Secondary Malignant Tumors Research Articles

Disseminated spontaneous postsplenectomy splenosis mimicking disseminated malignant tumor process. Clinical observation

This article is devoted to such a benign acquired condition as postsplenectomy splenosis, which is often incorrectly interpreted as a primary malignant tumor or secondary (metastatic) tumor process. The article provides a modern definition of the concept of «splenosis», examines the main mechanisms of autotransplantation of splenic tissue, indicates the most typical localizations of splenosis foci, provides the timing of the onset of splenosis, considers possible clinical manifestations and potential complications of this condition, discusses modern approaches to diagnostics, differential diagnostics of splenosis, tactics of management and treatment of such patients in detail, and also provides own author’s clinical observation of disseminated spontaneous postsplenectomy splenosis mimicking disseminated malignant tumor process. The feature of this clinical case is the presence of hereditary microspherocytosis (congenital microspherocytic hemolytic anemia, Minkowski-Chauffard disease) in the patient, which served as the reason for splenectomy. The article is illustrated with original computed tomography and magnetic resonance imaging.

QOL-18. MANAGING CANCER AND LIVING MEANINGFULLY (CALM) IN PRIMARY AND SECONDARY MALIGNANT BRAIN TUMOR PATIENTS: INTERIM ANALYSIS OF A PHASE IIC RANDOMIZED CONTROL PILOT TRIAL

Abstract BACKGROUND Patients with both primary and secondary brain tumors demonstrate substantial psychological distress but have been historically excluded from psychological research. Managing Cancer and Living Meaningfully (CALM), a supportive- expressive- psychotherapy, has proven to reduce depression and death-anxiety in advanced cancer patients but trials in neuro-oncology have been limited. Interim analyses (50% accrual) of the first randomized control pilot trial (RCT) of CALM in neuro-oncology are presented here. METHODS In this ongoing NIH ORBIT model Phase IIc pilot RCT, 60 adults with primary or secondary malignant brain tumors and heightened distress (PHQ/DADDS) are randomized (2:1) to a six-session CALM intervention or usual care. Data collection includes established feasibility and acceptability metrics, intervention satisfaction surveys and interviews, and clinically meaningful changes in distress severity scores across three timepoints (pre-, post-CALM, follow-up). RESULTS Of 64 patients screened, 36 were eligible and 32 enrolled (n=20 CALM, n=12 Control; 65% female; 90% White; Mage=46yrs). A multimodal recruitment model was used. Currently, assessment completion rates are: post-CALM (80%) and follow-up (67%). Reasons for withdrawal include disinterest in intervention topics (n=1) and lost to follow-up (n=1). Intervention retention is currently at 90%, with 8 participants still in active treatment. No adverse events have been documented. Perceived benefit appears high (4.1/5) and all participants report they would recommend CALM to others. Pre- to post-CALM, depression severity reductions appear equal across arms (CALM PHQ-9=30%; Control=33%) but death anxiety severity reductions appear more prevalent in the treatment group (CALM DADDS=70%; Control=50%). CONCLUSIONS Interim data suggests promising feasibility and acceptability results in this pilot RCT. Enrollment, retention, and assessment completion rates appear adequate. Participants are reporting high benefit and recommendation of CALM. Improvement in death anxiety appears greater in those treated with CALM compared to controls. These interim RCT findings are promising and suggest completion of the current phase.

Results of endoprosthesis of the elbow joint in patients with tumors of forming it bones

Background. The use of both individual and modular oncological endoprostheses of the elbow joint is possible with primary and secondary (metastatic) tumor lesions of the bones forming it. The purpose of the study was to assess the effectiveness of restoring the function of the elbow joint and the upper limb and improving the quality of life of the patient after endoprosthesis of the elbow joint due to tumors of the bones forming it. ­Material and methods. The results of the treatment of 14 patients who underwent endoprosthesis of the elbow joint due to tumors of the bones forming it were evaluated. Endoprosthesis was performed in 9 (64.3 %) subjects with primary bone tumors and in 5 (35.7 %) patients with metastatic tumors. Reconstruction of the elbow joint was performed with individual oncological endoprostheses in 10 (71.4 %) subjects and modular oncological endoprostheses in 4 (28.6 %) ones. Reconstruction was primary in 12 (85.7 %) patients and secondary in 2 (14.3 %) ones. Results. Du­ring follow-up, 4 (28.6 %) patients died from the progression of the main disease with an ave­rage follow-up period of 24.8 ± 11.9 months, the other 10 (71.4 %) were alive, with an average follow-up period of 80.8 ± 10.3 months. In the early postoperative period, the following complications were observed: neuropathy of the ulnar nerve in 1 (7.1 %) patient. In the late postoperative period, 1 (7.1 %) patient had an infectious complication after 14 months. 1 (7.1 %) subject developed aseptic loose­ning of the humeral leg of the endoprosthesis 12 months after endoprosthesis. In 1 (7.1 %) subjects with a metastatic tumor, local recurrence of the tumor was observed 9 months after surgery. Mean MEPS and MSTS functional scores were 80 and 72 %, respectively. The patients’ quality of life (according to the EORTQ-QLQ-С30 questionnaire) increased from 40 points in the preoperative period to 84 points after elbow joint replacement. Conclusions. Endoprosthesis of the elbow joint in the schemes of complex and combined treatment of primary and metastatic tumors of the bones forming it helps to improve the quality of life of this contingent of patients.

Skin organoid transplantation promotes tissue repair with scarless in frostbite.

Frostbite is the most common cold injury and is caused by both immediate cold-induced cell death and the gradual development of localized inflammation and tissue ischemia. Delayed healing of frostbite often leads to scar formation, which not only causes psychological distress but also tends to result in the development of secondary malignant tumors. Therefore, a rapid healing method for frostbite wounds is urgently needed. Herein, we used a mouse skin model of frostbite injury to evaluate the recovery process after frostbite. Moreover, single-cell transcriptomics was used to determine the patterns of changes in monocytes, macrophages, epidermal cells and fibroblasts during frostbite. Most importantly, human-induced pluripotent stem cell (hiPSC) -derived skin organoids combining with gelatin-hydrogel were constructed for the treatment of frostbite. The results showed that skin organoid treatment significantly accelerated wound healing by reducing early inflammation after frostbite and increasing the proportions of epidermal stem cells. Moreover, in the later stage of wound healing, skin organoids reduced the overall proportions of fibroblasts, significantly reduced fibroblast-to-myofibroblast transition by regulating the integrin α5β1-FAK pathway, and remodeled the extracellular matrix (ECM) through degradation and reassembly mechanisms, facilitating the restoration of physiological ECM and reducing the abundance of ECM associated with abnormal scar formation. These results highlight the potential application of organoids for promoting the reversal of frostbite-related injury and the recovery of skin functions. This study provides a new therapeutic alternative for patients suffering from disfigurement and skin dysfunction caused by frostbite.

Bengin Tuomrs of the Spine: A Systematic Review

Abstract Background Spine tumors are classified as primary tumors which originate from the spine itself and its adjacent structures and secondary (metastatic) tumors of distant organs which spread hematogenously and lymphatically and are located in the spine and its surrounding tissues. As the spine is well vascularized and has close relationship with regional lymphatic and venous drainage systems (especially Batson’s venous plexus), it is generally susceptible to metastasis. Metastatic tumors are the most common (97%) tumors of the spine. Aim of the Work to give an overview of the most important benign tumors of the spine, their clinical pictures and the typical features in imaging. Patients and Methods Search results will be conducted to systematic review management software and manually screened for eligibility to be included. PRISMA flowchart will be produced based on the search results and the inclusion/exclusion criteria. We will search the MED-LINE database, PubMed, Cochrane Bone and Muscle Trauma Group Specialized Register, Cochrane Register of Controlled Trails (The Cochrane Library) using the following keywords related to: Bengin tumors, spine. Results Giant cell tumors in the spine, particularly lumbar region, are rare but can present with pain and neurologic deficits. Osteoid osteomas and osteoblastomas, more common in the thoracolumbar spine, exhibit distinct radiological features. Osteoblastomas, locally aggressive, cause persistent pain, stiffness, and neurological deficits, often diagnosed in later stages. Spinal osteoblastoma diagnosis relies on CT scans, superior to plain radiography, and may necessitate biopsy for confirmation. Vertebral hemangiomas, usually asymptomatic, can cause compression-related symptoms and are identified through characteristic radiographic and CT appearances. Conclusion Searching the literature, Comparison between clinical picture in various types of begnin tumors we found that all begnin tumors have similar symptoms such as localized pain, neurological symptoms. Hence different methods of investigation should be used such as plain x-ray, CT scan and MRI.

OUTCOMES OF SHOULDER JOINT ENDOPROSTHETICS AFTER REMOVAL OF TUMORS IN THE HUMERUS

Introduction. The use of endoprostheses of the shoulder joint is possible with primary and secondary (metastatic) tumor lesions of the proximal part of the humerus. The possibility of using both individual oncological endoprostheses and modular oncological endoprostheses for tumors of the proximal part of the humerus is reported. Aim. To assess the effectiveness of restoring the function of the shoulder joint and upper limb and improving the patient's quality of life after shoulder joint arthroplasty for tumors of the proximal part of the humerus. Materials and methods. The results of the treatment of 27 patients who underwent shoulder arthroplasty in the conditions of the clinical departments of the "Institute of Traumatology and Orthopedics of the National Academy of Medical Sciences of Ukraine" for tumors of the proximal part of the humerus from 2014 to 2024 were evaluated. Endoprosthesis was performed in 22 (81.5%) patients with primary tumors of the proximal part of the humerus and in 5 (18.5%) with metastatic tumors. Endoprosthesis of the shoulder joint was performed with individual oncological endoprostheses in 24 (88.9%) patients and modular oncological endoprostheses in 3 (11.1%) patients. Arthroplasty was primary in 25 (92.6%) patients and secondary in 2 (7.4%) patients. Results. During follow-up, 3 (11.1%) patients died with an average follow-up period of 10.3±1.9 months, the other 24 (88.9%) were alive, with an average follow-up period of 88.1±8.7 months. The overall frequency of complications in our study was 6 (22.2%) cases, 3 (11.1%) patients had an infectious complication in the late postoperative period after 12, 24 and 36 months, 1 (3.7%) patient had aseptic loosening of the leg of the endoprosthesis after 36 months, in 2 (7.4%) patients after 5 and 6 months, dislocation of the head of the endoprosthesis from the joint cavity was noted. Local tumor recurrence was observed in 2 (7.4%) patients. The overall mean MSTS total limb functional outcome after shoulder arthroplasty for all 27 patients was 74.2%, and of the 24 patients who survived, the mean limb functional outcome after shoulder arthroplasty was 78.4%. The patients' quality of life (according to the EORTQ-QLQ-С30 questionnaire) increased from 32 points in the preoperative period to 78 points after shoulder joint replacement. Conclusions. Endoprosthetics is a modern method for reconstructing bone segments in the surgical treatment of tumors of long bones in the limbs. This method allows for the replacement of bone defects of any size (volume) and length. Shoulder joint endoprosthetics within the framework of combination and multimodal treatment of primary and metastatic tumors of the proximal part of the humerus provides restoration of both shoulder joint functions and the upper limb as a whole, thereby improving the quality of life for this group of patients.

Evolution of minimally invasive liver surgery in France over the last decade.

Despite evidence of benefits on postoperative outcomes, minimally invasive liver surgery (MILS) had a very low diffusion up to 2014, and recent evolution is unknown. Our aim was to analyze the recent diffusion and adoption of MILS and compare the trends in indications, extent of resection, and institutional practice with open liver surgery (OLS). We analyzed the French nationwide, exhaustive cohort of all patients undergoing a liver resection in France between January 1, 2013 and December 31, 2022. Average annual percentage changes (AAPC) in the incidence of MILS and OLS were compared using mixed-effects log-linear regression models. Time trends were analyzed in terms of extent of resection, indication, and institutional practice. MILS represented 25.2% of 74,671 liver resections and year incidence doubled from 16.5% in 2013 to 35.4% in 2022. The highest AAPC were observed among major liver resections [+ 22.2% (19.5; 24.9) per year], primary [+ 10.2% (8.5; 12.0) per year], and secondary malignant tumors [+ 9.9% (8.2; 11.6) per year]. The highest increase in MILS was observed in university hospitals [+ 14.7% (7.7; 22.2) per year] performing 48.8% of MILS and in very high-volume (> 150 procedures/year) hospitals [+ 12.1% (9.0; 15.3) per year] performing 19.7% of MILS. OLS AAPC decreased for all indications and institutions and accelerated over time from -1.8% (-3.9; -0.3) per year in 2013-2018 to -5.9% (-7.9; -3.9) per year in 2018-2022 (p = 0.013). This is the first reported trend reversal between MILS and OLS. MILS has considerably increased at a national scale, crossing the 20% tipping point of adoption rate as defined by the IDEAL framework.

QOL-42. ANALYSIS OF LATE EVENTS AFTER RADIATION THERAPY FOR PRIMARY PEDIATRIC BRAIN TUMORS

Abstract BACKGROUND Late events after radiation therapy for primary brain tumors consist of secondary malignant neoplasms (SMN) and tumor recurrences. The incidence and biology of late events are not very well described. Therefore, we aimed to identify late events in our institutional cohort and describe their biology. METHODS A retrospective chart review of all irradiated pediatric brain tumor patients treated between 2000 and 2015 at our institution was performed to obtain demographics and clinical data of late events. Late events were defined as intracranial intraaxial SMN or tumor recurrence occurring later than 3 years after radiation therapy. A whole-genome methylation array was employed to identify the methylation class of the late event. RESULTS In the observed period, 267 patients received some form of cranial radiotherapy for primary brain tumor; high-grade glioma (HGG, n=66), medulloblastoma (n=74), ependymoma (n=50), germ-cell tumors (GCT, n=22), low-grade glioma (LGG, n=24), and other diagnoses (n=31). Out of the 174 patients who were alive and without an event after 3 years from the radiation therapy, 30 developed late events (16.8%), and 27 of them were histologically verified. Verified late events consisted of 8 SMNs (29.6%) and 19 primary tumor recurrences. SMNs were mainly radiation-induced gliomas (RIG, n=7) and one atypical teratoid/rhabdoid tumor (ATRT) after craniopharyngioma. All RIG tumors clustered with the “pediatricHGG_RTK1” methylation class. Tumor recurrences consisted of medulloblastomas (Group 4 and Wnt), ependymomas (PFA and ST_ZFTA), GCTs, gliomas (one NF1-associated HGG, one H3-altered thalamic glioma, one diffuse astrocytoma with BRAF-V600E mutation), and craniopharyngiomas. The overall survival rate 5 years after a late event was 39.7%, with a worse survival rate for SMN patients (14.3%) compared to those with recurrences (44.9%) (p=0.05). CONCLUSIONS Late events affected 16.8% of long-term survivors. Strikingly, SMNs represented almost 30% of late events and were associated with a very poor prognosis.

A Role of Effector CD T Cells Against Circulating Tumor Cells Cloaked with Platelets: Insights from a Mathematical Model.

Cancer metastasis accounts for a majority of cancer-related deaths worldwide. Metastasis occurs when the primary tumor sheds cells into the blood and lymphatic circulation, thereby becoming circulating tumor cells (CTCs) that transverse through the circulatory system, extravasate the circulation and establish a secondary distant tumor. Accumulating evidence suggests that circulating effector CD T cells are able to recognize and attack arrested or extravasating CTCs, but this important antitumoral effect remains largely undefined. Recent studies highlighted the supporting role of activated platelets in CTCs's extravasation from the bloodstream, contributing to metastatic progression. In this work, a simple mathematical model describes how the primary tumor, CTCs, activated platelets and effector CD T cells participate in metastasis. The stability analysis reveals that for early dissemination of CTCs, effector CD T cells can present or keep secondary metastatic tumor burden at low equilibrium state. In contrast, for late dissemination of CTCs, effector CD T cells are unlikely to inhibit secondary tumor growth. Moreover, global sensitivity analysis demonstrates that the rate of the primary tumor growth, intravascular CTC proliferation, as well as the CD T cell proliferation, strongly affects the number of the secondary tumor cells. Additionally, model simulations indicate that an increase in CTC proliferation greatly contributes to tumor metastasis. Our simulations further illustrate that the higher the number of activated platelets on CTCs, the higher the probability of secondary tumor establishment. Intriguingly, from a mathematical immunology perspective, our simulations indicate that if the rate of effector CD T cell proliferation is high, then the secondary tumor formation can be considerably delayed, providing a window for adjuvant tumor control strategies. Collectively, our results suggest that the earlier the effector CD T cell response is enhanced the higher is the probability of preventing or delaying secondary tumor metastases.

The Pancreas as a Target of Metastasis from Renal Cell Carcinoma: Is Surgery Feasible and Safe? A Single-Center Experience in a High-Volume and Certified Pancreatic Surgery Center in Germany.

Background: Secondary malignant tumors of the pancreas are rare, representing 2-5% of all pancreatic malignancies. Nevertheless, the pancreas is one of the target organs in cases of metastatic clear cell renal cell carcinoma (CCRCC). Additionally, recurrent metastasis may occur. Surgical resection remains the best and prognostically most favorable therapeutic option in cases of solitary pancreatic metastasis. Aim: To review retrospectively the clinical tumor registry of the University Hospital of Magdeburg, Germany, for this rare entity, performing a clinical systematic single-center observational study (design). Methods: A retrospective cohort analysis of consecutive patients who had undergone pancreatic resection for metastatic CCRC was performed in a single high-volume certified center for pancreatic surgery in Germany from 2010 to 2022. Results: All patients (n = 17) included in this study had a metachronous metastasis from a CCRCC. Surgery was performed at a median time interval of 12 (range, 9-16) years after primary resection for CCRCC. All 17 patients were asymptomatic at the time of diagnosis. Three of those patients (17.6%) presented with recurrent metastasis in a different part of the pancreas during follow-up. In a total of 17 patients, including those with recurrent disease, a surgical resection was performed; Pancreatoduodenectomy was performed in 6 patients (35%); left pancreatectomy with splenectomy was performed in 7 patients (41%). The rest of the patients underwent either a spleen-preserving pancreatic tail resection, local resection of the tumor lesion or a total pancreatectomy. The postoperative mortality rate was 6%. Concerning histopathological findings, seven patients (41%) had multifocal metastasis. An R0 resection could be achieved in all cases. The overall survival at one, three and five years was 85%, 85% and 72%, respectively, during a median follow-up of 43 months. Conclusions: CCRC pancreatic metastases can occur many years after the initial treatment of the primary tumor. Surgery for such a malignancy seems feasible and safe; it offers very good short- and long-term outcomes, as indicated. A repeated pancreatic resection can also be safely performed.

Achievements and prospects for further development of photodynamic therapy technology in the treatment of cerebral tumors

Literature review reflects the current status and development status of intraoperative photodynamic therapy in neurooncology and discusses the results of the most important studies on photodynamic therapy (PDT). We searched the Pubmed, EMBASE, Cochrane Library and eLibrary databases for publications published between January 2000 and December 2022. Found 204 publications in foreign sources and 59 publications in domestic editions, dealing with the issues of photodynamic therapy in neurooncology. An analysis of the literature has shown that intraoperative PDT in neurooncology is an important tool that contributes to increasing the radicality of the operation and local control. The basic rationale for the effectiveness of PDT lies in the study of the pathways leading to the complete devitalization of a malignant tumor, the study of the mechanisms of the local and systemic immune response. In addition, subcellular targets in PDT are determined by the properties of photosensitizers (PS). Second generation PSs have already been introduced into clinical practice. The effectiveness of PDT using photoditazine, 5-aminolevulinic acid has been demonstrated. The mechanisms of action and targets of these PS have been established. In Russia, a number of studies have repeatedly shown and proved the clinical effectiveness of PDT in groups of neurooncological patients with glial tumors and secondary metastatic tumors, but so far, the method has not been included in the clinical guidelines for the provision of high-tech neurosurgical care. There is certainly a need for further development of PTD techniques in neurooncology, especially in patients at high risk of recurrence and aggressive CNS tumors.

Fine-needle aspiration diagnosis of secondary malignant tumors of the thyroid gland: A single-institution experience of 17 cases.

Fine-needle aspiration (FNA) is the most commonly used preoperative pathological diagnostic tool for thyroid tumors. Secondary malignant tumors of the thyroid gland account for less than 3% of all thyroid malignancies. The aim of this study was to investigate the types and cytopathological features of secondary thyroid tumors, evaluate diagnostic pitfalls in FNA. Cases of secondary thyroid tumors diagnosed in the Department of Pathology of Shaanxi Provincial People's Hospital were collected, and their clinical data, cytologic features, immunohistochemical results, and histopathological diagnoses were summarized. The study included 17 cases (8 males and 9 females) with a mean age of 60.4 ± 9.4 years (range, 45-83 years). Six cases had a known history of primary malignancy prior to FNA aspiration diagnosis. The most common organs of origin were the lungs (5 cases, 3 adenocarcinoma, and 2 small-cell carcinoma) and esophagus (5 cases, 3 squamous-cell carcinoma, 1 adenocarcinoma, and 1 small-cell carcinoma). The next most common was squamous-cell carcinoma of the larynx (3 cases), and gastric tumor (2 cases), including 1 lymphoma and 1 adenocarcinoma. Cell blocks and immunohistochemistry were performed in 12 of these cases. Comparison of the impact of positive history and IHC availability on the accuracy of pathologic diagnosis showed that both were statistically significant. FNA is an effective means of diagnosing secondary malignancies of the thyroid, in which knowledge of the patient's history of malignancy is essential, and the use of cell blocks and immunohistochemistry helps to clarify the pathological diagnosis.

En Bloc Surgery in the Thoracic Spine: Indications, Results, and Complications in a Series of Eighty-Five Patients Affected by Primary and Secondary Malignant Bone Tumors

BackgroundEn-bloc resection remains the cornerstone treatment for malignant bone tumors affecting the spine. The thoracic spine poses unique challenges due to the proximity of crucial structures. This study assesses outcomes of patients who underwent en-bloc spondylectomy for malignant bone tumors at the thoracic level. MethodsWe retrospectively reviewed 85 cases of primary and secondary bone tumors in the thoracic spine, undergoing en-bloc spondylectomy from 1996 to 2016. Evaluation encompassed clinical presentation, tumor characteristics, surgical outcomes, complications, survival rates, and recurrence. ResultsOf 85 patients, 40 presented directly, while 45 had undergone prior intralesional surgery. Chondrosarcoma and chordoma comprised the most prevalent primary histological types; thyroid and kidney carcinomas were the most frequent secondary tumors. Pain was reported in 75 patients at diagnosis. Margins were adequate in 54 cases and intralesional in 31. Immediate postoperative deaths amounted to four. Major complications included substantial blood loss, neurological deterioration, and paraplegia. The 5-year Local Recurrence-Free Survival rate was 58.7%, significantly influenced by the surgical margin: patients with wide margins experienced a 5-year LRFS of 85.7%, while those with marginal and intralesional margins had rates of 56.7% and 45.6%, respectively; overall recurrence was 22.3% with no notable disparities between previously treated and untreated patients. The 5-year Overall Survival (OS) rates were 63.2% and 56.2% for primary and secondary tumors, respectively. The OS was not significantly influenced by surgical margins. ConclusionsManaging malignant thoracic bone tumors poses significant challenges. This study underscores the criticality of achieving adequate margins, particularly following previous intralesional approaches.

Diagnostic Approach to and Differential Diagnosis of Clear Cell and Glandular Lesions of the Lower Urinary Tract.

A variety of glandular and clear cell lesions may be seen in the urinary bladder and/or urethra, ranging from benign to malignant primary and secondary tumors. Lesions with no malignant potential include reactive processes, such as nephrogenic metaplasia, and may show similar morphologic features as an infiltrative neoplasm, particularly in small biopsies. Similarly, ectopic tissues of Müllerian origin may be seen in the lower urinary tract, and their distinction from a true glandular neoplasm is essential to avoid overtreatment. A wide variety of primary and secondary malignant tumors exist with varying degrees of glandular and clear cell features. Therefore, surgical pathologists must be aware of the full scope of possible lesions to avoid misdiagnosis. To provide a practical framework for approaching the diagnosis of clear cell and glandular lesions of the urinary bladder/urethra and prostate, highlighting the strengths and limitations of various diagnostic features and ancillary tests. A review of the current literature was performed to obtain data regarding up-to-date diagnostic features and ancillary studies. In summary, distinct morphologic and immunohistochemical features and clinical and radiologic correlation are essential to establish an accurate diagnosis when such cases with glandular and clear features are encountered in the lower urinary tract.

Non-neoplastic astrocytes: key players for brain tumor progression.

Astrocytes are highly plastic cells whose activity is essential to maintain the cerebral homeostasis, regulating synaptogenesis and synaptic transmission, vascular and metabolic functions, ions, neuro- and gliotransmitters concentrations. In pathological conditions, astrocytes may undergo transient or long-lasting molecular and functional changes that contribute to disease resolution or exacerbation. In recent years, many studies demonstrated that non-neoplastic astrocytes are key cells of the tumor microenvironment that contribute to the pathogenesis of glioblastoma, the most common primary malignant brain tumor and of secondary metastatic brain tumors. This Mini Review covers the recent development of research on non-neoplastic astrocytes as tumor-modulators. Their double-edged capability to promote cancer progression or to represent potential tools to counteract brain tumors will be discussed.

Intraoperative Touch Imprint Cytology of Brain Neoplasms: A Useful High-Diagnostic Tool in 93 Consecutive Cases; Differential Diagnoses, Pitfalls, and Traps.

Intraoperative cytological examination of central nervous system (CNS) lesions was first introduced in 1920 by Eisenhardt and Cushing for rapid evaluation of neurosurgical specimens and to guide surgical treatment. It is recognized that this method not only confirms the adequacy of biopsy in CNS samples but also indicates the presence and preliminary diagnosis of lesional tissue. A total of 93 patients who underwent touch imprint cytology (TIC) for CNS tumors or lesions between 2018 and 2023 were included in the study. All cases were correlated with the final histopathological diagnosis, and pitfalls and difficulties encountered with discrepancies were noted. The most common primary CNS tumors were gliomas and meningiomas, while secondary (metastatic) tumors were predominantly lung, breast, and gastrointestinal system carcinomas. Sensitivity, specificity, positive predictive value, and negative predictive value for diagnosis with TIC were 94.1%, 100%, and 61.5%, respectively. Final histopathological diagnosis by TIC was made in 88 cases (94.6%) and the discrepancy was found in 5 cases (5.37%). Three of the five discrepancies (3.2%) were haematolymphoid malignancies (two lymphomas and one plasma cell neoplasia), one glioblastoma, and one hemangioblastoma case. TIC is a fast, safe, and inexpensive diagnostic tool used during intraoperative neuropathology consultation. Awareness of the pitfalls of using this method during intraoperative consultation will enable high-diagnostic accuracy.

Oncological results in primary and secondary malignant chest wall tumors.

This study aims to evaluate the oncological results of primary and secondary chest wall tumors treated with curative resections and to investigate possible prognostic factors. Between January 2010 and December 2021, a total of 77 patients (53 males, 24 females; median age: 59 years; range, 3 to 87 years) who underwent curative resection for malignant chest wall tumors were retrospectively analyzed. Each tumor was staged according to its histological type. Age, sex, tumor diameter, tumor type (primary/secondary), histological tumor type, grade, stage, complete resection, rib resection, reconstruction, neoadjuvant and adjuvant therapy, recurrence, and survival data were recorded. Of the chest wall tumors, 33 (42.9%) were primary and 44 (57.1%) were secondary (local invasion, metastasis). Nine (11.7%) patients had positive surgical margins. Chest wall resection was most commonly performed due to lung cancer invasion (46.8%), followed by Ewing sarcoma (13%). Recurrence was observed in 34 (44.2%) patients. The five-year recurrence-free survival rate was 42.7% and the five-year overall survival rate was 58.6%. There was no significant difference between the primary and secondary tumors in terms of recurrence-free and overall survival (p=0.663 and p=0.313, respectively). In the multivariate analysis, tumor grade and rib resection were found to be independent prognostic factors for both recurrence-free survival (p=0.005 and p<0.001, respectively) and overall survival (p=0.048 and p=0.007, respectively). Successful oncological results can be achieved in wellselected patients with primary and secondary chest wall tumors. The grade of the tumor should be taken into account while determining the neoadjuvant or adjuvant treatment approach and surgical margin width. Rib resection should not be avoided when necessary.

Secondary malignant tumors in surviving patients with neuroblastoma. The experience of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology

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Focused ultrasound combined with radiotherapy for malignant brain tumor: a preclinical and clinical study.

Blood-brain barrier (BBB) remains to be the major obstacle to conquer in treating patients with malignant brain tumors. Radiation therapy (RT), despite being the mainstay adjuvant modality regardless of BBB, the effect of radiation induced cell death is hindered by the hypoxic microenvironment. Focused ultrasound (FUS) combined with systemic microbubbles has been shown not only to open BBB but also potentially increased regional perfusion. However, no clinical study has investigated the combination of RT with FUS-BBB opening (RT-FUS). We aimed to provide preclinical evidence of RT-FUS combination in GBM animal model, and to report an interim analysis of an ongoing single arm, prospective, pilot study (NCT01628406) of combining RT-FUS for recurrent malignant high grade glioma patients, of whom re-RT was considered for disease control. In both preclinical and clinical studies, FUS-BBB opening was conducted within 2h before RT. Treatment responses were evaluated by objective response rate (ORR) using magnetic resonance imaging, progression free survival, and overall survival, and adverse events (AE) in clinical study. Survival analysis was performed in preclinical study and descriptive analysis was performed in clinical study. In mouse GBM model, the survival analysis showed RT-FUS (2Gy) group was significantly longer than RT (2Gy) group and control, but not RT (5Gy) group. In the pilot clinical trial, an interim analysis of six recurrent malignant high grade glioma patients underwent a total of 24 RT-FUS treatments was presented. Three patients had rapid disease progression at a mean of 33days after RT-FUS, while another three patients had at least stable disease (mean 323days) after RT-FUS with or without salvage chemotherapy or target therapy. One patient had partial response after RT-FUS, making the ORR of 16.7%. There was no FUS-related AEs, but one (16.7%) re-RT-related grade three radiation necrosis. Reirradiation is becoming an option after disease recurrence for both primary and secondary malignant brain tumors since systemic therapy significantly prolongs survival in cancer patients. The mechanism behind the synergistic effect of RT-FUS in preclinical model needs further study. The clinical evidence from the interim analysis of an ongoing clinical trial (NCT01628406) showed a combination of RT-FUS was safe (no FUS-related adverse effect). A comprehensive analysis of radiation dosimetry and FUS energy distribution is expected after completing the final recruitment.

Multiclass risk models for ovarian malignancy: an illustration of prediction uncertainty due to the choice of algorithm

BackgroundAssessing malignancy risk is important to choose appropriate management of ovarian tumors. We compared six algorithms to estimate the probabilities that an ovarian tumor is benign, borderline malignant, stage I primary invasive, stage II-IV primary invasive, or secondary metastatic.MethodsThis retrospective cohort study used 5909 patients recruited from 1999 to 2012 for model development, and 3199 patients recruited from 2012 to 2015 for model validation. Patients were recruited at oncology referral or general centers and underwent an ultrasound examination and surgery ≤ 120 days later. We developed models using standard multinomial logistic regression (MLR), Ridge MLR, random forest (RF), XGBoost, neural networks (NN), and support vector machines (SVM). We used nine clinical and ultrasound predictors but developed models with or without CA125.ResultsMost tumors were benign (3980 in development and 1688 in validation data), secondary metastatic tumors were least common (246 and 172). The c-statistic (AUROC) to discriminate benign from any type of malignant tumor ranged from 0.89 to 0.92 for models with CA125, from 0.89 to 0.91 for models without. The multiclass c-statistic ranged from 0.41 (SVM) to 0.55 (XGBoost) for models with CA125, and from 0.42 (SVM) to 0.51 (standard MLR) for models without. Multiclass calibration was best for RF and XGBoost. Estimated probabilities for a benign tumor in the same patient often differed by more than 0.2 (20% points) depending on the model. Net Benefit for diagnosing malignancy was similar for algorithms at the commonly used 10% risk threshold, but was slightly higher for RF at higher thresholds. Comparing models, between 3% (XGBoost vs. NN, with CA125) and 30% (NN vs. SVM, without CA125) of patients fell on opposite sides of the 10% threshold.ConclusionAlthough several models had similarly good performance, individual probability estimates varied substantially.