Primary Malignancy Research Articles

Mitochondrial Iron Metabolism as a Potential Key Mediator of PD-L1 Thermal Regulation

Glioblastoma (GBM) is the most common primary brain malignancy in the U.S. with a 5-year overall survival < 5% despite an aggressive standard of care. Laser interstitial thermal therapy (LITT) is a surgical approach to treating GBM that has gained traction, providing a safe option for reducing intracranial tumor burden. LITT is believed to potentially modulate GBM immune responses; however, the biochemical mechanisms underlying the modulation of immune checkpoints in GBM cells have been poorly characterized. The present study aimed to preliminarily evaluate the effects of thermal therapy and radiation on PD-L1 modulation in vitro, as a function of IDH mutational status. U87 cells and their IDH-mutant counterpart (U87R132H), which was generated using a crispr-cas9 knock-in approach, were utilized for this preliminary evaluation. Cell heating was achieved by harvesting with trypsin centrifugation where the cell pellets were treated on a heat block for the associated time and temperature. Following thermal therapy, cells were resuspended and irradiated using a 37-Cesium irradiator at 0.6 Gy min−1. Immediately following treatment, cells were either plated as single cells to allow colonies to form, and stained with Coomassie blue to be counted approximately 10–14 days later or harvested for Western blot analysis. Cell lysates were analyzed for PD-L1 expression with respect to various iron metabolic parameters (mortalin (HSPA9), transferrin receptor, and ferritin heavy chain) using a Western blotting approach. In both U87 and U87R132H cell lines, thermal therapy showed a temperature-dependent cell-killing effect, but U87R132H cells appeared more sensitive to thermal treatment when treated at 43 °C for 10 min. Moreover, thermal therapy had minimal effects on cell responses to 2 Gy irradiation. Treatment with thermal therapy downregulated PD-L1 expression in U87R132H cells, which was associated with increased expression of the mitochondrial iron metabolic enzyme, HSPA9. Thermal therapy reversed the radiation-induced overexpression of PD-L1, transferrin receptor, and ferritin heavy chain in U87R132H cells. No effects were observed in wild-type U87 cells. Moreover, Ga(NO3)3 depleted mitochondrial iron content which, in turn, significantly enhanced the sensitivity of U87R132H cells to thermal therapy and 2 Gy irradiation and caused a significant increase in PD-L1 expression. These results suggest that thermal therapy alone can modulate the immune checkpoint PD-L1. This effect was more pronounced when thermal therapy was combined with radiation. Mechanistically, mitochondrial iron trafficking through HSPA9 may coordinate the regulation of PD-L1 in the context of thermal therapy and ionizing radiation, which can be targeted with gallium-based therapy. These novel, preliminary findings warrant further mechanistic investigations in pre-clinical models of LITT.

Prognosis and clinicopathological features of patients with early-onset and late-onset colorectal cancer with second primary malignancies.

The risk of developing a second primary malignancy differs among colorectal cancer patients in different age groups. This study aimed to investigate the differences in prognosis and clinicopathological features of patients with early-onset colorectal cancer and late-onset colorectal cancer who developed second primary malignancies. The study included 15489 patients who underwent surgery for colorectal cancer at Fudan University Shanghai Cancer Center between January 2008 and December 2018. Data pertaining to these patients were derived from the database. A total of 680 (4.5%) patients subsequently developed a second primary malignancy. Considering death as a competing event, the 10-year cumulative risk of second primary malignancy for early-onset colorectal cancer was 5.3%, compared with 7.3% for late-onset colorectal cancer. Cox analysis showed that late-onset colorectal cancer, colon cancer, smaller tumor size, and fewer tumor nodules without residual lymph node structure, chemotherapy, and radiotherapy were independent risk factors for second primary malignancy. In our patient cohort, early-onset colorectal cancer was associated with better prognosis compared to late-onset colorectal cancer, for both overall survival and second primary malignancy-free survival. In addition, there was insufficient evidence that early-onset colorectal cancer also affected prognosis after the occurrence of second primary malignancies. The risk of early-onset colorectal cancer subsequently developing second primary malignancy was significantly lower than late-onset colorectal cancer, and the second primary malignancies of early-onset colorectal cancer were more likely to be colorectal cancer. Overall survival and second primary malignancy-free survival of early-onset colorectal cancer were consistently better than late-onset colorectal cancer.

Practical approach to diagnose and manage benign liver masses.

Benign liver lesions are among the most commonly diagnosed abnormalities in liver imaging. They are often discovered incidentally during routine examinations or imaging conducted for unrelated reasons. These can be solid lesions, such as hemangiomas, focal nodular hyperplasia, hepatic adenomas, or cystic lesions. Recent advancements in MRI technology, particularly with hepatocyte-specific contrast agents, have enhanced the characterization of these lesions, reducing the reliance on invasive tissue sampling. Nevertheless, tissue sampling retains a crucial role in the evaluation of indeterminate lesions or those with malignant potential. While most benign liver lesions are asymptomatic, some can become symptomatic, causing discomfort, pain, or bleeding, particularly if the lesion is large. A deep understanding of the molecular underpinnings of the lesions is crucial for tailoring patient management strategies, particularly in distinguishing lesions that require surgical intervention from those that can be monitored. For instance, the molecular subclassification of hepatic adenomas has provided mechanistic insights and identified certain subtypes that are at higher risk of malignancy. Most benign liver lesions can be safely monitored; however, in patients with cirrhosis or a known primary malignancy, a high index of suspicion for cancer is required. It is crucial to carefully evaluate any liver lesion identified in these patients to ensure that indeterminate lesions are not overlooked. Effective management of benign liver lesions involves a multidisciplinary team, including hepatologists, surgeons, and radiologists, ensuring a comprehensive and individualized approach to patient care. This review outlines the clinical presentation of common benign liver lesions, providing a diagnostic and management framework. Emphasis is placed on a personalized approach to minimize patient distress and optimize outcomes by leveraging imaging advancements and multidisciplinary collaboration.

OA26 Atypical Multisystem Inflammation related to infection or just plain old polyarteritis nodosa?

Abstract Introduction We present the case of a 5-year-old boy with episodes of pyrexia of unknown origin associated with polyarthritis, central neuroinflammation and mucocutaneous manifestations. His skin biopsy demonstrated a nodular vasculitis which could be consistent with polyarteritis nodosa. Interestingly though, he had additional atypical rashes, ocular inflammation and evidence of acute and past streptococcal infection and his fever and CRP normalised prior to corticosteroid initiation. Case description A five-year-old British African male presented with five-week history of persistent fever, headaches, joint pain and bilateral eye pain. He was transferred to a tertiary paediatric infectious disease’s unit due to unrelenting fever with no fixed pattern, despite nine days of broad-spectrum intravenous antibiotics. He was diagnosed with neuroinflammation of uncertain aetiology, evidenced by leptomeningeal enhancement and bilateral papillitis on brain MRI. CSF microbiology and autoimmune profiles were negative. There was no evidence of primary malignancy. The fever resolved with pulsed IV methylprednisolone and the child was discharged home on a weaning regime of oral prednisolone. After stopping steroid treatment, he represented with high-grade fever, limping, anterior uveitis and new-onset non tender cutaneous lesions, plaques over eyelids and cheek and annular lesions over arms, legs and buttocks. Repeat MRI of the brain and spine showed resolution of previous neuroinflammation. Blood tests revealed raised ANA, IgG and ASOT titre, and his throat swab was positive for Group A Streptococcus. He completed 10 days of intravenous antibiotics and oral high dose ibuprofen (10 mg/kg TDS). On review by tertiary paediatric rheumatology, he was identified to have pleomorphic skin rash and subcutaneous nodules. Skin and deep tissue biopsy confirmed lobular and septal panniculitis with necrotising vasculitis, consistent with a nodular vasculitis. Treatment with high-dose steroid and mycophenolate mofetil (MMF) was initiated, but his CRP and fever had resolved prior to his first dose. He experienced improvement in systemic symptoms and arthritis; however, skin lesions persisted, with appearance of new lesions and hyperpigmentation, on reduction of steroid dose. His course was complicated by acute varicella infection, requiring oral aciclovir. Further treatment trials included topical tacrolimus and topical corticosteroids for his skin lesions. At one biopsy site, he experienced significant delay in wound healing. The genetic panel for primary immunodeficiency panel (R15) demonstrated no pathological variants. Discussion This case report highlights that, whilst the biopsy may be consistent with nodular vasculitis, such as PAN, the clinical manifestations are not perfectly aligned. Discussion within the rheumatology community would support optimal patient care. Childhood-onset Polyarteritis Nodosa (c-PAN) is a rare systemic vasculitis. Although the aetiology is unknown, associations with infections like group A streptococcus and hepatitis B suggest a postinfectious autoimmune response. There are no clear genetic links to PAN, but PAN-like vasculitis is part of reported monogenic autoinflammatory conditions. Key atypical features in this case include uveitis at presentation, nonspecific central neuroinflammation, unusual cutaneous lesion morphology, improvement of acute phase reactants before immunomodulatory treatment, and delayed biopsy wound healing. While ocular findings in PAN may include episcleritis, scleritis, keratitis, retinal vascular occlusions, and ocular ischemic syndrome, uveitis has not been reported in c-PAN. The patient also showed nonspecific inflammatory changes on initial MRI. Neurological involvement in c-PAN typically includes cerebrovascular accidents, cranial nerve palsies, and mononeuritis multiplex, with meningeal involvement being less common (reported 4% in a study of 69 children). Additionally, the patient experienced delayed wound healing following the biopsy, which is undocumented in c-PAN, but may be related to immune modulating treatment. A positive streptococcal throat swab could suggest an immune reaction as part of bacterial tonsilitis, or Acute Rheumatic Fever. However, he did not meet Jones Criteria, there was no response to prolonged antibiotics and the chronic remitting nature made these less likely. An autoinflammatory disorder, Deficiency of Adenosine Deaminase 2 (DADA2), was also considered but he had no evidence of livedo racemosa, strokes and no CECR1 mutation was identified. Our case has been discussed within a multidisciplinary team and we speculate that it could represent a previously undefined immune sensitivity within the autoimmune, autoinflammatory and immune deficiency spectrum giving an exaggerated response to infection. Key learning points • This case presents a significant diagnostic challenge due to its atypical clinical features and inconclusive extensive investigations, including immunologic testing, tissue biopsy, and genetic analysis. • While the patient’s symptoms improved with high-dose steroids and MMF, the recurrence of symptoms upon tapering steroids underscores the persistent inflammatory nature of the disease. • The detection of group A Streptococcus in the patient’s throat swab suggests a potential postinfectious autoimmune trigger, highlighting the role infections can play in the pathogenesis of vasculitis. The negative results from the R15 Primary Immunodeficiency panel suggest that more advanced genetic and immunologic testing may be beneficial. • We invite discussion on whether additional genetic or immunologic testing could optimise this patient’s care and contribute to the broader understanding of atypical vasculitis syndromes.

Impact of Age and Gender on Survival of Glioblastoma Multiforme Patients: A Multicenter Retrospective Study.

Glioblastoma multiforme (GBM) poses a significant health challenge as the most common primary malignancy of the adult central nervous system. Gender- and age-related differences in GBM influence prognosis and treatment complexities. This multicenter retrospective study explores gender and age disparities in GBM patients, investigating their impact on occurrence and survival outcomes. This multicenter retrospective study involved GBM patients treated in Guilan Province, Iran. Patients' data, including age, gender, tumor location, and histopathological diagnosis date, was collected from medical records. In a cohort of 164 GBM patients, the average age was 54.34 ± 14.16 years, with a higher prevalence among men (59.8%) and patients aged ≤ 60 years (64.6%). The tumor sites exhibited overlapping features in 68% of cases, with the frontal and temporal lobes being the most common specific locations. The mean survival was 12.88 ± 14.14 months, one-year survival of 45%, with women showing significantly higher one-year survival (60% vs. 40%) and longer mean survival (16.14 ± 17.35 vs. 10.75 ± 11.15 months). Furthermore, Patients ≤ 60 years had significantly higher one-year survival (75% vs. 35%). In subgroup analysis, women had significantly higher survival rates in patients ≤ 60 years. However, among patients over 60, women exhibited a more pronounced decline in survival rates, with no statistically significant difference between men and women in this age group. This study highlights that both age and gender significantly affect GBM survival outcomes. Younger patients, particularly women, exhibited better survival rates, while older patients, especially women, showed poorer outcomes. These findings suggest the need to stratify treatment approaches by both age and gender to optimize care and improve survival in GBM patients. Further research is recommended to explore these associations.

Primary Thyroid Malignancies in Children and Adolescents - A Retrospective Analysis from a Tertiary Cancer Centre in South India

Primary Thyroid Malignancies in Children and Adolescents - A Retrospective Analysis from a Tertiary Cancer Centre in South India

GNAQ/GNA11-Related Benign and Malignant Entities—A Common Histoembriologic Origin or a Tissue-Dependent Coincidence

Uveal melanoma (UM), recognized as the most prevalent primary intraocular malignancy in adults, is primarily driven by mutations in the GNAQ and GNA11 genes. These genetic alterations are also implicated in other conditions, which exhibit distinct morphological characteristics. In this article, we investigate the role of GNAQ and GNA11 mutations across varied disorders (e.g., UM, skin blue nevi, and hemangiomas), emphasizing the shared pathogenic mechanisms that connect them despite their differing clinical manifestations. By investigating the molecular pathways affected by these mutations, we provide insights into the potential for targeted therapies that could address not only UM but also other disorders associated with GNAQ/GNA11 mutations. Moreover, we discuss the role of SOX10-positive perivascular cells that may be implicated in the complex pathophysiology of GNAQ/GNA11-related entities. Understanding the common molecular foundation of these conditions opens new ways for research and treatment opportunities, potentially leading to more effective, personalized therapeutic strategies.

Surgery With or Without Radiotherapy Versus Radiotherapy Alone for Malignant Spinal Cord Compression: An Updated Meta-analysis.

A systematic review and meta-analysis. To conduct a meta-analysis of studies that compared surgery with or without radiotherapy to radiotherapy alone for patients with malignant spinal cord compression, and a subgroup analysis of patients stratified by hematologic and solid malignancies. Two previous meta-analyses showed that surgery with or without radiotherapy was better than radiotherapy alone in patients with malignant spinal cord compression. Nevertheless, there was no stratification by tumor type, leading to uncertainty regarding best approach for patients with hematologic malignancies. We searched PubMed, Scopus, and Web of Science, for studies comparing surgery with or without radiotherapy to radiotherapy alone in patients with malignant spinal cord compression. The primary outcomes were improvement in ambulatory status and survival at 12 months. For neurological outcomes, we included studies involving both locally advanced primary malignancies of the spine and metastatic tumors. We restricted our analysis to studies on metastases for survival outcomes. We included 2536 patients from 18 studies. Surgery was performed in 890 (35%) patients. The pooled analysis of all studies revealed that improvement in ambulatory status (OR 2.65; 95% CI 1.60-4.39) and survival at 12 months (OR 1.66; 95% CI 1.10-2.52) were significantly higher in patients who underwent surgery with or without radiotherapy. Improvement in ambulatory status (OR 1.92; 95% CI 1.19-3.09) and survival at 12 months (OR 4.24; 95% CI 2.35-7.66) were significantly higher in patients with hematologic malignancies in the surgical arm. The primary outcomes were not significantly different between patients with solid malignancies. Surgical intervention demonstrates superior neurological outcomes and increased survival compared with radiotherapy alone. Subgroup analysis revealed that patients with hematologic malignancies on surgery group experienced superior primary outcomes; however, high risk of bias of the included studies preclude definitive changes in standard care based on this data. These findings underscore the need for further research regarding the efficacy of surgical versus radiotherapeutic approaches for specific tumor types. 2.

Radiation Implication in Pediatric Second Primary Thyroid Malignancy (SPTM) Cumulative Incidence and Mortality in the United States: Large Cohort Evidence

Objective: To assess racial and sex variances in second primary thyroid malignancy (SPTM) cumulative incidence and temporal trends and the radiation exposure effect in pediatric SPTM. Materials and Methods: A retrospective cohort study, a non-experimental epidemiologic design, was used to assess the cumulative incidence (CmI) and temporal trends as well as the exposure effect of radiation in SPTM among children, 0–19 years, in the Surveillance, Epidemiology, and End Results (SEER) registry, National Cancer Institute (NCI), USA. Percent change (PC) and annual percent change (APC) were used to examine CmI rates and temporal trends, while chi-square statistics and binomial regression models were used to examine variable distribution by race and to determine the exposure effect of radiation on SPTM as well as mortality, respectively. Results: The frequency of pediatric thyroid cancer was (n = 3457) between 1973 and 2013/14, while the PC was 151.2 for all races but 99.8 among whites. Of all pediatric thyroid cancers diagnosed during this period, SPTM accounted for 3% (n = 99). Compared to whites, blacks/AA were 60% less likely to present with SPTM, adjusted risk ratio, aRR = 0.40, 99% CI 0.06–2.47, while other races were 18% more likely to develop SPTM, aRR = 1.18, 99% CI 0.48–2.87. Additionally, females relative to males were 63% less likely to be diagnosed with SPTM, aRR = 0.37, 99% CI 0.22–0.61. With respect to urbanicity, compared to children in rural areas, those in urban areas were 21% less likely to develop SPTM, aRR = 0.79, 99% CI, 0.12–5.35, while children in metropolitan areas were 40% less likely to develop SPTM, aRR = 0.60, 99% CI, 0.10–3.59. Although imprecise, there was a 5% increased risk of SPTM, with radiation as an exposure effect, aRR = 1.05, 99% CI 1.01–1.75. Conclusions: There are increasing temporal trends in pediatric SPTM with blacks relative to whites having observed lower incidence, despite an increasing percent change among blacks/AA, indicative of the disproportionate burden of this malignant neoplasm. SPTM risk was higher among males and in rural areas, while radiation as a risk for SPTM was clinically and biologically meaningful, albeit an observed statistically insignificant inference due to sampling variability, requiring intervention mapping in radiation exposure margination among children.

Added value of body MRI to detect primary abdominal malignancies in the diagnostic work-up of patients with adenocarcinoma of unknown primary

Abstract Purpose This study aimed to evaluate the added benefit of body MRI (covering the chest, abdomen, and pelvis) to detect the primary tumour in patients with adenocarcinoma of unknown primary (ACUP) and a suspected abdominal malignancy in whom previous diagnostic work-up with CT and/or FDG-PET/CT did not yield a primary tumour diagnosis. Methods Thirty ACUP patients with a suspected primary tumour in the abdomen/pelvis (based on pathology and/or pattern of disease) underwent MRI (T2-weighted, DWI, pre- and post-contrast T1-weighted) after completion of their initial diagnostic work-up with CT and/or PET/CT. Effects of MRI to establish a primary tumour diagnosis (and to detect additional metastatic sites) were documented. Integration of all available imaging data, additional diagnostic procedures (e.g., endoscopy), histopathology, and whole genome sequencing served as the composite standard of reference. Results MRI rendered a possible primary tumour diagnosis in 16/30 (53%) cases, which aligned with the final clinical diagnosis in 9/16 (56%) of these cases, thus resulting in a confirmed primary tumour diagnosis in 30% of our total patient cohort. These included four gastrointestinal, two hepatobiliary, one pancreatic, one ovarian and one breast cancer. MRI revealed extra metastatic sites in five patients (17%). Conclusion MRI can be of added value in the diagnostic work-up of ACUP patients with a suspected primary tumour originating from the abdomen or pelvis, in particular to detect gastrointestinal or hepatobiliary malignancies. Larger studies are needed to confirm these results and identify specific ACUP patients that are most likely to benefit from MRI. Key Points QuestionCan body MRI help identify the primary tumour in patients with adenocarcinoma of unknown primary (ACUP)? FindingsIn this pilot of n = 30 ACUP patients with clinically suspected abdominal malignancies, body MRI was able to establish the primary tumour in 30% of cases. Clinical relevanceBody MRI can be of added value (as an adjunct to CT and/or PET/CT) in the diagnostic work-up of ACUP patients with a suspected primary tumour originating from the abdomen or pelvis, especially to detect gastrointestinal or hepatobiliary malignancies.

Transmanubrial osteomuscular sparing approach: different indications for non-pulmonary malignancies.

The transmanubrial osteomuscular sparing approach (TMA) is recommended for surgeries involving or originating from the thoracic outlet structures. We present a series of consecutive patients treated from 2014 to 2024 who underwent oncological thoracic outlet surgery for primary or metastatic (non-pulmonary) malignancies. Overall, 33 patients were included. Our procedures resulted in no mortality, seven complications (21.2%) and all surgeries achieved radical (R0) status. In the hands of experienced professionals, the TMA approach proves to be safe and conservative, enabling radical surgery for tumors of the thoracic outlet. For low-grade tumors, it avoids the need for additional combined surgical access, while for high-grade tumors, it allows for more extensive en bloc resection.

Li–Fraumeni Syndrome: Narrative Review Through a Case Report with Ten Years of Primary Tumor Remission Associated with Sechium H387 07 Supplementation

There are hereditary mutations that predispose individuals to cancer development, such as pathogenic variants in the germ line of the tumor protein 53 (TP53) suppressor gene. This leads to a rare condition known as Li–Fraumeni syndrome (LFS), characterized by a high risk of developing multiple cancers throughout life by the precancerous niche that promotes the tumor microenvironment. LFS presents a significant challenge due to its limited therapeutic and chemoprophylactic options. Recently, protocols involving metformin as a prophylactic medication have been developed to target precancerous niches. However, this approach is still in the clinical phase, and no established therapeutic regimen is available. Therefore, new alternatives are needed to impact this disease effectively. Novel studies suggest that Sechium extract, rich in polyphenols, exhibits chemoprophylactic, antineoplastic, anti-inflammatory, and antioxidant activities, all involved in the tumor microenvironment of LFS. However, the specific role of Sechium extract in preventing recurrent neoplastic development in LFS remains unclear. We conducted this research through a case report of an LFS-diagnosed patient who has experienced multiple malignancies and cutaneous neoformations. This patient received a chemoprophylactic supplementation based on Sechium H387 07 extract over 11 years without reporting new primary malignancy events or recurrences, as evidenced by laboratory and positron emission tomography/computed tomography (PET/CT) studies. An extensive literature review on the disease, precancerous niche, tumor microenvironment, and potential mechanisms of Sechium H387 07 extract components was conducted to explain cancer absence in LFS. This review promotes the research and use of polyphenols as powerful chemoprophylactic agents to prevent and treat proliferative diseases like LFS.

ROR1 facilitates glioblastoma growth via stabilizing GRB2 to promote c-Fos expression in glioma stem cells.

Glioma stem cells (GSCs) are the root cause of tumorigenesis, recurrence, and therapeutic resistance in glioblastoma (GBM), the most prevalent and lethal type of primary adult brain malignancy. The exploitation of novel methods targeting GSCs is crucial for the treatment of GBM. In this study, we investigate the function of the novel ROR1-GRB2-c-Fos axis in GSCs maintenance and GBM progression. The expression characteristics of ROR1 in GBM and GSCs were assessed by bioinformatic analysis, patient specimens, and patient-derived GSCs. Lentivirus-mediated gene knockdown and overexpression were conducted to evaluate the effect of ROR1 on GSCs proliferation and self-renewal both in vitro and in vivo. The downstream signaling of ROR1 in GSCs maintenance was unbiasedly determined by RNA-seq and validated both in vitro and in vivo. Finally, rescue assays were performed to further validate the function of the ROR1-GRB2-c-Fos axis in GSCs maintenance and GBM progression. ROR1 is upregulated in GBM and preferentially expressed in GSCs. Disruption of ROR1 markedly impairs GSC proliferation and self-renewal, and inhibits GBM growth in vivo. Moreover, ROR1 stabilizes GRB2 by directly binding and reducing its lysosomal degradation, and ROR1 knockdown significantly inhibits GRB2/ERK/c-Fos signaling in GSCs. Importantly, ectopic expression of c-Fos counteracts the effects caused by ROR1 silencing both in vitro and in vivo. ROR1 plays essential roles in GSCs maintenance through binding to GRB2 and activation of ERK/c-Fos signaling, which highlights the therapeutic potential of targeting the ROR1-GRB2-c-Fos axis.

Synchronous primary gastric diffuse large B-cell lymphoma and multiple lung primary adenocarcinoma with pulmonary cryptococosis: a case report and literature review

BackgroundThe coexistence of non-Hodgkin’s lymphoma of the stomach and multiple primary lung adenocarcinomas with pulmonary cryptococcosis has rarely been reported.Case presentationWe herein present a 75-year-old man who was admitted to our hospital due to hematemesis. Gastroscopy and imaging revealed extensive stomach wall thickening and multiple lung lesions, including nodules and cavernous lesion. The patient was diagnosed with primary diffuse large B-cell lymphoma via gastroscopy and bilateral lung primary adenocarcinoma with cryptococcal infection via percutaneous CT-guided puncture biopsy. He subsequently underwent six cycles of R-CHOP regimen for gastric lymphoma, along with CT-guided radiofrequency ablation for the upper lobe of the right lung primary adenocarcinoma and radioactive particle implantation was performed on the lower lobe of the left lung primary adenocarcinoma, supplemented with antifungal therapy. After a definite diagnosis and systemic treatment, the patient was followed up for twenty-seven months with no tumor recurrence, progression or metastasis.ConclusionTo the best of our knowledge, the complex combination of multiple primary malignancies and pulmonary cryptococcal infection is extremely rare. The diagnosis is been confusing and challenging. CT-guided needle biopsy can help achieve pathological diagnosis, elucidate the type and stage of the tumor, and even change the clinical treatment strategy, which is necessary and beneficial.

Enhancing Radiation-induced Reactive Oxygen Species Generation Through Mitochondrial Transplantation in Human Glioblastoma.

Glioblastoma (GBM) is the most aggressive primary brain malignancy in adults, with high recurrence rates and resistance to standard therapies. This study explores mitochondrial transplantation as a novel method to enhance the radiobiological effect (RBE) of ionizing radiation (IR) by increasing mitochondrial density in GBM cells, potentially boosting reactive oxygen species (ROS) production and promoting radiation-induced cell death. Using cell-penetrating peptides (CPPs), mitochondria were transplanted into GBM cell lines U3020 and U3035. Transplanted mitochondria were successfully incorporated into recipient cells, increasing mitochondrial density significantly. Mitochondrial chimeric cells demonstrated enhanced ROS generation post-irradiation, as evidenced by increased electron paramagnetic resonance (EPR) signal intensity and fluorescent ROS assays. The transplanted mitochondria retained functionality and viability for up to 14 days, with mitochondrial DNA (mtDNA) sequencing confirming high transfection and retention rates. Notably, mitochondrial transplantation was feasible in radiation-resistant GBM cells, suggesting potential clinical applicability. These findings support mitochondrial transplantation as a promising strategy to overcome therapeutic resistance in GBM by amplifying ROS-mediated cytotoxicity, warranting further investigation into its efficacy and mechanisms in vivo .

Assessment of routine pre-operative group and save testing in patients undergoing cholecystectomy: a retrospective cohort study.

Routine group and save (G&S) testing is frequently performed prior to cholecystectomy, despite growing evidence that a targeted approach is safe and avoids unnecessary investigations. This retrospective cohort study explored frequency of testing in our unit, rates of peri-operative blood transfusion and pre-operative risk factors for requiring transfusion. Health records of 453 consecutive adults who underwent cholecystectomy in a UK NHS trust were reviewed for blood transfusion up to 30 days post-operatively. We compared the need for transfusion against patient demographics, indication and urgency of surgery, and the number of prior emergency hospital attendances with gallstone complications. Logistic regression determined whether prior attendances with complications of gallstones independently predicted the need for transfusion. Peri-operative blood transfusions within 30 days of operation occurred in 1.1% of cases, with no requirement for uncrossmatched blood. Patients who received a blood transfusion tended to have higher American Society of Anesthesiologists (ASA) grades ( p = 0.017), were more likely to have an underlying primary haematological malignancy (20.0% vs. 0.2%; p = 0.022) and prior emergency hospital attendances with gallstone complications (median 4 vs. 1; p < 0.001). Logistic regression showed each prior emergency attendance was associated with 4.6-fold odds of transfusion ( p = 0.019). Receiver operating characteristic curve analysis showed an area under the curve of 0.92. Three or more attendances predicted need for transfusion with 60.0% sensitivity and 98.0% specificity. 74% of patients had at least one G&S sample taken pre-operatively, costing the trust approximately £3,800 per year in materials. The findings of this study suggest that pre-operative G&S testing prior to cholecystectomy is not routinely required. Increased frequency of prior emergency hospital attendances with gallstone complications and co-morbidities associated with coagulopathies were pre-operative risk factors for post-operative blood transfusion. More selective testing could provide large financial savings for health institutions without compromising patient safety.

Management of Ureteral Stricture Disease After Radiation Therapy for Pelvic Malignancies: A Retrospective, Multi-Institutional Analysis

Objectives. A radiation-induced ureteral stricture (RIUS) is a challenging condition in urologic surgery, and the optimal surgical strategy is still a matter of debate. The aim of this study was to report post-operative outcomes of minimally invasive management of this condition from a multi-institutional cohort. Methods. Data of patients with diagnoses of RIUS at five referral robotic centers between January 2017 and December 2022 were retrospectively analyzed. Pre-, intra- and post-operative variables were collected. Recurrence was defined as the presence of flank pain combined with imaging findings for obstruction, and requiring further management. Univariate and multivariate logistic regression models were built to identify predictors of ureteral stricture recurrence. Results. Fifty-three patients with a diagnosis of an RIUS were included. Primary pelvic malignancy was mostly cervical (42%). In 72% of cases (mostly mid-proximal and short strictures) endourological management was attempted, which was deemed successful in 74% of patients at stent removal. The endourology success rate at a median follow-up of 12 months was 59%. Twenty-five patients (47%) were scheduled for robotic surgery. The reconstructive techniques most often performed were end-to-end anastomosis (44%) and ureteral reimplantation (52%). Three low-grade Clavien-Dindo post-operative complications (12%) occurred. Robotic surgery was successful in all cases except one. Considering the entire cohort, eight patients (15%) developed recurrence at a median follow-up of 5 months. All patients with recurrence were managed by permanent drainage. A statistically significant improvement in eGFR with respect to baseline was found at a median follow-up of 12 months (p = 0.007). The univariate logistic regression model identified ureteral stricture length &gt;2 cm (OR 6.4, 95% C.I. 1.1–36.9, p = 0.04) and concomitant chemotherapy (OR 8.9, 95% C.I. 1.6–49.9, p = 0.01) as predictors of recurrence. At multivariate analysis concomitant chemotherapy was confirmed as an independent predictor of recurrence (OR 7.8, 95% C.I. 1.3–49.0, p = 0.03). Conclusions. Endourological management of an RIUS is reasonable for short and mid-proximal ureteral strictures, while robotics is required in almost all the remaining cases. Up to 15% of recurrence develops within 6 months. Re-do reconstructive surgery is rarely performed, even in referral centers.

Tumor Microenvironment and Dermatological Conditions in Prostate Cancer

Tumor initiation, progression, and invasion are closely related to the tumor microenvironment. Inflammation can modulate the activity of the cells in the TME and contribute to all stages of tumor development. The etiopathogenesis of cutaneous manifestations associated with prostate cancer is unclear. The cutaneous phenotype associated with prostate cancer could be supported by intratumoral heterogeneity, the remodeling of interactions in the tumor microenvironment, and the dynamics of the epithelial–mesenchymal transition. Among the urinary system cancers, prostate cancer presents few cutaneous signs and symptoms, most being diagnosed in the advanced stages of the disease. In this review, we analyze the cutaneous events associated with prostate cancer, represented by direct or indirect manifestations of the primary malignancy and the skin toxicities caused by oncological medications.

Histology-Proven Gastrointestinal Metastasis from Nongastrointestinal Malignancies: Experience of This Rare Occurrence in a Single Center

Introduction Lymph nodes, lung, liver, bone, and brain are the commonest metastatic sites for malignancies arising in various body sites. Gastrointestinal (GI) tract is a very uncommon metastatic site and the present study describes the single-center experience of GI metastases from non-GI malignancies. Aims and Objectives To study the spectrum of metastatic tumors to GI tract and elucidate their clinicopathological characteristics. Materials and Methods This was a retrospective study done on cases diagnosed from 2015 to 2023 at our institute. All cases of non-GI malignancies metastatic to hollow GI tract were included. Cases with GI primary, hematological malignancies, cases with exclusive serosal deposits, and direct invasion of a GI organ from an adjacent primary tumor were excluded. Apart from hematoxylin &amp; eosin (H&amp;E)-stained slides, immunohistochemistry findings of these were reviewed. Results Thirty-six patients were histologically proven GI metastases from non-GI malignancies diagnosed during the study period. Most cases were seen in 5th to 7th decade with a significant female preponderance (M:F of 1:8). The commonest metastatic GI sites were small bowel (n = 11), sigmoid colon (n = 9), and rectum (n = 7), followed by stomach (n = 3), appendix (n = 3), gall bladder (n = 2), and ampulla (n = 1). Stricture, perforation, and nodular mucosa were the most common endoscopic findings. The most common primary malignancies in females were ovarian serous carcinoma (n =21) followed by squamous cell carcinoma (SCC) of cervix (n = 8). In males, there was no site preference, and the primary sites included prostate, lung, kidney, and oral mucosa. Conclusion The study highlights the rare occurrence of GI metastases from non-GI malignancies. Females are at greater risk of such metastases primarily from ovarian serous carcinoma and cervical SCCs.

Long-term follow-up of methotrexate and cytarabine in adult patients with Langerhans cell histiocytosis.

The optimal treatment strategy for adult Langerhans cell histiocytosis (LCH) remains unclear. Our previous study demonstrated the remarkable efficacy of combined methotrexate and cytarabine (Ara-C) [MA] therapy in patients newly diagnosed with LCH, with a median follow-up of 2 years. The present article reports long-term follow-up data spanning a median of 78 months (6.5 years) from a single-arm, single-centre, prospective phase 2 clinical trial (NCT02389400) conducted between January 2014 and December 2020. Ninety-five adults with newly diagnosed LCH exhibiting multisystem disease or multifocal single-system involvement underwent MA therapy every 35 days for six cycles. Methotrexate (1 g/m2) was administered by 24 h infusion on day 1 and AraC (0.1 g/m2) by 24 h infusion for 5 days. The primary end-point was event-free survival (EFS). The median patient age was 32 years (range 18-65 years). The overall response rate was 89.5%. Seven patients in this cohort died, and 38 experienced disease reactivation. No degenerative central nervous system diseases were observed. The estimated 6-year overall survival (OS) and EFS rates were 93.2% and 55.2% respectively. Multivariate analysis revealed that risk organ (RO) involvement at baseline (hazard ratio [HR] 6.135 [95% confidence interval (CI) 1.185-32.259]; p = 0.031) and age >40 years at diagnosis (HR 7.299 [95% CI 1.056-21.277]; p = 0.042) were associated with inferior OS. RO (HR 2.604 [95% CI 1.418-4.762]; p = 0.002) and skin (HR 2.232 [95% CI 1.171-4.255]; p = 0.015) involvement at baseline were poor prognostic factors for EFS. Regarding adverse events, four patients developed a second primary malignancy. In conclusion, the MA regimen was a valid and safe therapeutic approach for adult patients newly diagnosed with LCH.