Recurrence In Stage Research Articles

Unravelling T-cell dynamics and immune responses in initial and recurrent uveitis.

This study aimed to identify novel serological targets and investigate immune responses in patients with non-infectious uveitis, focusing on differences between initial onset and recurrent episodes. Differential gene expression analysis, immunocyte typing and T-cell receptor (TCR) gene analysis were conducted on RNA-sequenced peripheral blood samples from healthy individuals (n = 6) and non-infectious uveitis patients (n = 12), divided into 6 patients each at initial onset and recurrent stages. Peripheral blood T-cell types were analysed using flow cytometry. Bioinformatics methods included tools for RNA sequencing data processing, CIBERSORT for immune cell type prediction and specialized software for TCR repertoire analysis. Findings indicated that individuals with recurrent uveitis demonstrated a stronger adaptive immune response and a more pronounced immune imbalance compared to those with initial onset. Memory T cells were predominant in recurrent episodes, suggesting their potential role as biomarkers for disease progression. Significant differences in TCR diversity and V(D)J gene usage were observed between the various uveitis groups and healthy controls. Importantly, 38 uveitis-specific TCR sequences showed substantial expansion in the uveitis patients compared to controls. An elevated expansion of these specific TCR sequences was associated with an increased risk of uveitis development. The study highlights the critical role of adaptive immune responses and specific immune cell types in the pathogenesis of recurrent uveitis. Identification of the uveitis-specific TCR repertoire set could provide deeper insights into the disease and facilitate the development of targeted therapies for uveitis patients.

Effects of development and parental care on Hamilton's force of selection.

The force of selection describes the sensitivity of population growth to changes in life history parameters, with a focus usually on the survival probabilities from one age class to the next. Importantly, according to Hamilton the force of selection generally decreases after the onset of reproduction, thereby providing a possible explanation for patterns of senescence. A second characteristic feature is that the force of selection remains constant up to the age of first re- production. This latter observation, however, rests on the assumption that offspring become independent from their parents right after birth. I show here in a minimal model that if offspring are fully reliant on their parents, either during early embryonal development or via parental care at later stages, and during this time prevent their parents from entering a new bout of repro- duction, the force of selection on offspring survival generally increases up until the age at which offspring become independent. This provides a possible explanation for the commonly observed pattern of decreasing mortality during early ontogeny. Further, genes acting during recurrent life stages are observed to experience a heightened force of selection compared to genes that act strictly age-specifically, demonstrating the need to develop a mechanistic understanding of gene activation patterns through which to consider life history evolution.

Predicting the prognosis of patients with renal cell carcinoma based on the systemic immune inflammation index and prognostic nutritional index

The aim of the study was to analyze and discuss the value of preoperative systemic immune inflammation index (SII) and prognostic nutritional index (PNI) in predicting the prognosis of patients with renal cell carcinoma (RCC) after operation, and to establish a nomogram prediction model for patients with RCC after operation based on SII and PNI. From January 2014 to December 2018, 210 patients with RCC who underwent surgical treatment at the Xuzhou Central Hospital were selected as the research object. The receiver operating characteristic curve (ROC) was used to determine the optimal cut-off value for preoperative SII, PNI, LMR, PLR, NLR and the patients were divided into groups according to the optimal cutoff values. The survival rate of patients was evaluated. The risk factors that affect the prognosis of patients with RCC were determined by LASSO and Cox regression analysis, and a prognostic nomogram was constructed based on this result. The bootstrap method was used for internal verification of the nomogram model. The prediction efficiency and discrimination of the nomogram model were evaluated by the calibration curve and index of concordance (C-index), respectively. The average overall survival (OS) of all patients was 75.385 months, and the 1-, 2-and 3-year survival rates were 95.5%, 86.6% and 77.2%, respectively. The survival curve showed that the 5-year OS rate of low SII group was significantly higher than that of high SII group (89.0% vs. 64.5%; P < 0.05), and low PNI group was significantly lower than those in high PNI group (43.4% vs. 87.9%; p < 0.05). There were significant differences between preoperative SII and CRP, NLR, PLR, LMR, postoperative recurrence, pathological type and AJCC stage (P < 0.05). There were significant differences between preoperative PNI and BMI, platelet, NLR, PLR, LMR, postoperative recurrence, surgical mode and Fuhrman grade (P < 0.05). The ROC curve analysis showed that the AUC of PNI (AUC = 0.736) was higher than that of other inflammatory indicators, followed by the AUC of SII (0.718), and the difference in AUC area between groups was statistically significant (P < 0.05). The results from multivariate Cox regression analysis showed that SII, PNI, tumor size, tumor necrosis, surgical mode, pathological type, CRP, AJCC stage and Fuhrman grade were independent risk factors for postoperative death of patients with RCC. According to the results of Cox regression analysis, a prediction model for the prognosis of RCC patients was established, and the C-index (0.918) showed that the model had good calibration and discrimination. The subject’s operating characteristic curve indicates that the nomogram has good prediction efficiency (the AUC = 0.953). Preoperative SII and PNI, tumor size, tumor necrosis, surgical mode, pathological type, CRP, AJCC stage and Fuhrman grade are closely related to the postoperative prognosis of patients with renal cell carcinoma. The nomogram model based on SII, PNI, tumor size, tumor necrosis, surgical mode, pathological type, CRP, AJCC stage and Fuhrman grade has good accuracy, discrimination and clinical prediction efficiency.

Clinical and molecular epidemiology of malignant salivary gland tumors

Salivary gland carcinomas are a rare and heterogeneous group of malignant tumors, accounting for 3-6% of all malignant tumors in the head and neck region. The 1-, 3- and 5-year survival rates are 83%, 69% and 63% respectively. Due to new molecular pathological and genetic findings, new entities are constantly being defined as part of the recurring WHO classification of salivary gland carcinomas, so that the incidence rates of the entities are subject to constant change. The only certain risk factor for the development of salivary gland carcinomas is ionizing radiation. In addition, large tumors, cervical lymph node involvement and perineural sheath involvement significantly worsen the prognosis. Today, molecular pathology is coming to the fore, with which potential targets have been identified that can offer prognosis-improving treatment options, particularly in recurrent or distant metastatic stages. Entity-specific tyrosine kinase inhibitors such as axitinib in adenoid cystic carcinoma or larotrectinib in secretory carcinoma and cross-entity therapies such as HER2 inhibition and androgen deprivation can prolong median and progression-free survival with a favorable side effect profile.

Case report: hypertrophic osteoarthropathy improves with immune checkpoint inhibitor therapy.

We report a case of a 66 year-old male with recurrent stage IIIA non-small cell lung cancer (NSCLC) and no prior arthritis or bone disease who developed hypertrophic osteoarthropathy (HOA) prior to immunotherapy treatment. Approximately one month after the first durvalumab infusion and without other interventions for symptom management, the patient reported improvements to his hand pain, with complete resolution of symptoms after five durvalumab treatments. Repeat x-ray after nine cycles of durvalumab showed decreased periosteal thickening of the phalanges bilaterally. He had no evidence of recurrent NSCLC based on serial computed tomography one year after durvalumab initiation. To our knowledge, there are no documented reports on the isolated effect of immune-checkpoint inhibitor (ICI) therapy on HOA. This case suggests that durvalumab may have a positive role in the management of HOA in NSCLC patients. Further research is needed to better understand the interaction of ICIs, HOA and other paraneoplastic syndromes.

The economic burden of recurrence in elderly patients with completely resected, stage IIB/IIC or III melanoma: an analysis of the Surveillance, Epidemiology, and End Results-Medicare linked database

Aims To compare healthcare resource utilization (HRU) and costs between patients with or without melanoma recurrence and between patients with distant or locoregional melanoma recurrence. Methods Patients aged ≥65 years with completely resected, stage IIB/IIC or III melanoma were identified from Surveillance, Epidemiology, and End Results-Medicare data and stratified based on whether they experienced a recurrence, and whether it was distant or locoregional (separately for each stage). The index date was the date of recurrence (recurrence group) or a randomly assigned date (non-recurrence group). Patients in the recurrence and non-recurrence groups were propensity score-matched 1:1 based on patient characteristics; HRU and healthcare costs were compared between the 2 groups and between patients with distant or locoregional recurrence during the ≤24 months following index. Results After matching, 507 pairs of patients with recurrent or non-recurrent stage IIB/IIC melanoma (236 patients with distant recurrence, 271 with locoregional) and 141 pairs of patients with recurrent or non-recurrent stage III melanoma (50 patients with distant recurrence, 91 with locoregional) were included. During the first year following recurrence, unadjusted HRU was generally higher in patients with versus without recurrence and patients with distant versus locoregional recurrence among both stage IIB/IIC and III cohorts. Patients who experienced recurrence incurred $6,474 (stage IIB/IIC) or $6,112 (stage III) per patient per month (PPPM) more in unadjusted, all-cause, total healthcare costs than patients without recurrence (both p < 0.001). Patients with distant recurrence incurred $7,292 (stage IIB/IIC) or $5,436 (stage III) PPPM more in unadjusted, all-cause, total healthcare costs than patients with locoregional recurrence (both p < 0.05). Limitations Melanoma recurrence was identified using a claims-based algorithm. Conclusions Economic burden is higher in patients with versus without melanoma recurrence and patients with distant versus locoregional recurrence. There is a high unmet need for adjuvant therapies that may help to prevent or delay recurrence.

Male breast cancer: a 32-year retrospective analysis in radiation therapy referral center in northern Iran

Background: Breast cancer commonly occurs in women, and male breast cancer makes up less than 1% of all cases of breast cancer. The limited prevalence of male breast cancer has led to decreased attention being paid to this condition, resulting in its diagnosis occurring at later ages and at more severe disease stages. Objectives: This study evaluates the demographic and clinicopathological characteristics of male patients diagnosed with breast cancer who visited the northern region of Iran from 1992 to 2023. Methods: This descriptive study reviewed data from 58 cases of male breast cancer between 1992 and 2023. The study aimed to examine and describe the information connected to these patients. The data were analyzed with SPSS.22 set at P value less than 0.05. Results: The mean age of the patients examined was 62.10±13.40 years, while their mean BMI was 27.08±4.95. The study found no statistically significant correlation between BMI with stage and kinds of recurrence, including metastasis and local recurrence (P&gt;0.05). The right and left breast involvement rates were equal (48.28%) in 28 cases, and 2 cases (3.40%) had bilateral involvement. The bone was the predominant site of metastasis, accounting for 69.23% of cases. The analysis revealed no significant correlation between stage and metastasis (P=1.000) or local recurrence (P=0.543). Most metastasis and all the local recurrence were observed in stages 3 and 4. Conclusion: Male breast cancer mainly occurs in older age and is diagnosed in the advanced stages of the disease. Therefore, it is recommended to inform men and develop suitable screening programs, especially in high-risk families.

Hysterectomy versus Uterine Preservation for Pelvic organ prolapse Surgery (HUPPS): A prospective cohort study

One in five females will have surgery to treat pelvic organ prolapse in their lifetime. Uterine-preserving surgery involving suspension of the uterus is an increasingly popular alternative to the traditional use of hysterectomy with vaginal vault suspension to treat pelvic organ prolapse; however, comparative evidence with native tissue repairs remains limited in scope and quality. To compare 1-year outcomes between hysterectomy-based and uterine-preserving native tissue prolapse surgeries performed through minimally invasive approaches. We used a non-randomized design with patients self-selecting their surgical group to integrate a pragmatic, patient-centred, and autonomy-focused approach. Participants chose between uterine-preserving surgery or hysterectomy-based surgery, guided by neutral, evidence-based discussions and individualized decision-making, with support from fellowship-trained urogynecologists. Inverse probability of treatment weighting based on high-dimensional propensity scores was used to balance baseline differences across surgical groups in an effort to resemble a randomized clinical trial. A prospective cohort study of 321 participants with stage ≥2 prolapse involving the uterus who desired surgical treatment were recruited between 2020 and 2022 and followed to 1 year (retention >90%). Patients chose to receive uterine-preserving POP surgery through hysteropexy (n=151) or hysterectomy with vaginal vault suspension (n=170; reference group), with repair of anterior and/or posterior prolapse if indicated. The primary outcome was anatomic prolapse recurrence within one year, defined as apical descent ≥50% of the total vaginal length. Secondary outcomes were peri-operative, functional, clinical, and healthcare outcomes measured at 6 weeks and 1 year. Inverse probability of treatment weighted linear regression and modified Poisson regression were used to estimate adjusted mean differences (aMD) and relative risks (aRR), respectively. Apical anatomic recurrence rates at 1 year were 17.2% following hysterectomy and 7.5% following uterine-preservation, resulting in an adjusted relative risk of 0.35 (95% CI 0.15, 0.83). Uterine-preserving surgery was associated with shorter length of surgery (aMD -0.68 hours [-0.80, -0.55]) and hospitalization (aMD -4.34 hours [-7.91, -0.77]), less use of any opioids within 24 hours (aRR 0.79 [0.65, 0.97]), and fewer procedural complications (aRR 0.19 [0.04, 0.83]) than hysterectomy. Up to 1 year, uterine-preserving surgery was associated with lower risk of composite recurrence (stage ≥2 prolapse in any compartment or retreatment; aRR 0.47 [0.32, 0.69]) than hysterectomy, driven by anatomic outcomes. There were no clinically meaningful differences in functional or healthcare outcomes between surgical groups. This study adds real-world evidence to the growing body of research supportive of uterine-preserving surgery as a safe, efficient, and effective alternative to hysterectomy during native tissue prolapse repair. Given mounting evidence on safety, efficiency, and effectiveness of uterine-preserving surgery and its alignment with the preferences of approximately half of patients to keep their uterus, the standard of care should include routine offering and patient choice between uterine-preserving and hysterectomy-based surgery for pelvic organ prolapse.

Treatment Outcomes in Patients with Recurrent Adrenocortical Carcinoma.

While numerous studies have explored treatment outcomes for the overall ACC patient cohort, data on the subpopulation of patients with recurrent disease are limited. Therefore, the aim of this study was to assess treatment outcomes in patients with recurrent ACC. In this retrospective study, we included 18 patients median age 49 years (42-62); 67% female) diagnosed with recurrent ENSAT stage I-III ACC who underwent either R0 (n = 16) or Rx (n = 2) surgical resection of the tumor. The median time from the initial surgery to ACC recurrence was 29 months (IQR 18-50). Seven patients (39%) manifested local recurrence, while 11 patients (61%) developed distant metastases. The median follow-up duration after tumor recurrence was 32 months (IQR 25-53). Regarding the treatment of ACC recurrence, 10 patients underwent a second surgery either as an alone procedure (n = 4), or in combination with mitotane (n = 4), mitotane and chemotherapy (n = 1), or mitotane combined with radiotherapy (n = 1). The remaining patients received treatment involving chemotherapy±mitotane (n = 4) and locoregional therapy ±chemotherapy (n = 3). One patient chose not to proceed with further management and follow-up. The median PFS was 17 (95% CI 8-26) months while the median OS was not reached. In the multivariate model, increased mortality was associated with advanced age (p = 0.04) and a shorter interval to ACC recurrence (p = 0.03). A significant proportion of patients with ACC recurrence experience disease progression or second recurrence, despite all treatment efforts. Nevertheless, by integrating diverse treatment modalities, many patients have the potential to attain long-term survival.

Importance of mediastinal granulomatous/sarcoid-like lymphadenopathy in extrathoracic malignancies.

In patients with extrathoracic malignancies (ETM), granulomatous lymph adenopathy called sarcoid-like reactions (SLR) can be seen in the regional or draining lymph nodes. We hypothesized that SLR may be a sign of imminent metastasis and investigated the clinical course and rate of recurrence in patients with ETM and granulomatous mediastinal lymphadenopathy (MLN). In this retrospective observational study, we reviewed the medical files of patients with known ETM and who underwent EBUS-TBNA for initial staging or detection of recurrence from 2011 to 2023. Patients with granulomatous MLN were included. Forty-one patients (29 female) enrolled in the study. Breast and colorectal carcinomas were the most common malignancies. A total of 81 lymph nodes were sampled. The final diagnosis of patients was five sarcoidosis, one tuberculosis, one second primary, one drug reaction, and 33 SLR. Among patients with SLR, in one patient lymph nodes progressed during the follow-up and were accepted as false-negative without confirmatory biopsy. The negative predictive value (NPV) of granulomatous MLN for metastasis was 97.05%. Granulomatous MLN may be due to tuberculosis, drug reaction, sarcoidosis, or SLR in patients with ETM. SLR has a high NPV in patients with ETM. Follow-up imaging rather than confirmatory biopsy is reasonable in these patients.

Increased CCT5 expression is a potential unfavourable factor promoting the growth of nasopharyngeal carcinoma.

Chaperonin containing TCP1 subunit 5 (CCT5) encodes the CCT5 protein subunit of chaperonin-containing TCP-1 (CCT/TRiC) complex, and is shown to be upregulated in tumour pathogenesis. The study aim was to investigate the differential expression of CCT5 between nasopharyngeal carcinoma (NPC) and noncancerous nasopharyngeal tissues, and the correlation between CCT5 expression and clinicopathological parameters/prognosis in patients with NPC. Microarray assay data were evaluated for differential expression between NPC and noncancerous nasopharyngeal tissues. CCT5 expression in NPC and noncancerous nasopharyngeal tissues was determined at mRNA and protein levels by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry. Relationships between CCT5 expression in NPC, clinical parameters, and prognosis were statistically analysed. CCT5-mediated cell proliferation was assessed using EdU and cell counting kit-8. Western blot and co-immunoprecipitation were utilized to explore E3 ubiquitin-protein ligase parkin (PARK2)-induced degradation of CCT5. Microarray data showed CCT5 levels to be significantly increased in NPC versus noncancerous nasopharyngeal tissues, which was confirmed by qRT-PCR and immunohistochemical assays. Increased CCT5 protein levels positively correlated with tumour size, tumour recurrence, and clinical stage, and inversely correlated with patient's overall survival. Multivariate Cox regression analysis showed that enhanced CCT5 protein expression is an independent prognostic factor for patients with NPC. Overexpression of CCT5 markedly induced NPC cell proliferation. Finally, PARK2, as a suppressive E3 ubiquitin-ligase enzyme, was shown to bind CCT5 and induce degradation in NPC. Increased CCT5 may be an unfavourable factor promoting NPC growth. Binding of PARK2 to CCT5 was associated with CCT5 degradation, suggesting that PARK2 is an upstream negative modulator in NPC.

Comprehensive genomic profiling in multiple cancer types: A comparative analysis of the National Biobank Consortium of Taiwan and clinical practice cohorts

BackgroundThis retrospective study analyzed tumor tissue profiling data to assess the potential of comprehensive genomic profiling (CGP) for patient care across diverse solid tumors. Material and methodsPatients with newly diagnosed or recurrent stage IIIB or IV lung adenocarcinoma with a null immunophenotype and esophageal, gastric, pancreatic, or bile duct cancer between January 2020 and July 2023 at two medical centers in Taiwan were included. One cohort was a part of the National Biobank Consortium of Taiwan project, whereas the other consisted of patients undergoing routine clinical practice. Tumor samples were subjected to CGP using FoundationOne®CDx, with therapeutic implications determined using OncoKB classification. ResultsFoundationOne®CDx testing of 574 patients was successful in 456 (79.4%) patients. Clinically actionable genomic alterations were detected in 21.1% (96/456) of the patients, including 17.5%, 2.9%, and 0.7% of patients with evidence levels 1, 2, and 3, respectively. Lung adenocarcinoma accounted for the largest proportion of samples with at least one actionable gene alteration (63.2%), followed by bile duct (26.9%), gastric (17.6%), esophageal (4.0%), and pancreatic (3.1%) cancers. Based on CGP results, 43 patients (9.4%) received matched targeted therapy. The median overall survival of patients who received matched therapy or not was 26.1 months (95% confidence interval (CI), 16.7–35.5 months) and 10.6 months (95% CI, 8.1–13.1 months; hazard ratio, 0.28, 95% CI, 0.14–0.55, p < 0.001), respectively. ConclusionsThis study provides comprehensive insights into the genomic profiles of diverse cancers in Taiwan, highlighting the crucial role of CGP in identifying actionable genomic alterations and guiding effective therapeutic strategies in real-world practice.

Sulindac exhibits anti-proliferative and anti-invasive effects in uterine serous carcinoma cells

PurposeUterine serous carcinoma (USC) is a highly aggressive and frequently recurring subtype of endometrial cancer with limited treatment options for advanced or recurrent stages. Sulindac, a classic non-steroidal anti-inflammatory drug, has demonstrated anti-tumor activity in several pre-clinical tumor models. This study aims to evaluate the effect of sulindac on cell proliferation and invasion in USC cells.MethodsHuman USC cell lines ARK-1 and SPEC2 were treated with different concentrations of sulindac. Cell proliferation was assessed using MTT and colony formation assays. ELISA assays measured cellular stress, cleaved caspase 3 activity, antioxidant ability, and adhesion. Cell cycle arrest was evaluated by Cellometer. The invasive capability was detected by wound healing assay. Western blotting was used to analyze the changes in protein expression induced by sulindac.ResultsExposure to sulindac decreased cellular viability in a dose-dependent manner in ARK-1 and SPEC2 cells. Sulindac effectively inhibited cell cycle progression, increased cellular stress, caused apoptosis, and reduced cell adhesion and invasion in USC cells. Additionally, sulindac decreased the expression of COX-2 and blocked phosphorylation of NF-κB induced by TNF-α.ConclusionSulindac is a potential therapeutic agent for USC that deserves further exploration in pre-clinical studies and potentially future clinical trials.

Periprosthetic joint infection in patients with rheumatoid arthritis: case series

Introduction The differential diagnosis of periprosthetic joint infection (PJI) is challenging in patients with systemic diseases due to identical clinical and laboratory patterns and activity of the inflammatory process.The objective was to evaluate the diagnostic data and results of debridement of PJI in patients with rheumatoid arthritis using a case series.Material and methods A retrospective analysis of surgical treatment of PJI was produced in patients with rheumatoid arthritis between 2014 and 2022. PJI was verified based on ICM criteria. A poor outcome included the presence of clinical and laboratory signs of infection on admission to the second stage of treatment and recurrence after successful debridement.Results Among the 524 cases of PJI, 35 (6.7 %) were patients with rheumatoid arthritis with 48.6 % receiving antibiotics prior to admission. Culture-negative infection was recorded in 38.4 %. PJI was not confirmed in five cases (14.3 %). High average values of inflammatory markers were registered in the blood (ESR, CRP and D-dimer) before and after debridement; decreased ESR and leukocyte count in the synovial fluid was statistically significant. Favorable outcomes were obtained in 82.9 % of cases at mid term with every fifth patient treated with a spacer or arthrodesis.Discussion The incidence of culture-negative infection in patients with systemic diseases was reported as much as 27–37 %. A systematic review of the literature showed that the percentage of band neutrophils in synovial fluid has a sensitivity of 95.2 % and a specificity of 85.0 %, with an optimal threshold of 78 % sufficient to verify infection. The poor outcomes we identified resulted from two- or three-stage surgical treatment. Other authors reported better outcomes with two-stage debridement.Conclusion Culture-negative infection was common in cases of PJI observed in patients with rheumatoid arthritis. Favorable outcomes were seen mostly with two-stage surgical treatment. Inflammatory markers ESR, CRP and D-dimer did not reach normal values during diagnosis and treatment of infection indicating the inapplicability of standard diagnostic criteria for PJI in patients with rheumatoid arthritis.

Indications for nuclear medicine imaging in prostate cancer

Nuclear medicine imaging for prostate cancer has advanced significantly over the past decade. A survey is presented in this review. PSMA-PET/CT is a new highly accurate method that has been introduced, but bone scans and bone-PET continue to be widely applied. PSMA-PET/CT still lacks sufficient patient outcome data to be recommended for treatment allocation when used for primary staging. However, the literature and clinical guidelines support its use at the stage of biochemical recurrence. In Denmark, the use of nuclear medicine examinations for prostate cancer aligns with clinical guideline recommendations.

Real-world insights from comprehensive genomic profiling across multiple cancer types.

106 Background: This retrospective study was conducted to analyze tumor tissue profiling data to assess the potential of applying comprehensive genomic profiling (CGP) in patient care across diverse solid tumors. Methods: Patients with newly diagnosed or recurrent stage IIIB or IV lung adenocarcinoma with the null immunophenotype, esophageal, gastric, pancreatic, or bile duct cancer between January 2020 and July 2023 at two medical centers in Taiwan were included in the National Biobank Consortium of Taiwan project. The tumor samples were subjected to CGP using FoundationOneCDx, with therapeutic implications determined using OncoKB classification. Results: FoundationOneCDx testing of 574 patients was successful in 456 (79.4%) patients. Clinically actionable genomic alterations were detected in 21.1% (96/456) of the patients, including 17.5%, 2.9%, and 0.7% of patients at evidence levels 1, 2, and 3, respectively. Lung adenocarcinoma accounted for the largest proportion of samples with at least one actionable gene alteration (63.2%), followed by bile duct (26.9%), gastric (17.6%), esophageal (4.0%), and pancreatic (3.1%) cancer. Based on the CGP results, 43 patients (9.4%) received matched targeted therapy. The median overall survival of patients who received matched therapy or not was 26.1 months (95% confidence interval (CI), 16.7–35.5 months) and 10.6 months (95% CI, 8.1–13.1 months; hazard ratio, 0.28, 95% CI, 0.14–0.55, p &lt; 0.001), respectively. Conclusions: This study provides comprehensive insights into genomic profiling across diverse cancers in Taiwan, highlighting the crucial role of CGP in identifying actionable genomic alterations and guiding effective therapeutic strategies in real-world practice.

Prevalence and associated factors of post-traumatic stress symptoms in hospitalised children with cancer and their parents in South China: A multicentred cross-sectional study

ObjectiveThis study aimed to examine the prevalence and risk factors of Post-Traumatic Stress Symptoms (PTSS) in hospitalised children with cancer and their parents and explore the PTSS correlation between parents and children. MethodsData were collected using the University of California at Los Angeles (UCLA) Posttraumatic Stress Disorder-Reaction Index for DSM-IV and the Chinese version of the Impact of Event Scale-Revised Questionnaire. ResultsOut of 203 families with hospitalised children with cancer, 77.3% of parents and 7.9% of children experienced PTSS. Time since diagnosis of less than 3 months (β = −0.063, P < 0.001), actively seeking financial help (β = −0.190, P = 0.031), children living in rural areas (β = 0.166, P = 0.023) and having a daughter with cancer (β = 0.135, P = 0.040) were risk factors for parental PTSS. At the early stages of diagnosis (β = 0.118, P = 0.017), recurrence (β = 0.140, P = 0.042) and low monthly household income (β = −0.283, P = 0.003) were risk factors for children's PTSS. No significant correlation between parental PTSS and children's PTSS (r = −0.06, P > 0.05). ConclusionsThe hospitalised children with cancer had a low prevalence of PTSS, but their parents' PTSS prevalence was high. No significant correlation was observed between parental and children's PTSS. Attention should be given to the mental health of families with hospitalised children with cancer. Early psychosocial support should be provided, especially to families with poor economic situations and a newly diagnosed or relapsed child.

Establishment and characterization of a novel MDM2/MYCN-co-amplified neuroblastoma cell line, NBN-SHIM, established from a late recurrent stage MS tumor.

The biological heterogeneity of neuroblastoma underscores the need for an in vitro model of each molecularly defined subgroup to investigate tumorigenesis and develop targeted therapies. We have established a permanently growing cell line from a 12-year-old girl who developed a late recurrent stage MS, MDM2-amplified neuroblastoma arising in the liver and performed histological, molecular, cytogenetic, exome, and telomere analyses of the recurrent tumor and the cell line. On histology, the recurrent tumor was immunoreactive for TP53, CDKN1A, and MDM2. A molecular cytogenetic study of the recurrent tumor revealed the amplification of MDM2 but no amplification of MYCN. The established cell line, NBM-SHIM, showed amplification of both MDM2 and MYCN on double-minute chromosomes. A copy number evaluation based on exome data confirmed the finding for MYCN and MDM2 and further identified high ploidy on CDK4 and GLI2 loci in the recurrent tumor and the cell line. The telomere maintenance mechanism on the cell line is unusual in terms of the low expression of TERT despite MYCN amplification and alternative lengthening of telomeres suggested by positive value for C-circle assay and telomere contents quantitative assay. The cell line is unique because it was established from a MYCN-nonamplified, MDM2-amplified, late-relapsed stage MS neuroblastoma, and MYCN amplification was acquired during cell culture. Therefore, the cell line is a valuable tool for investigating neuroblastoma tumorigenesis and new molecular targeted therapies for disrupted ARF-TP53-MDM2 pathway and amplification of MDM2 and CDK4.

Boron neutron capture therapy as a larynx-preserving treatment for locally recurrent laryngeal carcinoma after conventional radiation therapy: A preliminary report

ObjectiveLaryngeal preservation and a radical cure are the treatment goals for laryngeal carcinoma, and larynx-preserving therapy is generally preferred for early-stage laryngeal carcinoma. When laryngeal carcinoma recurs locally, patients are often forced to undergo total laryngectomy, resulting in loss of vocal function. However, many patients with laryngeal carcinoma who have residual or recurrent disease after radiotherapy wish to preserve their voice. The purpose of this study was to investigate the possibility of using BNCT as a larynx-preserving treatment for residual or recurrent laryngeal carcinomas following radical irradiation. Patients and MethodsThis study included 15 patients who underwent BNCT for residual or recurrent laryngeal carcinoma after radical laryngeal carcinoma irradiation. The number of treatment sessions for all patients was one irradiation. Before BNCT, the recurrent laryngeal carcinoma stage was rT1aN0, rT2N0, rT2N1, rT3N0, rT3N1, and rT4aN0 in one, six, one, three, one, and three patients, respectively. The median maximum tumor diameter before BNCT was 15 mm (8–22 mm). All patients underwent a tracheostomy before BNCT to mitigate the risk of upper airway stenosis due to laryngeal edema after BNCT. Treatment efficacy was evaluated retrospectively using monthly laryngoscopy after BNCT and contrast-enhanced CT scans at 3 months. The safety of treatment was evaluated based on examination findings and interviews with patients. ResultsThe median hospital stay after BNCT was 2 days (1–6). The response rate at three months after BNCT in 15 patients with locally recurrent laryngeal carcinoma was 93.3 %, and the CR rate was 73.3 %. The most frequent adverse event associated with BNCT was laryngeal edema, which occurred in nine patients the day after BNCT. The average course of laryngeal edema peaked on the second day after BNCT and almost recovered after 1 week in all patients. One patient had bilateral vocal fold movement disorders. None had dyspnea because of prophylactic tracheostomy. No grade four or higher adverse events occurred. Other grade 2 adverse events included pharyngeal mucositis, diarrhea, and sore throat. Three months after BNCT, tracheostomy tubes were removed in nine patients, retinal cannulas were placed in three patients, and voice cannulas were placed in three patients. ConclusionsBNCT for locally recurrent laryngeal carcinoma can safely deliver radical irradiation to tumor tissues, even in patients undergoing radical irradiation. BNCT has shown antitumor effects against recurrent laryngeal carcinoma. However, further long-term observations of the treatment outcomes are required.

Identifying key pathogenic mechanisms and potential intervention targets for recurrence after laryngeal cancer treatment through bioinformatics screening.

Laryngeal cancer (LC), a prevalent malignant tumor of the head and neck, is characterized by a high rate of postoperative recurrence and significant treatment challenges upon recurrence, severely impacting patients' quality of life. There is a pressing need for effective biomarkers in clinical practice to predict the risk of LC recurrence and guide the development of personalized treatment plans. This study uses bioinformatics methods to explore potential biomarkers for LC recurrence, focusing on key genes and exploring their functions and mechanisms of action in LC recurrence. The aim is to provide new perspectives and evidence for clinical diagnosis, prognostic evaluation, and targeted treatment of LC. Gene expression profiles from the GSE25727 data set in the Gene Expression Omnibus database were analyzed to detect the differentially expressed genes (DEGs) between the tumor tissues of postoperative recurrent and non-recurrent early stage LC patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were also conducted. A protein-protein interaction (PPI) network and transcription factor (TF)-DEG-microRNA (miRNA) network were developed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, with key genes selected using the Molecular Complex Detection (MCODE) plugin. A Gene Set Enrichment Analysis (GSEA) was carried out to investigate the possible mechanisms of the key genes. A retrospective analysis was conducted using the clinical data of 83 LC patients. Immunohistochemical staining was used to examine the transcription level of the key genes in the LC tumor tissues and the factors affecting postoperative recurrence. A total of 248 upregulated and 34 downregulated DEGs were identified in the GSE25727 data set. The PPI network analysis identified a significant module and five candidate genes (i.e., RRAGA, SLC38A9, WDR24, ATP6V1B1, and LAMTOR3). The construction of the TF-DEG-miRNA network indicated that ATP6V1B1 might be regulated by one TF and interact with 17 miRNAs. The KEGG and GSEA analyses suggested that ATP6V1B1 may influence LC recurrence through the involvement of pro-inflammatory and pro-fibrotic mediators, glutathione metabolism, matrix metalloproteinases, immune regulation, and lymphocyte interactions. The recurrence rate of the 83 LC patients included in the study was 19.3% (16/83). The immunohistochemistry results indicated that ATP6V1B1 was highly expressed in patients with recurrent LC. The univariate and multivariate logistic regression analyses revealed that tumor stage T3 (P=0.04), tumor stage T4 (P=0.01), and a high expression of ATP6V1B1 (P=0.02) were risk factors for recurrence after surgical treatment in LC patients. The key genes and signaling pathways identified through the bioinformatics screening provide insights into the potential mechanisms of the pathogenesis of LC. ATP6V1B1 may promote the recurrence of LC by weakening the immune phenotype. Our findings provide a theoretical basis for further research into clinical diagnostics and treatment strategies for LC.