Group Of Tumors Research Articles

Staining pattern of specific and cross-reacting Melan-A antibodies: A comparative study on 15,840 samples from 133 human tumor types.

The Melan-A (melanocyte antigen) protein, also termed 'melanoma antigen recognized by Tcells 1' (MART-1) is a protein with unknown function whose expression is specific for the melanocyte lineage. Antibodies against Melan-A are thus used for identifying melanocytic tumors, but some Melan-A antibodies show an additional - diagnostically useful - cross-reactivity against an unspecified protein involved in corticosteroid hormone synthesis. To comprehensively compare the staining patterns of a specific and a cross-reactive Melan-A antibody in normal and neoplastic tissues, tissue microarrays containing 15,840 samples from 133 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types were analyzed by immunohistochemistry. For the Melan-A-specific antibody 'Melan-A specific' (MSVA-900M), Melan-A positivity was seen in 96.0% of 25 benign nevi, 93.0% of 40 primary and 86.7% of 75 metastatic melanomas, 82.4% of 85 renal angiomyolipomas as well as 96.4% of 84 neurofibromas, 2.2% of 46 granular cell tumors, 1.0% of 104 schwannomas, and 1.1% of 87 leiomyosarcomas. The cross-reactive antibody 'Melan-A+' (MSVA-901M+) stained 98.1% of the tumors stained by 'Melan-A specific'. In addition, high positivity rates were seen in sex-cord-stroma tumors of the ovary (35.3%-100%) and the testis (86.7%) as well as for adrenocortical neoplasms (76.3%-83.0%). Only nine further tumor groups showed Melan-A+ staining, including five different categories of urothelial carcinomas. Our data provide a comprehensive overview on the staining patterns of specific and cross-reactive Melan-A antibodies. The data demonstrate that both antibodies are highly useful for their specific purpose. It is important for pathologists to distinguish these two Melan-A antibody subtypes for their daily work.

Ki67 is a better marker than PRAME in risk stratification of BAP1-positive and BAP1-loss uveal melanomas

BackgroundAccurate risk stratification of uveal melanoma (UM) patients is important for determining the interval and frequency of surveillance. Loss of BAP1 expression has been shown to be strongly associated with...

Paragangliomas of the head and neck

Paragangliomas represent a heterogeneous group of rare neuroendocrine tumors with marked variability in symptoms and disease course. Due to the close proximity to neurovascular structures, paragangliomas of the head and neck region can cause a variety of symptoms. To this day, there are no reliable prognostic factors that can predict apotentially malignant course. All patients with newly diagnosed paragangliomas should undergo an early diagnostic workup and regular follow-up examinations in specialized centers. While radical resection was previously regarded as standard treatment for paragangliomas, radiotherapy and active surveillance (watch-and-scan strategy) have become equally important over the years. Low-threshold techniques for molecular pathology analysis of the mutation-specific behavior of paragangliomas are nowadays available.

ALK-rearranged mesenchymal neoplasms: a clinicopathological and molecular study of eight additional cases of an emerging group of tyrosine kinase fusion mesenchymal tumours

AimsMesenchymal neoplasms characterised by ALK fusions mainly include inflammatory myofibroblastic tumour (IMT) and epithelioid fibrous histiocytoma (EFH). Most recently, ALK-rearranged mesenchymal tumours that are not IMT or EFH have been...

Tracking the Levels of Adiponectin and Interleukin-18 for Assessing the Efficiency of Chemotherapy in Suppressing Breast Cancer Progression

Breast cancer is a genetically and clinically heterogeneous disease. Cancerous cells multiplying abnormally in the breast, eventually spreading to the rest of the body if untreated. Breast cancer almost exclusively occurs in women. Cancer is a major public health problem worldwide with millions of new cancer patients diagnosed each year and many deaths resulting from this disease. Worldwide, female breast cancer has now surpassed lung cancer as the most commonly diagnosed cancer. SUBJECTS: Ninety two females were included in the current study, they were classified into three groups, depending on their health status (patients and healthy women) and the type of tumor suffered by the study patients: 32 female patients with cancerous breast tumors before receiving chemotherapy, 30 female patients with benign breast tumors (the pathological control group) and 30 females, who were included as a healthy control group. METHODS: Sandwich-ELISA method was applied to evaluate adiponectin and interleukin-18 concentrations in the sera of the study participants. RESULTS: Assessment of the adiponectin revealed a significant increase in the samples of malignant breast tumors group when compared with those of benign breast tumors (p=0.000) and healthy individuals (p=0.002). Interleukin-18 levels in the malignancy tumor group were significantly lower than their levels in the pathological (p=0.007) as well as healthy (p=0.000) controls groups. This study shows apparent slight decrease of adiponectin concentrations in cancerous patients group after getting approximately three consecutive doses of chemotherapy in comparison with its levels pretreatment, while non-significant difference was noted when comparing interleukin-18 levels after receiving the last dose of chemotherapy with its level before starting treatment. Although the levels of interleukin-18 increased after the end of the recommended course of chemotherapy, it did not rise to the levels of this protein in the healthy control group. The individual efficiency (sensitivity) of the evaluated criteria in the current study for distinguishing between cancerous and benign breast tumors was convergent. While the study recorded the highest specificity (93%) for adiponectin while the lowest specificity (40%) was recorded in interleukin-18. Adiponectin and interleukin-18 were able to distinguish 28 out of 32 breast cancer samples (88%).

Advancements in Neuroendocrine Neoplasms: Imaging and Future Frontiers.

Neuroendocrine neoplasms (NENs) are a diverse group of tumors with varying clinical behaviors. Their incidence has risen due to increased awareness, improved diagnostics, and aging populations. The 2019 World Health Organization classification emphasizes integrating radiology and histopathology to characterize NENs and create personalized treatment plans. Imaging methods like CT, MRI, and PET/CT are crucial for detection, staging, treatment planning, and monitoring, but each of them poses different interpretative challenges and none are immune to pitfalls. Treatment options include surgery, targeted therapies, and chemotherapy, based on the tumor type, stage, and patient-specific factors. This review aims to provide insights into the latest developments and challenges in NEN imaging, diagnosis, and management.

Relationship of adaptive subtyping and tumour heterogeneity of treatment response to neoadjuvant therapy in hormone receptor–positive HER2-negative early breast cancer: PENELOPE-B.

566 Background: The concept of intrinsic subtyping has been an important step for understanding of breast cancer (BC) as a heterogenous disease. However, these subtypes are not adapted to therapy-induced molecular plasticity. We have evaluated a high-risk luminal BC clinical trial cohort to identify new additional adaptive BC subtypes based on molecular alterations induced during neoadjuvant chemotherapy (NACT). Methods: A total of 1250 ER+/HER2- BC patients (pts) with residual disease after NACT and increased risk (CPS-EG score of ≥3 or 2 with ypN+) were randomized into the PENELOPE-B (NCT01864746) trial to receive palbociclib or placebo. Biomarker analysis was performed in 1411 pre- or postNACT tumor samples including 540 paired samples using the HTG EdgeSeq Oncology Biomarker Panel targeting 2549 genes (HTG Molecular Diagnostics Inc.), with assessment of the absolute assignment of breast cancer intrinsic molecular subtype (AIMS). For a subcohort of 29 pts, we evaluated triplicate samples before and after NACT as well as at the time of metastatic disease. Results: In paired biopsies, a total of 335 genes were significantly different between the pre- and the postNACT cohort. With hierarchical unsupervised clustering of these 335 genes, we characterized five different tumor subtypes with highly significant iDFS survival differences (p<0.0001, n=539). We identified two large groups of tumors with excellent prognosis (adaptive cluster AC1 and AC2, together n=284, 6 events), as well as two groups with a poor prognosis; AC-3 (n=163, 82 events) and AC-4 (n=78, 29 events). The worst prognosis was observed in a small group of tumors with a pre-NACT Basal/HER2E AIMS subtype (n=14, 11 events). AC1 and AC3 are enriched for tumors with an AIMS subtype change from LumB to LumA during NACT, with improved iDFS for AC1. AC2 and AC4 are enriched for tumors with a constant LumA AIMS subtype before and after NACT, with improved iDFS for AC2. The low-risk adaptive subtypes AC1 and AC2 cover a total of 52.7% of pts with a combined event rate of 2.1%. In contrast, the best pretherapeutic conventional AIMS-subtype, preNACT LumA, covers 51.7% of pts, but still has an event rate of 15.4%. This suggests that adaptive subtypes are superior to classical AIMS subtypes for prediction of survival after NACT in luminal BC. Conclusions: Classical approach of intrinsic subtyping relies on constant gene expression, limiting its scope. Adaptive subtyping can complement the classical approach, focusing on those genes that are changed during therapy. Comparison of paired samples before and after therapy is superior to classical subtyping of baseline samples. This approach identified large subgroups of pts with excellent prognosis after NACT despite clinical high risk. This can be an important step to focus on high-risk pts for new neoadjuvant and post-neoadjuvant therapy concepts.

Advancing rare cancer research by MALDI mass spectrometry imaging: Applications, challenges, and future perspectives in sarcoma.

MALDI mass spectrometry imaging (MALDI imaging) uniquely advances cancer research, by measuring spatial distribution of endogenous and exogenous molecules directly from tissue sections. These molecular maps provide valuable insights into basic and translational cancer research, including tumor biology, tumor microenvironment, biomarker identification, drug treatment, and patient stratification. Despite its advantages, MALDI imaging is underutilized in studying rare cancers. Sarcomas, a group of malignant mesenchymal tumors, pose unique challenges in medical research due to their complex heterogeneity and low incidence, resulting in understudied subtypes with suboptimal management and outcomes. In this review, we explore the applicability of MALDI imaging in sarcoma research, showcasing its value in understanding this highly heterogeneous and challenging rare cancer. We summarize all MALDI imaging studies in sarcoma to date, highlight their impact on key research fields, including molecular signatures, cancer heterogeneity, and drug studies. We address specific challenges encountered when employing MALDI imaging for sarcomas, and propose solutions, such as using formalin-fixed paraffin-embedded tissues, and multiplexed experiments, and considerations for multi-site studies and digital data sharing practices. Through this review, we aim to spark collaboration between MALDI imaging researchers and clinical colleagues, to deploy the unique capabilities of MALDI imaging in the context of sarcoma.

Epidemiology of undifferentiated sarcomas: A rare entity.

e23571 Background: Undifferentiated Sarcomas (USar), previously known as malignant fibrous histiocytomas, are a group of rare and diverse malignant tumors of mesenchymal origin with a prevalence of 0.08-1 per 100,000. These are aggressive tumors with often high-grade morphology. The diagnosis is made by exclusion of other sarcoma entities upon bone marrow biopsy (criteria listed below). Undifferentiated sarcomas are of four major types, i.e. Pleomorphic, Epithelioid, spindle and round cells. The exact etiology of these sarcomas remains obscure, although many signaling pathways with various genetic alterations may be implicated in their development. The goal of this epidemiologic study is to assist in better understanding of this lesser known aggressive malignancy. Methods: The data was collected from Surveillance, Epidemiology and End Result database Research Plus Data, 17 Registries, Nov 2022 Sub (2000-2020). We extracted undifferentiated sarcoma cases diagnosed between 0-90 years of age, using the ICD Code 8805/3. The analysis was stratified age, gender, race, & primary site labeled. The analysis was further completed by comparing survival using the Log-rank test (GraphPad Prism). Results: A total of 1680 cases of USar were identified, which were diagnosed between 2000 and 2020. Median age of diagnosis was 59.5 years. 50.54% were males and 49.46% were females. Of these cases, ~64.05% were Caucasians, ~15.18% Hispanics, ~10.48% Asians or Pacific Islanders, ~9.35% Black, and < 1% were Alaskan natives/American Indian and Non-Hispanics of unknown race. Further survival curves were compared based on gender, race and organ system. The average months of survival (MoS) based on gender showed no statistical significance (p value 0.6077). MoS calculated for Whites (28), Blacks (16), Asian & Pacific islanders (1), Alaskan natives & American-Indians (15), & Hispanics (21) (p value < 0.0001). MoS based on involved organ system were compared for: head/face/neck (18), GI tract (10), respiratory tract (4), heart/mediastinum/pleura (9), skin & soft tissue (51), bone (32), breast (30), GU (19), CNS (26), gynecological tract (12) and male reproductive system (29) (p < 0.0001). Conclusions: Undifferentiated Sarcoma accounts for less than 1% of all adult tumors. Only 1680 cases were found in the past twenty years, rendering it one of the rarest seen malignancies. Of the reported data, USar was most commonly observed in Caucasians. Comparing the survival curves also showed that there was no difference in survival based on gender. The highest MoS was seen in undifferentiated sarcomas of skin and soft tissues while respiratory tract tumors had the lowest average survival time. More research and analysis is warranted to understand this lesser known malignancy given its extremely low incidence.

Real world effectiveness of immunotherapy combined with anti-angiogenic therapy in patients with anthracycline-resistant soft tissue sarcomas.

e23543 Background: Soft tissue sarcomas are a heterogeneous group of malignant tumors of mesenchymal origin with more than 50 histologic subtypes. They have distinct molecular, genetic and clinical features and account for 1% of adult malignancies, the most common being liposarcoma, undifferentiated pleomorphic sarcoma and leiomyosarcoma. Immune checkpoint inhibitors (ICIs) have limited efficacy in sarcomas compared to other solid tumors; however, they have shown some activity in certain subtypes. The use of immunotherapy in sarcoma faces many challenges due to tumor heterogeneity, scarcity of therapeutic antibodies and chimeric antigen receptors to target antigens in sarcoma subtypes. However, combining ICIs with other therapies seems to improve the therapeutic efficacy to some extent. Antiangiogenic targeted therapy has been recommended by major guidelines as the treatment of choice for second-line soft tissue sarcomas. However, there are limited results from large clinical studies on whether immunotherapy combined with antiangiogenic therapy improves the efficacy. Methods: In this real-world single-center retrospective cohort study conducted at the First Affiliated Hospital of Zhejiang University School of Medicine, the efficacy of immunotherapy combined with antivascular therapy was assessed by progression-free survival (PFS) and overall survival (OS). Safety was assessed using the Common Terminology Criteria for Adverse Events version 5.0. Results: In this study, we enrolled a total of 21 eligible patients, of which 6 were liposarcoma, 4 were leiomyosarcoma, 4 were rhabdomyosarcoma, and 7 were other types. The immunotherapy used in all patients was anti-PD-1 antibody, with bevacizumab as the antivascular therapy drug in four of them and antiangiogenic tyrosine kinase inhibitors in the others. 12(57%) patients had received one-line therapy, 9 (43%) had received ≥ second-line therapy. Median progression-free survival (mPFS) was 5.5 months and median overall survival (mOS) 16.1 months in the total population. mPFS was significantly longer in 2nd-line V.S. ≥3rd-line patients (9.6 months V.S. 3.1 months, P = 0.0007), with a tendency to be prolonged mOS in 2nd-line treatment (16.1 months V.S. 9.3 months), but with no statistically significant difference. The most common grade ≥3 adverse events were hypertension, hand-foot syndrome, and abnormal thyroid function. Conclusions: This study confirms that immunotherapy combined with antiangiogenic therapy is effective and tolerable in anthracycline-resistant soft tissue sarcomas in the real world.It is possible that use in the second line may lead to better efficacy than use in multiple lines, and more clinical studies are expected.

Coagulation and fibrinolytic markers offer utility when distinguishing between benign and malignant gallbladder tumors: A cross-sectional study

BackgroundThe metabolic or proliferative abnormalities that are characteristic of tumor cells can lead to abnormal fibrinolysis or coagulation system activity, with certain tumors exhibiting hypercoagulability or existing in a fibrinolytic state. However, the utility of biomarkers of coagulation and fibrinolysis when seeking to differentiate between benign gallbladder disease and malignant gallbladder tumors remains uncertain. MethodsThis study included a total of 81 patients with benign gallbladder polyps and 94 patients with malignant gallbladder tumors. Pre-biopsy or pretreatment levels of PT, APTT, FIB, D-dimer, FDP, PLT, PIC, TAT, TM, and t-PAIC from these patients were compared using Mann-Whitney tests. The baseline data of the patients were analyzed using chi-square tests, and the diagnostic utility of these biomarkers in distinguishing between benign and malignant gallbladder lesions was evaluated using ROC curves, and Spearman correlation analysis was employed to assess the correlation between these indicators and tumor parameters. ResultsThe average age of malignant gallbladder tumor group was higher than benign gallbladder polyp group. And the base line analysis showed that there was a statistic difference in age, history of smoking, drinking, biliary tract disease, BMI of over weight between these two groups. In patients with malignant gallbladder tumors, FIB, D-dimer, FDP, PIC, TAT, TM, and t-PAIC levels were significantly elevated relative to those in patients affected by benign gallbladder polyp. The AUC for FIB, D-dimer, and FDP was 0.8469, 0.6514, 0.5950, while for PIC, TAT, TM, t-PAIC and four biomarker combined diagnosed was 0.8455, 0.6554, 0.7130, 0.6806, and 0.8859. Among these, TM was associated with the vascular invasion of tumor patients; TAT and t-PAIC were associated with neural invasion; D-dimer and FDP were related to the maximum tumor diameter; and FDP had a certain correlation with the tumor stage. ConclusionsIn gallbladder tumor patients, conventional coagulation metrics like FIB, D-dimer, and FDP, as well as newer thrombotic indicators such as PIC, TAT, TM, and t-PAIC, were obviously increased. Correlations with tumor parameters suggested their potential as biomarkers to distinguish benign from malignant gallbladder growths.

Lower Plasma Selenium Level in Primary Malignant Bone Tumors: A Survey Research

Objective: To compare plasma selenium levels in primary bone tumor patients with clinically healthy Thai subjects. Materials and Methods: A cross-sectional study on plasma selenium of primary bone tumor patients aged above 12 years old was obtained at Siriraj Hospital. The plasma samples were used for selenium assay by Electrothermal Atomic Absorption spectrometry method. The plasma selenium levels were compared with the clinically healthy Thai subjects or within primary bone tumor groups (age: below or above 30 years, gender: male or female, benign or malignant tumor, metastasis or non-metastasis). Results: One hundred and nine primary bone tumor patients were included in this study. Plasma selenium level in clinically healthy Thai subjects aged more than 30 years old was significantly higher than a primary bone tumor group (121.71 ± 19.96 g/L vs 111.88 ± 23.62 g/L, mean difference -9.83, p-value = 0.017). The plasma selenium levels within the primary bone tumor patients did not exhibit significant differences when compared across genders, age groups below and above 30 years old, benign and malignant tumors, or between metastatic and non-metastatic tumor cases. Conclusion: A patient with a history of malignant bone tumors tends to have a lower level of plasma selenium than normal people. However, the study of selenium supplementation for those who have a higher risk of developing malignant bone tumors is needed in the future.

Increased FGF2 expression promotes immune cell infiltration and correlates with an unfavorable prognosis in thyroid cancer

To delve into the expression and functions of FGF2 in patient with thyroid cancer (THCA), we conducted a systematic analysis of the association of FGF2 with immune cell infiltration, and prognosis in THCA patients. The transcription and protein levels, methylation, and biological properties of FGF2 were examined, along with its correlation with prognosis and immune cell infiltration in THCA patients using online databases UALCAN, Human Protein Atlas, Kaplan-Meier Plotter, DNMIVD, cBioPortal, GEPIA, Metascape, Linkedomics and TIMER. Clinical samples were collected for Western blot analyses. FGF2 was substantially overexpressed in the tumor group and shown correlations with age, tumor histology, nodal metastasis, and cancer stages. Moreover, higher expression of FGF2 (HR = 3.42, 95 % CI:1.57-7.44, p = 0.00099) was greatly correlated with poorer relapse-free survival in THCA patients, particularly in female patients. FGF2 methylation level was increased in the tumor group (p = 1.29E-6), and higher methylation levels of FGF2 were positively correlated with the poorer progression-free interval in THCA patients (p = 0.015). FGF2 mutations were markedly associated with shorter disease-free survival, with a mutation rate of 6 % among the total 498 THCA patients. FGF2 functions were potentially related to cell adhesion, cytokine-cytokine receptor interaction and angiogenesis. FGF2 expression showed positive correlations with the infiltration of B cells (Cor = 0.569, p = 1.04e-42), CD4+ T cells (Cor = 0.555, p = 9.43e-41), macrophages (Cor = 0.438, p = 2.94e-42), neutrophils (Cor = 0.578, p = 9.354e-45), and dendritic cells (Cor = 0.591, p = 5.00e-47). FGF2 is a potential prognostic marker in THCA patients, with its functions possibly related to cell adhesion, interaction of the cytokine-cytokine receptor, angiogenesis, and the promotion of multiple immune cell infiltration.

High-Resolution Raman Imaging of >300 Patient-Derived Cells from Nine Different Leukemia Subtypes: A Global Clustering Approach.

Leukemia comprises a diverse group of bone marrow tumors marked by cell proliferation. Current diagnosis involves identifying leukemia subtypes through visual assessment of blood and bone marrow smears, a subjective and time-consuming method. Our study introduces the characterization of different leukemia subtypes using a global clustering approach of Raman hyperspectral maps of cells. We analyzed bone marrow samples from 19 patients, each presenting one of nine distinct leukemia subtypes, by conducting high spatial resolution Raman imaging on 319 cells, generating over 1.3 million spectra in total. An automated preprocessing pipeline followed by a single-step global clustering approach performed over the entire data set identified relevant cellular components (cytoplasm, nucleus, carotenoids, myeloperoxidase (MPO), and hemoglobin (HB)) enabling the unsupervised creation of high-quality pseudostained images at the single-cell level. Furthermore, this approach provided a semiquantitative analysis of cellular component distribution, and multivariate analysis of clustering results revealed the potential of Raman imaging in leukemia research, highlighting both advantages and challenges associated with global clustering.

Unveiling the role of HP1α-HDAC1-STAT1 axis as a therapeutic target for HP1α-positive intrahepatic cholangiocarcinoma

BackgroundIntrahepatic cholangiocarcinoma (ICCA) is a heterogeneous group of malignant tumors characterized by high recurrence rate and poor prognosis. Heterochromatin Protein 1α (HP1α) is one of the most important nonhistone chromosomal proteins involved in transcriptional silencing via heterochromatin formation and structural maintenance. The effect of HP1α on the progression of ICCA remained unclear.MethodsThe effect on the proliferation of ICCA was detected by experiments in two cell lines and two ICCA mouse models. The interaction between HP1α and Histone Deacetylase 1 (HDAC1) was determined using Electrospray Ionization Mass Spectrometry (ESI-MS) and the binding mechanism was studied using immunoprecipitation assays (co-IP). The target gene was screened out by RNA sequencing (RNA-seq). The occupation of DNA binding proteins and histone modifications were predicted by bioinformatic methods and evaluated by Cleavage Under Targets and Tagmentation (CUT & Tag) and Chromatin immunoprecipitation (ChIP).ResultsHP1α was upregulated in intrahepatic cholangiocarcinoma (ICCA) tissues and regulated the proliferation of ICCA cells by inhibiting the interferon pathway in a Signal Transducer and Activator of Transcription 1 (STAT1)-dependent manner. Mechanistically, STAT1 is transcriptionally regulated by the HP1α-HDAC1 complex directly and epigenetically via promoter binding and changes in different histone modifications, as validated by high-throughput sequencing. Broad-spectrum HDAC inhibitor (HDACi) activates the interferon pathway and inhibits the proliferation of ICCA cells by downregulating HP1α and targeting the heterodimer. Broad-spectrum HDACi plus interferon preparation regimen was found to improve the antiproliferative effects and delay ICCA development in vivo and in vitro, which took advantage of basal activation as well as direct activation of the interferon pathway. HP1α participates in mediating the cellular resistance to both agents.ConclusionsHP1α-HDAC1 complex influences interferon pathway activation by directly and epigenetically regulating STAT1 in transcriptional level. The broad-spectrum HDACi plus interferon preparation regimen inhibits ICCA development, providing feasible strategies for ICCA treatment. Targeting the HP1α-HDAC1-STAT1 axis is a possible strategy for treating ICCA, especially HP1α-positive cases.

Pulmonary neuroendocrine tumors : Current review

Neuroendocrine neoplasms of the lung are aheterogenous tumor group. The pathological classification comprises diffuse idiopathic pulmonary neuroendocrine cell hyperplasia, classic neuroendocrine tumors, and neuroendocrine carcinoma. Classic neuroendocrine tumors include typical and atypical carcinoid tumors. Imaging plays an important role in diagnosis and can help in identifying the tumor biology. Overall, this tumor group is rare, comprising less than 2% of all thoracic tumors. In the current review, the various tumors are presented and important aspects regarding pathological classification, imaging modalities, and treatment are described.

Safety and surgical outcomes of robotic adrenalectomy from a 15-year experience at a single institution

Robotic adrenalectomy (RA) has gained significant popularity in the management of adrenal gland diseases. We report our experience at a single tertiary institution and evaluate the safety and surgical outcomes of RA. The data of 122 consecutive patients who underwent RA from October 2009 to December 2022 at Korea University Anam Hospital (Seoul, Korea) were reviewed. There were no perioperative complications. Clinicopathological features and surgical outcomes were retrospectively analyzed through complete chart reviews. Noteworthy findings include the influence of sex, tumor size, and body mass index on operation time, with the female and small tumor groups exhibiting shorter operation times (P = 0.018 and P = 0.009, respectively). Pheochromocytoma was identified as a significant independent risk factor for a longer operation time in the multivariate analysis [odds ratio (OR), 3.709; 95% confidence interval (CI), 1.127–12.205; P = 0.031]. A temporal analysis revealed a decreasing trend in mean operation times across consecutive groups, reflecting a learning curve associated with RA adoption. RA is a safe and effective operative technique alternative to laparoscopic adrenalectomy that has favorable surgical outcomes and enhances the convenience of the operation.

Overview of European standard clinical practice recommendations for multidiscplinary teams involved in the treatment of central nervous system tumours in children and adolescents – SIOPE Brain Tumour Group

Tumours of the central nervous system (CNS) represent the most common group of solid tumours in children and adolescents up to the age of 18 years. They comprise several biological entities, subgroups, and subtypes. These subtypes and additional factors, including age at diagnosis, location, stage, or genetic characteristics of the tumours result in a very heterogeneous spectrum of treatment-relevant strata for risk-adapted multimodal treatment recommendations, clinical courses, and long-term outcomes. Multidisciplinary teams with highly experienced members are needed to treat these children and adolescents to achieve the best possible outcome in the short and long-term. This is particularly important for the new CNS tumour entities with no established standard of care. On behalf of the Brain Tumour Group of the European Society for Paediatric Oncology, we summarize the key statements of the involved disciplines that need to cooperate in the diagnosis and risk-adapted treatment of children with CNS tumours: neuroradiology, neurosurgery, neuropathology, radiotherapy, endocrinology, neuro-ophthalmology, and quality of survival professionals, covering what should be considered standard clinical practice for diagnostic assessments, treatment modalities, and follow-up of children with CNS-tumours.

Resistance to immune checkpoint inhibitors in colorectal cancer with deficient mismatch repair/microsatellite instability: misdiagnosis, pseudoprogression and/or tumor heterogeneity?

Colorectal carcinoma (CRC) with deficiency of the deficient mismatch repair (dMMR) pathway/ microsatellite instability (MSI) is characterized by a high mutation load and infiltration of immune cells in the tumor microenvironment. In agreement with these findings, clinical trials have demonstrated a significant activity of immune checkpoint inhibitors (ICIs) in dMMR/MSI metastatic CRC (mCRC) patients and, more recently, in CRC patients with early disease undergoing neoadjuvant therapy. However, despite high response rates and durable clinical benefits, a fraction of mCRC patients, up to 30%, showed progressive disease when treated with single agent anti-programmed cell death 1 (PD-1) antibody. This article discusses the three main causes that have been associated with early progression of dMMR/MSI mCRC patients while on treatment with ICIs, i.e., misdiagnosis, pseudoprogression and tumor heterogeneity. While pseudoprogression probably does not play a relevant role, data from clinical studies demonstrate that some dMMR/MSI CRC cases with rapid progression on ICIs may be misdiagnosed, underlining the importance of correct diagnostics. More importantly, evidence suggests that dMMR/MSI mCRC is a heterogeneous group of tumors with different sensitivity to ICIs. Therefore, we propose novel diagnostic and therapeutic strategies to improve the outcome of dMMR/MSI CRC patients.

Interference with VIP to distinguish between real and false VIPoma:national study from the French Endocrine Tumors Group

Abstract Background Vasoactive Intestinal Peptide-secreting tumors (VIPomas) are digestive neuroendocrine tumors in which the hormonal secretion is life threatening. Biological confirmation is obtained by demonstrating an elevation in plasma VIP, usually using radioimmunoassay (RIA) method. In some cases, an analytical interference is suspected. We developed three different techniques to detect the interference in VIP RIA. Methods Three techniques were used: RIA after Sephadex column chromatography separation, RIA after Polyethylene Glycol (PEG) precipitation and125I-labelled VIP binding test. We included patients with suspicion of false positive VIP (FPV) elevation. We then compared results with those of a group of ‘real’, proven VIPoma (RV). Results A total of 15 patients with FPV elevation and 9 RV patients were included. Interference was detected in all FPV patients versus none in RV. Clinical and biochemical parameters did not differ between FPV and RV patients, but VIP concentration in RIA was significantly higher in FVP patients than in RV patients (228pmol/l vs 66 pmol/l, p=0.038). Using 125I-labelled VIP binding test, median proportion of radioactivity in the pellet was significantly higher in FVP than in RV patients (53% vs 13%, p < 0.0001). A 20.5% threshold presented excellent performances (Sensitivity 100% [79.6-100], specificity 100% [70.1-100]). Conclusions We developed three different laboratory techniques to reveal interference in RIA VIP assays. The diagnostic performance of all three was excellent. These techniques must be employed in cases of discordance between VIP elevation and clinical presentation.