background Clear cell odontogenic carcinoma (CCOC) is an odontogenic carcinoma characterized by sheets and islands of vacuolated and clear cells. The diagnosis of atypical CCOC can pose a challenge when tumor cells deviate from their characteristic clear morphology, even with the aid of genetic profiling for CCOC identification. Case presentation In this manuscript, we detailed the inaugural instance of a recurrently recurring clear cell odontogenic carcinoma (CCOC) with pronounced squamous differentiation in a 64-year-old male. The primary tumor in this individual initially displayed a biphasic clear cell phenotype. However, subsequent to the third recurrence, the clear tumor cells were entirely supplanted by epidermoid cells characterized by eosinophilic cytoplasm, vesicular chromatin, and prominent nucleoli. Notable aggressive attributes such as necrosis, conspicuous cytological malignancy, perineural dissemination, and vascular invasion were noted. Additionally, the tumor progressed to manifest lung metastases. The tumor cells exhibited positive immunoreactivity for AE1/AE3, KRT19, Pan-CK, EMA, P40, P63, CK34βE12, and P53, while they tested negative for CK35βH11, KRT7, S-100, and neuroendocrine markers. The Ki-67 proliferation index was calculated at an average of 15%. Furthermore, FISH analysis unveiled the presence of the EWSR1::ATF1 gene fusion. Conclusions This case illustrated a rare and aggressive case of CCOC characterized by significant squamous differentiation upon recurrence of the tumor.

Abstract The intricate interplay between cancer cells and their surrounding microenvironment has emerged as a critical factor driving the aggressive progression of various malignancies, including gliomas. Among the various components of this dynamic microenvironment, the extracellular matrix (ECM) holds particular significance. Gliomas, intrinsic brain tumors that originate from neuroglial progenitor cells, have the remarkable ability to actively reform the ECM, reshaping the structural and biochemical landscape to their advantage. This phenomenon underscores the adaptability and aggressiveness of gliomas, and highlights the intricate crosstalk between tumor cells and their surrounding matrix. In this review, we delve into how glioma actively regulates glioma ECM to organize a favorable microenvironment for its survival, invasion, progression and therapy resistance. By unraveling the intricacies of glioma-induced ECM remodeling, we gain valuable insights into potential therapeutic strategies aimed at disrupting this symbiotic relationship and curbing the relentless advance of gliomas within the brain. Graphical Abstract

Background and objective: With approval of novel systemic therapies within the past decade for metastatic hormone-sensitive (mHSPC) and castration-resistant (mCRPC) prostate cancer, patients may receive several therapy lines. However, the use of these treatments is under an ongoing change. We investigated contemporary treatment trends and progression-free (PFS) and overall (OS) survival of different therapy lines. Methods: Relying on our institutional tertiary-care database, we identified mHSPC and mCRPC patients. The main outcome consisted of treatment changes (estimated annual percentage change [EAPC]) within the past decade, as well as PFS and OS for different mHSPC and mCRPC treatment lines. Key findings and limitations: In 1098 metastatic patients, the median age was 70 yr with a median of two systemic therapy lines. For first-line mCRPC between 2013 and 2023, androgen deprivation monotherapy (ADT) monotherapy usage decreased significantly from 31% to 0% (EAPC −38.3%, p

Abstract Background Most gastrointestinal stromal tumors (GISTs) harbor c-KIT or PDGFRA mutations. Administration of tyrosine kinase inhibitors (TKIs) has significantly improved the survival of patients with GISTs. We aimed to evaluate the clinical outcome of advanced or recurrent GIST patients in Taiwan. Methods Patients diagnosed between 2010 and 2020 were enrolled. The collected data included baseline characteristics, treatment pattern, treatment outcome, genetic aberrations and survival status. Progression-free survival (PFS) and overall survival (OS) were analyzed and plotted with the Kaplan–Meier method. Cox regression analysis was used to analyze the prognostic factors of survival. Results A total of 224 patients with advanced or recurrent GISTs treated with TKIs were enrolled. All patients received imatinib treatment. Ninety-three and 42 patients received sunitinib and regorafenib treatment, respectively. The 48-month PFS and OS rates for patients treated with imatinib were 50.5% and 79.5%, respectively. c-KIT exon 9 and PDGFRA mutations were prognostic factors for a poor PFS and PDGFRA mutation was a prognostic factor for a poor OS in patients treated with imatinib in multivariate Cox regression analysis. The median PFS of patients who received sunitinib treatment was 12.76 months (95% confidence interval (CI), 11.01–14.52). Patients with c-KIT exon 9 mutations had a longer PFS than those with other genetic aberrations. The median PFS of patients treated with regorafenib was 7.14 months (95% CI, 3.39–10.89). Conclusions We present real-world clinical outcomes for advanced GIST patients treated with TKIs and identify mutational status as an independent prognostic factor for patient survival.

Zulfa Fidi Pranadwista,1 Wahyu Hidayat2 1Oral Medicine Residency Program, Faculty of Dentistry, Padjadjaran University, Bandung, Indonesia; 2Department of Oral Medicine, Faculty of Dentistry, Padjadjaran University, Bandung, IndonesiaCorrespondence: Zulfa Fidi Pranadwista, Oral Medicine Residency Program, Faculty of Dentistry, Padjadjaran University, Jalan Sekeloa Selatan I, Bandung, 40132, Indonesia, Tel +62 8971557962, Fax +62 22 7794121, Email zulfa21004@mail.unpad.ac.idBackground: Recurrent oral erythema multiforme (ROEM) is an uncommon subtype of erythema multiforme. Immunoglobulin E (IgE) is essential in acute allergy reactions and chronic allergic inflammatory disorders.Purpose: This report aims to describe the advantages of total IgE screening for detecting mouthwash allergic reactions associated with ROEM.Case Presentation: A 29-year-old woman came to the Oral Medicine clinic complaining of canker sores all over her mouth and swollen lips accompanied by crusts that had been bleeding easily two months prior. Complaints worsened after the patient used alcohol-containing mouthwash without a history of fever or other symptoms. Extra-oral examination showed upper and lower lip edema with hemorrhagic crusts that bleed easily. No lesions were found in other parts of the body. Intra-oral examination showed ulcers, multiple, irregular in almost the entire oral mucosa. Laboratory examination revealed non-reactive anti-HSV-1 IgG and a total IgE serum level of 612.00 IU/mL. The diagnosis based on the examination results is recurrent oral erythema multiforme.Case Management: The patient was instructed to stop using alcohol-containing mouthwash, maintain oral hygiene, a healthy lifestyle, adequate hydration, and a balanced diet. Prednisone, benzydamine HCL mouthwash, 0.025% hyaluronic acid mouthwash, multivitamins, and hydrocortisone cream were given as pharmacological therapy. The oral lesions improved in 12 days and the total IgE serum level examination showed a decrease (385 IU/mL).Conclusion: The total IgE examination can be a screening tool for mouthwash allergy-related reactions to disease and represents the response of ROEM therapy as evidenced by clinical improvement.Keywords: allergy, erythema multiforme, IgE, mouthwash, recurrent

A 56-year-old healthy woman presented with subarachnoid hemorrhage caused by ruptured vertebral artery dissecting aneurysm and was treated with internal trapping of the affected site including the aneurysm. She suffered rebleeding due to recanalization of the aneurysm 5 days after the first treatment. Because of the close proximity of the coil mass to the posterior inferior cerebellar artery (PICA) origin at first treatment, additional coil embolization by tight packing of the coil mass was planned. However, navigation of the microcatheter into the coil mass was challenging due to the tightly packed coil mass. Thus, a Marathon microcatheter, which has narrower outer diameter and is designed for liquid embolization, was used and successfully placed into the coil mass in an anterograde fashion. Thereafter, the DAC was advanced just proximal to the coil mass to reduce the kickback of the microcatheter during deployment of the coils and avoid the coil mass expansion toward the PICA origin, resulting in complete obliteration of the aneurysm with PICA preservation. Follow-up angiography performed 6 months after the second treatment showed complete obliteration of the aneurysm. The patient's course was uneventful after 1 year following the second treatment, with a modified Rankin Scale score of 1. Therefore, coil embolization through the tightly packed coil mass using a Marathon microcatheter is feasible. A low-profile DAC is also useful for enabling physicians to push the coil deployed through the flexible Marathon microcatheter.

Pituitary neuroendocrine tumors (PitNET) represent the vast majority of sellar masses. Some behave aggressively, growing rapidly and invading surrounding tissues, with high rates of recurrence and resistance to therapy. Our aim was to establish patterns of genomic, transcriptomic and methylomic evolution throughout time in primary and recurrent tumors from the same patient. Therefore, we performed transcriptome- and exome-sequencing and methylome microarrays of aggressive, primary, and recurrent PitNET from the same patient. Primary and recurrent tumors showed a similar exome profile, potentially indicating a stable genome over time. In contrast, the transcriptome of primary and recurrent PitNET was dissimilar. Gonadotroph, silent corticotroph, as well as metastatic corticotroph and a somatotroph PitNET expressed genes related to fatty acid biosynthesis and metabolism, phosphatidylinositol signaling, glycerophospholipid and phospholipase D signaling, respectively. Diacylglycerol kinase gamma (DGKG), a key enzyme in glycerophospholipid metabolism and phosphatidylinositol signaling pathways, was differentially expressed between primary and recurrent PitNET. These alterations did not seem to be regulated by DNA methylation, but rather by several transcription factors. Molecular docking showed that dasatinib, a small molecule tyrosine kinase inhibitor used in the treatment of chronic lymphocytic and acute lymphoblastic leukemia, could target DGKG. Dasatinib induced apoptosis and decreased proliferation in GH3 cells. Our data indicate that pituitary tumorigenesis could be driven by transcriptomically heterogeneous clones, and we describe alternative pharmacological therapies for aggressive and recurrent PitNET. [ABSTRACT FROM AUTHOR]

Introduction: Low grade serous ovarian carcinoma (LGSOC) is a rare subtype of ovarian cancer (OC) that is challenging to treat due to its relative chemoresistance. Given that LGSOC patients often recur in the peritoneal cavity, novel intraperitoneal (IP) chemotherapy should be explored. Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) is a method that has demonstrated peritoneal disease control in cancers with peritoneal metastases. Methods: NCT04329494 is a US multicenter phase 1 trial evaluating the safety of PIPAC in recurrent ovarian, uterine, and GI cancers with peritoneal metastases. This analysis describes the outcomes of a sub-cohort of four LGSOC patients treated with IP cisplatin 10.5 mg/m², doxorubicin 2.1 mg/m² PIPAC q4-6 weeks. Primary endpoints included dose-limiting toxicities (DLT) and incidence of adverse events (AE). Secondary endpoints were progression free survival (PFS) and treatment response based on radiographic, intraoperative, and pathological findings. Results: Four patients with LGSOC were enrolled of which three were heavily pretreated. Median prior lines of therapy was 5 (range 2-10). Three patients had extraperitoneal metastases, and two patients had baseline partial small bowel obstructive (SBO) symptoms. Median age of patients was 58 (38-68). PIPAC completion rate (=2 PIPACs) was 75%. No DLTs or Clavien-Dindo surgical complications occurred. No G4/G5 AEs were observed, and one G3 abdominal pain was reported. One patient had a partial response after 3 cycles of PIPAC and completed an additional 3 cycles with compassionate use amendment. Two patients came off study after 2 cycles due to extraperitoneal progressive disease. One patient came off study after 1 cycle due to toxicity. Median decrease in peritoneal carcinomatosis index between cycles 1 and 2 was 5.0%. Ascites decreased in 2 out of 3 patients who had =2 PIPACs. Median PFS was 4.3 months (1.7-21.6), median overall survival was 11.6 months (5.4-30.1), and objective response rate was 25%. Conclusion: PIPAC with cisplatin/doxorubicin is well tolerated in LGSOC patients without baseline SBO symptoms. IP response was seen in 2 out of 3 patients that completed =2 PIPAC cycles. Further study of PIPAC for patients with recurrent disease limited to the IP cavity and with no partial SBO symptoms should be considered. [ABSTRACT FROM AUTHOR]

Background: Clear cell odontogenic carcinoma (CCOC) is an odontogenic carcinoma characterized by sheets and islands of vacuolated and clear cells. The diagnosis of atypical CCOC can pose a challenge when tumor cells deviate from their characteristic clear morphology, even with the aid of genetic profiling for CCOC identification. Case presentation: In this manuscript, we detailed the inaugural instance of a recurrently recurring clear cell odontogenic carcinoma (CCOC) with pronounced squamous differentiation in a 64-year-old male. The primary tumor in this individual initially displayed a biphasic clear cell phenotype. However, subsequent to the third recurrence, the clear tumor cells were entirely supplanted by epidermoid cells characterized by eosinophilic cytoplasm, vesicular chromatin, and prominent nucleoli. Notable aggressive attributes such as necrosis, conspicuous cytological malignancy, perineural dissemination, and vascular invasion were noted. Additionally, the tumor progressed to manifest lung metastases. The tumor cells exhibited positive immunoreactivity for AE1/AE3, KRT19, Pan-CK, EMA, P40, P63, CK34βE12, and P53, while they tested negative for CK35βH11, KRT7, S-100, and neuroendocrine markers. The Ki-67 proliferation index was calculated at an average of 15%. Furthermore, FISH analysis unveiled the presence of the EWSR1::ATF1 gene fusion. Conclusions: This case illustrated a rare and aggressive case of CCOC characterized by significant squamous differentiation upon recurrence of the tumor. [ABSTRACT FROM AUTHOR]

Background: Radical surgery remains the primary option for locally recurrent rectal cancer (LRRC) as it has the potential to considerably extend the patient's lifespan. At present, the effectiveness of laparoscopic surgery for LRRC remains unclear. Methods: The clinical data of patients with LRRC who were admitted to the Cancer Hospital of the Chinese Academy of Medical Sciences between 2015 and 2021 were retrospectively analyzed in this study. Patients were categorized into two groups, namely the open group and the laparoscopic group, based on the surgical method used. Propensity score matching was used to reduce baseline differences. The short-term outcomes and long-term survival between the two groups were compared. Results: Curative surgery was performed on 111 patients who were diagnosed with LRRC. After propensity score matching, a total of 80 patients were included and divided into the laparoscopic group (40 patients) and the open group (40 patients). The laparoscopic group had less intraoperative bleeding (100 vs. 300, P = 0.011), a lower postoperative complication rate (20.0% vs. 42.5%, P = 0.030), a lower incidence of wound infection (0 vs. 15.0%, P = 0.026), and a shorter time to first flatus (2 vs. 3, P = 0.005). The laparoscopic group had higher 3-year overall survival (85.4% vs. 57.5%, P = 0.016) and 3-year disease-free survival (63.9% vs 36.5%, P = 0.029). Conclusions: In comparison to open surgery, laparoscopic surgery is linked to less bleeding during the operation, quicker recovery after the surgery, and a lower incidence of infections at the surgical site. Moreover, laparoscopic surgery for LRRC might yield superior long-term survival outcomes. [ABSTRACT FROM AUTHOR]

Background: Recent publications underscore the need for updated recommendations addressing less radical surgery for <2 cm tumors, induction chemotherapy, or immunotherapy for locally advanced stages of cervical cancer, as well as for the systemic therapy for recurrent or metastatic cervical cancer. Aim: To summarize the current evidence for the diagnosis, treatment, and follow-up of cervical cancer and provide evidence-based clinical practice recommendations. Methods: Developed according to AGREE II standards, the guidelines classify scientific evidence based on the Agency for Health Technology Assessment and Tariff System criteria. Recommendations are graded by evidence strength and consensus level from the development group. Key Results: (1) Early-Stage Cancer: Stromal invasion and lymphovascular space involvement (LVSI) from pretreatment biopsy identify candidates for surgery, particularly for simple hysterectomy. (2) Surgical Approach: Minimally invasive surgery is not recommended, except for T1A, LVSI-negative tumors, due to a reduction in life expectancy. (3) Locally Advanced Cancer: concurrent chemoradiation (CCRT) followed by brachytherapy (BRT) is the cornerstone treatment. Low-risk patients (fewer than two metastatic nodes or FIGO IB2-II) may consider induction chemotherapy (ICT) followed by CCRT and BRT after 7 days. High-risk patients (two or more metastatic nodes or FIGO IIIA, IIIB, and IVA) benefit from pembrolizumab with CCRT and maintenance therapy. (4) Metastatic, Persistent, and Recurrent Cancer: A PD-L1 status from pretreatment biopsy identifies candidates for Pembrolizumab with available systemic treatment, while triplet therapy (Atezolizumab/Bevacizumab/chemotherapy) becomes a PD-L1-independent option. Conclusions: These evidence-based guidelines aim to improve clinical outcomes through precise treatment strategies based on individual risk factors, predictors, and disease stages. [ABSTRACT FROM AUTHOR]

This article explores the use of cladribine (2-CdA) as a potential treatment for Rosai-Dorfman disease (RDD), a rare condition characterized by painless lymph node enlargement. The article presents case studies of adult patients with RDD who were treated with 2-CdA, showing that it can effectively reduce lymphadenopathy and improve symptoms. However, the treatment can also have severe side effects, such as bone marrow aplasia. The article suggests that 2-CdA should be reserved for patients with life-threatening or refractory RDD. [Extracted from the article]

Background: Several studies have examined return to play (RTP) and outcomes following the Latarjet procedure in contact athletes. Purpose: To investigate clinical outcomes affecting RTP following the Latarjet procedure in contact athletes. Study Design: Case series; Level of evidence, 4. Methods: A total of 67 contact athletes (72 shoulders) ≤35 years old who underwent Latarjet procedure for recurrent shoulder instability between January 1, 2018, and March 31, 2022, were retrospectively identified. Demographic information, medical history, surgical history, number of dislocations before surgery, and postoperative complications up to 6 months after surgery were reviewed. Outcomes evaluated included RTP, competition level, satisfaction, and patient-reported outcomes including visual analog scale for pain, American Shoulder and Elbow Surgeons (ASES) Score, and Disabilities of the Arm, Shoulder and Hand (DASH) scores. Results: There were a total of 67 patients (72 shoulders) included in the study with a mean age at surgery of 19.7 years for all shoulders. Of the total cohort, 46 patients (50 shoulders; [69.4%]) were available for follow-up by phone. Of the 46 patients contacted by phone, 22/46 were football players; 30/50 [60.0% of all shoulders]) were contact athletes and 19/46 [41.3%] limited contact athletes) were interviewed with a mean follow-up of 25.5 months (range, 10-49 months). Of 72 patients, 22 (30.6% of shoulders and 32.8% of patients) patients had prior shoulder surgery, most commonly arthroscopic stabilization. Only 1 patient experienced hardware failure, but this did not require reoperation. Sixteen of 46 (35%) athletes competed at the collegiate level, and 24/46 (52%) were high school athletes at the time of surgery; 34 of 46 patients (74%) returned to play, of which 30 of the 34 (88%) returned to playing at the same competition level; 15 of 22 (68%) football players returned to play. Only 4 of 51 (8%) reported subjective recurrent instability. Postoperative mean ASES score was 92.2, DASH score was 5.6, and visual analog scale for pain score was 4 (range, 0-50). A total of 43 of 46 (93%) patients reported improvement in quality of life after undergoing the Latarjet procedure for shoulder instability. Eight of 72 (11.1%) shoulders had unresolved pain or stiffness 6 months postoperatively, and 2 of 72 (2.8%) required revisions. Conclusion: Patient RTP, outcomes, and satisfaction were high following the Latarjet procedure in young contact athletes. [ABSTRACT FROM AUTHOR]

A popular approach to model interactions is to represent them as a network with nodes being the agents and the interactions being the edges. Interactions are often timestamped, which leads to having timestamped edges. Many real-world temporal networks have a recurrent or possibly cyclic behaviour. In this paper, our main interest is to model recurrent activity in such temporal networks. As a starting point we use stochastic block model, a popular choice for modelling static networks, where nodes are split into R groups. We extend the block model to temporal networks by modelling the edges with a Poisson process. We make the parameters of the process dependent on time by segmenting the time line into K segments. We require that only H ≤ K different set of parameters can be used. If H < K , then several, not necessarily consecutive, segments must share their parameters, modelling repeating behaviour. We propose two variants where a group membership of a node is fixed over the course of entire time line and group memberships are allowed to vary from segment to segment. We prove that searching for optimal groups and segmentation in both variants is NP-hard. Consequently, we split the problem into 3 subproblems where we optimize groups, model parameters, and segmentation in turn while keeping the remaining structures fixed. We propose an iterative algorithm that requires O K H m + R n + R 2 H time per iteration, where n and m are the number of nodes and edges in the network. We demonstrate experimentally that the number of required iterations is typically low, the algorithm is able to discover the ground truth from synthetic datasets, and show that certain real-world networks exhibit recurrent behaviour as the likelihood does not deteriorate when H is lowered. [ABSTRACT FROM AUTHOR]

Introduction: Recurrent ovarian cancer (ROC) presents a dismal prognosis, persistently devoid of efficacious therapeutic strategies. Over the past decade, significant shifts have transpired in ROC management, marked by the identification of novel therapeutic targets and advancements in biomarker research and innovation. Since bibliometrics is an effective method for revealing scientific literature, we conducted a bibliometric analysis of literature pertaining to ROC. Our exploration encompassed identifying emerging research trends and common patterns, analyzing collaborative networks, and anticipating future directions within this clinical context. Methods: We conducted a search in the Web of Science Core Collection (WoSCC) to acquire relevant articles as our dataset, which were then exported using R-Studio-2023.12.0-369 software. The Bibliometrix R package was utilized to perform visual analyses on countries, institutions, journals, authors, landmark articles, and keywords within this research field. Results: A total of 1538 articles and 173 reviews published between 2014 and 2023 were eventually retrieved. The annual growth rate of scientific production was 4.27%. The USA led the way in the number of published works, total citations, and collaboration. Gynecologic Oncology was the most favoured journal in this research field. Vergote I from the University Hospital Leuven, was the most influential author. At last, the most prominent keywords were "chemotherapy" (n = 124), "bevacizumab" (n = 87), and "survival" (n = 65). Clinical outcomes (prognosis, survival), chemotherapy, bevacizumab, and PARP inhibitors (olaparib, niraparib) represented the basic and transversal themes, while antibody-drug conjugate (ADC) and drug resistance were emerging themes. Cytoreduction surgical procedures and tamoxifen were niche themes, while immunotherapy and biomarkers were motor themes and had high centrality. Conclusion: The trends in the ROC research field over the past decade were revealed through bibliometric analysis. Platinum resistance, ADC, and immunotherapy have emerged as the current prominent research topics. [ABSTRACT FROM AUTHOR]

Background: Most gastrointestinal stromal tumors (GISTs) harbor c-KIT or PDGFRA mutations. Administration of tyrosine kinase inhibitors (TKIs) has significantly improved the survival of patients with GISTs. We aimed to evaluate the clinical outcome of advanced or recurrent GIST patients in Taiwan. Methods: Patients diagnosed between 2010 and 2020 were enrolled. The collected data included baseline characteristics, treatment pattern, treatment outcome, genetic aberrations and survival status. Progression-free survival (PFS) and overall survival (OS) were analyzed and plotted with the Kaplan–Meier method. Cox regression analysis was used to analyze the prognostic factors of survival. Results: A total of 224 patients with advanced or recurrent GISTs treated with TKIs were enrolled. All patients received imatinib treatment. Ninety-three and 42 patients received sunitinib and regorafenib treatment, respectively. The 48-month PFS and OS rates for patients treated with imatinib were 50.5% and 79.5%, respectively. c-KIT exon 9 and PDGFRA mutations were prognostic factors for a poor PFS and PDGFRA mutation was a prognostic factor for a poor OS in patients treated with imatinib in multivariate Cox regression analysis. The median PFS of patients who received sunitinib treatment was 12.76 months (95% confidence interval (CI), 11.01–14.52). Patients with c-KIT exon 9 mutations had a longer PFS than those with other genetic aberrations. The median PFS of patients treated with regorafenib was 7.14 months (95% CI, 3.39–10.89). Conclusions: We present real-world clinical outcomes for advanced GIST patients treated with TKIs and identify mutational status as an independent prognostic factor for patient survival. [ABSTRACT FROM AUTHOR]

Background: Adipose tissue injections, a rich source of mesenchymal stem cells, have been successfully used to promote anal fistula healing. This study aimed to investigate the efficacy of adipose tissue injection in treating patients with complex and recurrent fistulas of cryptoglandular origin. Methods: We conducted a prospective, single-center, open-label, non-randomized, interventional clinical trial from January 2020 to December 2022. We enrolled nine patients, who were evaluated after at least 12 months of follow-up. All patients had seton removal, fistula tract excision or curettage, and a mucosal flap if possible or, alternatively, an internal opening suture. We used a commercially available system to collect and process adipose tissue prior to injection. This system allowed the collection, microfragmentation, and filtration of tissue. Results: Selected cases included six men and three women with a median age of 42 (range 31–55) years. All patients had an extended disease course period, ranging from 3 to 13 (mean 6.6) years, and a history of multiple previous surgeries, including two to eight interventions (a mean of 4.4 per case). All fistulas were high transsphincteric, four cases horseshoe and two cases with secondary suprasphincteric or peri-elevator tract fistulas. Six cases (66%) achieved complete fistula healing at a mean follow-up of 18 (range 12–36) months. Three cases (33.3%) experienced reduced secretion and decreased anal discomfort. Conclusions: In patients with complex and recurrent fistulas, such as the ones described, many from palliative treatments with setons, the adjuvant injection of adipose tissue might help achieve complete healing or improvement in a significant percentage of cases. ClinicalTrials: The study protocol was prospectively registered on ClinicalTrials.gov (NCT 04750499). [ABSTRACT FROM AUTHOR]

Aim: In this study, we aimed to investigate patient characteristics, efficacy, prognostic factors, and safety of olaparib maintenance therapy for platinum‐sensitive recurrent ovarian cancer at our institution. Methods: Patients responding to platinum‐based therapy and starting olaparib maintenance therapy for recurrent epithelial ovarian, fallopian tube, or peritoneal cancer at Kurume University Hospital between January 2018 and November 2021 were enrolled in the study. Their data were extracted retrospectively from medical records. Results: In all, 50 patients were included. The median (range) age of the patients, follow‐up time, and duration of olaparib maintenance therapy were 62 (39–87) years, 21.6 (2.2–45.9) months, and 7.2 (2–45.9) months, respectively. Among the 29 patients tested for homologous recombination (HR) status, 22 (75.9%) were positive for HR deficiency (HRD), 12 (54.5%) of whom had BRCA‐positive tumors. The median progression‐free survival was 8.9 months (95% confidence interval: 6.2–12.6), and the median overall survival was 27.1 months (95% confidence interval: 22.5–40.3). Multivariate analysis of prognostic factors revealed that HRD was an independent prognostic factor for both progression‐free survival and overall survival. The most common adverse event was nausea (any grade, n = 30, 60%), resulting in drug interruption (n = 23, 46%), dose reduction (n = 17, 34%), and discontinuation of treatment (n = 1, 2%). Conclusion: Olaparib maintenance therapy for recurrent platinum‐sensitive ovarian cancer at our institution was effective, with acceptable adverse events. HRD was the most significant prognostic factor for patients with recurrent platinum‐sensitive ovarian cancer. [ABSTRACT FROM AUTHOR]

Background and Aims: Ovarian cancer maintains the highest mortality rate among gynecological malignancies. Unfortunately, two-thirds of cases are diagnosed at an advanced stage with the presence of peritoneal carcinomatosis. In this study, we aimed to present the 7-year results of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in cases where peritoneal carcinomatosis developed during the medical oncological treatment and follow-up after primary high-grade serous ovarian cancer debulking surgeries. Patients and Methods: Data from 63 patients collected prospectively in our clinic were retrospectively evaluated. Results: Postoperative Clavien–Dindo grade 3–4 complications occurred in 12 cases (19%) and 14 cases (22.2%), respectively. CD grade 3a complications developed in four cases (6.3%), which were treated with percutaneous drainage catheters, while CD grade 3b complications occurred in eight cases (12.7%), and these cases underwent reoperation. Five cases (7.9%) experienced mortality within the first 30 days. The mean survival time was determined as 44.99 months (36.33–53.65), while the median survival time was 56 months. Conclusions: In selected patients requiring redo surgery due to recurrent ovarian cancer, secondary cytoreductive surgery and hyperthermic intraperitoneal chemotherapy are associated with longer overall survival and should be considered in the treatment of advanced-stage disease. Further large-scale randomized controlled trials are needed in this regard. [ABSTRACT FROM AUTHOR]

Objectives: About 17% of patients with human papillomavirus (HPV)‐positive head and neck squamous cell carcinoma (HNSCC), which is mainly comprised of oropharyngeal SCC (OPSCC), will experience disease recurrence, which is often considered incurable when manifested at a metastatic and/or recurrent stage. We conducted a critical qualitative systematic review. Our objectives were to provide an overview of the molecular landscape of recurrent/metastatic HPV‐positive HNSCC as well as novel molecular biomarkers. Design: A literature review was conducted to identify studies reporting on the molecular characteristics of recurrent/metastatic HPV‐positive HNSCC, novel molecular biomarkers and treatment options. The reviews of abstracts, full articles, and revision of the included studies, followed by data extraction and quality assessment were performed by three independent assessors. All primary literature, such as retrospective, prospective, and clinical trials as well as basic research studies were considered, and the final search was conducted at the end of February 2023. The level of evidence was rated using the guidelines published by the Oxford Centre for Evidence‐based Medicine and quality was assessed using the Newcastle‐Ottawa Scale criteria. Results and Conclusions: The literature search resulted in the identification of 1991 articles. A total of 181 full articles were screened, and 66 articles were included in this analysis. Several studies reported that recurrent/metastatic HPV‐positive HNSCC had higher rates of TP53 mutation and were genomically similar to HPV‐negative HNSCC. The detection of circulating tumour tissue‐modified HPV DNA (ctHPVDNA) as a specific biomarker has shown promising results for monitoring treatment response and recurrence in the subset of HPV‐positive HNSCC. In addition, evidence for targeted therapy in recurrent/metastatic HPV‐positive HNSCC has emerged, including agents that inhibit overexpressed EGFR. Studies of combination immunotherapy are also underway. Our review outlines the latest evidence on the distinct molecular profiles of recurrent/metastatic HPV‐positive HNSCC as well as the clinical potential of ctHPVDNA testing in routine practice. More controlled and longitudinal studies are needed to identify additional molecular targets and to assess the performance and benefits of novel molecular biomarkers in clinical practice. [ABSTRACT FROM AUTHOR]

Phyllodes tumours or cystosarcoma phyllodes are fibroepithelial tumours of the breast and represent 1% of breast tumours. A 20-year-old nullipara presented with an enlarging left breast mass over 6 months. Although widely excised, it was reported to be a 12 × 10 × 5.5-cm borderline phyllodes tumour with involvement of the superior and inferior margins. Seven months later, she presented with a new ipsilateral breast lump measuring 8.5 × 7.5 × 4.6 cm. She underwent a left mastectomy, a three-rib resection with titanic rods for the thoracic cage reconstruction, and a latissimus dorsi flap wound closure. Histopathology revealed a high-grade malignant phyllodes tumour with features of osteoid differentiation with the nearest deep margin measuring 3 mm. She developed metastasis to the ipsilateral axillary lymph nodes and contralateral lung 2 months postoperatively. She was given palliative radiotherapy 60 Gy in 30 fractions to the left axilla. She developed sudden lower-limb weakness due to spinal metastases. The symptoms resolved with radiotherapy to the thoracic spine (T4–T8). As the lesion continued to grow rapidly from the anterior chest wall encircling towards the back, it was deemed unresectable. She was given palliative chemotherapy (doxorubicin six cycles, followed by ifosfamide one cycle) but had disease progression. She passed away 3 months later. The mainstay of treatment for phyllodes tumour is excision with a minimal margin of 1 cm. Although margins were involved after the first surgery, she was followed up as the pathology was a borderline phyllodes. When the lump recurred and had transformed, despite extensive surgery, it returned shortly and progressed. A borderline phyllodes should be excised to obtain a minimal margin of 1 cm, even if it means performing a mastectomy, to minimise recurrence. A recurrence may undergo malignant transformation which is largely chemotherapy and radiotherapy resistant. This will result in a poor outcome and decreased survival. [ABSTRACT FROM AUTHOR]

The association between persistent gram-negative bloodstream infection (GN-BSI), or ongoing positive cultures, and recurrent GN-BSI has not been investigated. Among 992 adults, persistent GN-BSI was associated with increased recurrent GN-BSI with the same bacterial species and strain (6% vs 2%; P =.04). Persistent GN-BSI may be a marker of complicated infection. [ABSTRACT FROM AUTHOR]

Background: There are limited treatment options available to improve the prognosis of patients with advanced or metastatic cholangiocarcinoma particularly intrahepatic cholangiocarcinoma (iCCA). This study aimed to evaluate the efficacy and safety of combining chemotherapy plus anti-PD-1/L1 drugs compared to chemotherapy alone in advanced, unresectable, and recurrent intrahepatic cholangiocarcinoma patients. Methods: Patients with advanced, unresectable, or recurrent iCCA who received chemotherapy combined with PD-1/PD-L1 inhibitors or chemotherapy alone were retrospectively screened and analyzed. The primary outcomes were overall survival (OS) and progression-free survival (PFS). The secondary outcomes were overall response rate (ORR), disease control rate (DCR), and safety. Results: 81 eligible patients were included in the study (chemotherapy plus anti- PD-1/L1 group n=51, and chemotherapy-alone group n=30). The median OS was 11 months for the chemotherapy plus anti-PD-1/L1 group, significantly longer than the 8 months in the chemotherapy-alone group, with a hazard ratio (HR) of 0.53 (95% CI 0.30-0.94, P = 0.008). The median PFS of 7 months in the chemotherapy plus anti-PD-1/L1 group was significantly longer than the 4 months in the chemotherapy-alone group, with HR of 0.48 (95% CI 0.27- 0.87); P = 0.002). Similarly, the combined therapy group showed a higher ORR (29.4%) and DCR (78.4%) compared to 13.3% and 73.3% in the chemotherapy-alone group, respectively. More grade 3--4 treatment-related adverse effects were recorded in the chemotherapy plus anti-PD-1/L1 group (66.7%) compared to the chemotherapy-alone group (23.3%), however, they were manageable and tolerable. Conclusion: Chemotherapy plus anti-PD-1/L1 represents a more effective and tolerable treatment option for advanced, unresectable, and recurrent iCCA patients compared to chemotherapy alone. [ABSTRACT FROM AUTHOR]

Purpose: To assess the real-world prevalence of microsatellite instability (MSI)/mismatch repair (MMR) testing and related tumor status in recurrent/advanced endometrial cancer patients in Europe. Methods: Data were from two multi-center, retrospective patient chart review studies conducted in the United Kingdom, Germany, Italy, France and Spain: The Endometrial Cancer Health Outcomes-Europe-First-Line (ECHO-EU-1L) study and the ECHO-EU-Second-Line (ECHO-EU-2L) study. ECHO-EU-1L included recurrent/advanced endometrial cancer patients who received first-line systemic therapy between 1/JUN/2016 and 31/MAR/2020 after recurrent/advanced diagnosis. ECHO-EU-2L included patients with recurrent/advanced endometrial cancer who progressed between 1/JUN/2016 and 30/JUN/2019 following prior first-line systemic therapy. Data collected included patient demographics, MSI/MMR tumor testing and results, and clinical/treatment characteristics. Results: ECHO-EU-1L included 242 first-line patients and ECHO-EU-2L included 475 s-line patients. For all patients, median age at recurrent/advanced diagnosis was 69 years, roughly half had endometrioid carcinoma histology and over 75% had Stage IIIB-IV disease at initial diagnosis. The prevalence of MSI/MMR testing in the first-line and second-line cohorts was similar (36.4 and 34.9%, respectively). Among those tested, a majority had non-MSI-high/MMR proficient tumors (80.7 and 74.7% among first- and second-line patients, respectively). About 15% had MSI-high/MMR deficient tumors in both cohorts, and a few patients had discordant results (3.4 and 10.8% among first- and second-line patients, respectively). Conclusion: Prior to the approvals of biomarker-directed therapies for recurrent/advanced endometrial cancer patients in Europe, there were low MSI/MMR testing rates for these patients of just over one-third. Given the availability of biomarker-directed therapies, increased MSI/MMR testing may help inform treatment decisions for recurrent/advanced endometrial cancer patients in Europe. [ABSTRACT FROM AUTHOR]

The treatment of head and neck cancers (HNCs) encompasses a complex paradigm involving a combination of surgery, radiotherapy, and systemic treatment. Locoregional recurrence is a common cause of treatment failure, and few patients are suitable for salvage surgery. Reirradiation with conventional radiation techniques is challenging due to normal tissue tolerance limits and the risk of significant toxicities. Stereotactic body radiotherapy (SBRT) has emerged as a highly conformal modality that offers the potential for cure while limiting the dose to surrounding tissue. There is also growing research that shows that those with oligometastatic disease can benefit from curative intent local ablative therapies such as SBRT. This review will look at published evidence regarding the use of SBRT in locoregional recurrent and oligometastatic HNCs. [ABSTRACT FROM AUTHOR]

Key Clinical Message: It is important to consider DDMS as a differential diagnosis in any patient with early childhood onset of epilepsy. Early diagnosis and optimal management are key to reducing the disabling effect of DDMS. [ABSTRACT FROM AUTHOR]

Although surgical release of upper extremity nerve compression syndromes is highly effective, persistence or recurrence of symptoms and signs may occur. Thorough investigation is necessary in this situation before treatment is recommended. If the symptoms cannot be explained by other pathology than compression of the affected nerve and if conservative management has not provided improvement, reoperation may be considered. This review provides an overview of the diagnostic and surgical considerations in the revision of carpal tunnel syndrome, cubital tunnel syndrome and thoracic outlet syndrome. Level of evidence: V [ABSTRACT FROM AUTHOR]

Chondroblastoma is a rare, benign neoplasm of chondroblast cell origin, accounting for less than 1% of primary bone tumors. It is usually diagnosed in the second decade of life with most of the cases involving the long bones such as the femur and humerus. Furthermore, over 90% of cases are in individuals under 30 years of age. In older adults, chondroblastomas are typically found in bones in the foot, such as the talus and calcaneus. Treatment is usually local curettage of the lesion with a relatively low rate of recurrence. In this case report, we present a patient with an atypical age of initial presentation at 49 years, a rare location of the chondroblastoma in the acetabulum, and a recurrence 14 years after surgical resection in the same location. The lesion's radiographic findings of intralesional calcifications alongside the high-signal, heterogeneous composition on T2-weighted MRI were supportive of the atypical diagnosis of chondroblastoma in this patient.

Key Clinical Message Pulmonary sequestration is uncommon congenital malformation. It is important to consider pulmonary sequestration even in young adults presenting with recurrent pneumonic symptoms because prompt surgical intervention is both feasible and curative. Moreover, in health settings lacking CT/MRI angiography service, pulmonary sequestration can be easily misdiagnosed as smear negative pulmonary tuberculosis. Therefore, strong clinical suspicion is required to prevent patient mismanagement.

Melioidosis is a significant health problem in tropical and subtropical regions, especially in Southeast Asia and Northern Australia. Recurrent melioidosis is a major obstacle to eliminating the disease from the community in these nations. This work aims to propose and analyze a human melioidosis model with recurrent phenomena and an optimal control model by incorporating time-dependent control functions. The basic reproduction number (R0) of the uncontrolled model is derived using the method of the next-generation matrix. Using the construction of a Lyapunov functional, we present the global asymptotic dynamics of the autonomous model in the presence of recurrent for both disease-free and endemic equilibria. The global asymptotic stability of the model’s equilibria shows the absence of a backward bifurcation for the model in both cases, whether in the absence or presence of relapse. The sensitivity analysis aims to identify the parameters that have the most significant impact on the model’s dynamics. Furthermore, qualitative analysis of the model’s global dynamics and the changing effect of the most influential parameters on R0 are supported by numerical experiments, with the results being illustrated graphically. The model with time-dependent controls is analyzed using optimal control theory to assess the impact of various intervention strategies on the spread of the epidemic. The numerical results of the optimality system are carried out using the Forward–Backward Sweep method in Matlab. We also conducted a cost-effectiveness analysis using two approaches: the average cost-effectiveness ratio and the incremental cost-effectiveness ratio.

Intussusception is the most common paediatric abdominal emergency in young children. Even though red current jelly stool is the pathognomonic feature, it only presents in less than 15% of cases. The clinical diagnosis is often missed as the presentation can mimics others. A recurrent case within 48 hours of reduction is even rare and can be falsely suspected as a normal post-reductive presentation. We highlighted a recurrence of intussusception in a 3-year-old boy, who was initially well after being discharged to home. Medical attention was sought initially but was informed that the clinical presentation could be resolved in a few days. Nevertheless, a second opinion has been sought in view of the persistent frequency pattern. Without delay, readmission of the child was arranged for surgical reduction. Regardless of the mild severity of gastrointestinal symptoms, the possibility of recurrence of intussusception should be suspected despite the presumed success of the initial intervention. [ABSTRACT FROM AUTHOR]

ObjectiveTo determine whether a non‑platinum chemotherapy doublet improves overall survival (OS) among patients with recurrent/metastatic cervical carcinoma.MethodsGynecologic Oncology Group protocol 240 is a phase 3, randomized, open-label, clinical trial that studied the efficacy of paclitaxel 175 mg/m2 plus topotecan 0.75 mg/m2 days 1-3 (n = 223) vs cisplatin 50 mg/m2 plus paclitaxel 135 or 175 mg/m2 (n = 229), in 452 patients with recurrent/metastatic cervical cancer. Each chemotherapy doublet was also studied with and without bevacizumab (15 mg/kg). Cycles were repeated every 21 days until progression, unacceptable toxicity, or complete response. The primary endpoints were OS and the frequency and severity of adverse effects. We report the final analysis of OS.ResultsAt the protocol-specified final analysis, median OS was 16.3 (cisplatin-paclitaxel backbone) and 13.8 months (topotecan-paclitaxel backbone) (HR 1.12; 95% CI, 0.91-1.38; p = 0.28). Median OS for cisplatin-paclitaxel and topotecan-paclitaxel was 15 vs 12 months, respectively (HR 1.10; 95% CI,0.82-1.48; p = 0.52), and for cisplatin-paclitaxel-bevacizumab and topotecan-paclitaxel-bevacizumab was 17.5 vs 16.2 months, respectively (HR 1.16; 95% CI, 0.86-1.56; p = 0.34). Among the 75% of patients in the study population previously exposed to platinum, median OS was 14.6 (cisplatin-paclitaxel backbone) vs 12.9 months (topotecan-paclitaxel backbone), respectively (HR 1.09; 95% CI, 0.86-1.38;p = 0.48). Post-progression survival was 7.9 (cisplatin-paclitaxel backbone) vs 8.1 months (topotecan-paclitaxel backbone) (HR 0.95; 95% CI, 0.75-1.19). Grade 4 hematologic toxicity was similar between chemotherapy backbones.ConclusionsTopotecan plus paclitaxel does not confer a survival benefit to women with recurrent/metastatic cervical cancer, even among platinum-exposed patients. Topotecan-paclitaxel should not be routinely recommended in this population. NCT00803062.

Abstract Background Ischemic stroke (IS) is one of the leading causes of death among non-communicable diseases in Thailand. Patients who have survived an IS are at an increased risk of developing recurrent IS, which can result in worse outcomes and post-stroke complications. Objectives The study aimed to investigate the incidence of recurrent IS among patients with first-ever IS during a one-year follow-up period and to determine its associated risk factors. Methods Adult patients (aged ≥ 18 years) who were hospitalized at the Stroke Center, King Chulalongkorn Memorial Hospital (KCMH) in Bangkok, Thailand, due to first-ever IS between January and December 2019 and had at least one follow-up visit during the one-year follow-up period were included in this retrospective cohort study. IS diagnosis was confirmed by neurologists and imaging. The log-rank test was used to determine the event-free survival probabilities of recurrent IS in each risk factor. Results Of 418 patients hospitalized due to first-ever IS in 2019, 366 (87.6%) were included in the analysis. During a total of 327.2 person-years of follow-up, 25 (6.8%) patients developed recurrent IS, accounting for an incidence rate of 7.7 per 100 person-year (95% confidence interval [CI] 5.2–11.3). The median (interquartile range) time of recurrence was 35 (16–73) days. None of the 47 patients with atrial fibrillation developed recurrent IS. The highest incidence rate of recurrent IS occurred within 1 month after the first episode (34 per 100 person-years) compared to other follow-up periods. Patients with small vessel occlusion and large-artery atherosclerosis (LAA) constituted the majority of patients in the recurrent IS episode (48% and 40%, respectively), with LAA exhibiting a higher recurrence rate (13.5%). Additionally, smoking status was found to be associated with an increased risk of recurrence. Conclusion The incidence rate of the recurrence was moderate in our tertiary care setting, with a decreasing trend over time after the first episode. The various subtypes of IS and smoking status can lead to differences in event-free survival probabilities.