Resection Therapy Research Articles

Unraveling molecular signatures and prognostic biomarkers in glioblastoma: a comprehensive study on treatment resistance and personalized strategies

BackgroundGlioblastoma (GBM) is a highly aggressive primary brain tumor with limited treatment success and poor prognosis. Despite surgical resection and adjuvant therapies, GBM often recurs, and resistance to radiotherapy and temozolomide presents significant challenges. This study aimed to elucidate molecular signatures associated with treatment responses, identify potential biomarkers, and enhance personalized treatment strategies for GBM.MethodsWe conducted a comprehensive analysis using the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. The GEO dataset (GSE206225) was used to identify differentially expressed genes (DEGs) between radiation-sensitive/resistant and temozolomide-sensitive/resistant GBM samples. TCGA data were utilized for subsequent analyses, including Lasso-Cox regression, risk score model construction, Kaplan–Meier survival analysis, and gene set enrichment analysis (GSEA). Hub genes were identified through survival analysis, and a gene prognostic nomogram was developed. Additionally, validation of the three-gene risk signature through multiple external cohorts and validation of protein expression levels were performed.ResultsDEG analysis identified 111 genes associated with chemoradiotherapy resistance, providing insights into the complex landscape of GBM treatment response. The risk score model effectively stratified patients, showing significant differences in overall survival and progression-free survival. GSEA offered a deeper understanding of pathway activities, emphasizing the intricate molecular mechanisms involved. NNAT, IGFBP6, and CYGB were identified as hub genes, and a gene prognostic nomogram demonstrated predictive accuracy.ConclusionThis study sheds light on the molecular intricacies governing GBM treatment response. The identified hub genes and the gene prognostic nomogram offer valuable tools for predicting patient outcomes and guiding personalized treatment strategies. These findings contribute to advancing our understanding of GBM biology and may pave the way for improved clinical management.

Lung Cancer with Brain Metastasis—Treatment Strategies and Molecular Characteristics

Lung cancer is a leading cause of brain metastases (BMs), with 10–20% of patients with non-small cell lung cancer (NSCLC) presenting with BMs at diagnosis and 25–50% developing them over the course of their disease. Historically, BMs have posed significant therapeutic challenges, partly due to the blood brain barrier (BBB), which restricts drug penetration to the central nervous system. Consequently, BMs were initially managed with local treatments, including surgical resection, stereotactic radiosurgery, and whole brain radiation therapy. In recent years, however, systemic treatments for BMs have advanced significantly, particularly with the development of molecularly-targeted therapies and immunotherapies. The discovery of driver mutations and the development of novel tyrosine kinase inhibitors (TKIs) have yielded encouraging intracranial responses in NSCLC patients with actionable genetic alterations (e.g., EGFR, ALK, ROS1). Genomic profiling has also suggested genetic heterogeneity between BMs and primary sites. Immunotherapies, alone or in combination with other treatments, have demonstrated promising results in NSCLC with BMs, although most clinical trials have included only selected patients with asymptomatic or previously treated BMs. In this review, we discuss the molecular and immune characteristics of NSCLC with BMs, analyze intracranial efficacy findings from clinical trials, and explore treatment strategies for lung cancer patients with BMs.

A new nonsense mutation of PTCH1 gene in mother and daughter with late-onset nevus basal cell carcinoma syndrome: Case report.

Nevoid basal cell carcinoma syndrome (NBCCS) is a rare clinical disease characterized by a disproportionate number of basal cell carcinoma to sun exposure and skin types. Patched 1 (PTCH1) gene is proposed to be implicated in the pathogenesis of NBCCS. This study aimed to investigate whether PTCH1 gene is the causative gene in Chinese patients with NBCCS. Here we detected the first nonsense mutation in PTCH1 gene by Sanger sequencing of blood samples from a mother and her second daughter (NM000264: exon14: c.2080C>T: p.Q694X). Both of the mother and her second daughter had ovarian mature teratomas. The mother received liquid nitrogen cryotherapy, surgical resection, and radiation therapy, while her second daughter was treated with a GX-III multifunctional ion surgical therapy machine and surgery. New rashes continued to appear and contractures of the right eyelid healed in the mother, while her second daughter had multiple pitting depressions on the palms and soles of both hands and feet. We detected a new mutation in PTCH1 gene in 2 patients with NBCCS, and both of them had ovarian mature teratomas, which are related to NM000264: exon14: c.2080C>T: p.Q694X.

Treatment Options for IDH-Mutant Malignant Gliomas.

As the peak incidence of isocitrate dehydrogenase (IDH)-mutant gliomas is amongst young adults, there is a need to balance tumor control with long term side effects of therapy. Following initial clinical presentation and acquisition of contrasted diagnostic imaging, tissue diagnosis is essential in suspected diffuse glioma. Depending on the location and extent of disease, maximal surgical resection is preferred both for histologic diagnosis and initial therapy. Partial resection or biopsy alone is considered when the tumor cannot be completely resected or if there are clinical reservations regarding a more significant operation. The classification of diffuse glioma has evolved over time, with histopathology and molecular marker status guiding discussions of prognosis and postoperative management. In patients with IDH-mutant grade 2 glioma and low-risk features, observation with active surveillance is generally recommended following a gross total resection. For those with high-risk features, which historically included age > 40years or subtotal resection, adjuvant chemotherapy and radiation therapy are generally recommended, however decisions for adjuvant therapy pose challenges as many of the landmark historical trials guiding adjuvant therapy were performed prior to the molecularly defined era. This is an area where multiple clinical trials are ongoing and hold promise to inform treatment paradigms, including recent data on the use of IDH-mutant inhibitors in grade 2 tumors with recurrent or residual disease. For IDH-mutant grade 3 and 4 glioma, adjuvant chemotherapy and radiation are recommended for all patients after initial resection.

Pushing boundaries: simultaneous minimal-invasive resection of complex colorectal liver metastases and its primary tumor.

Synchronous liver metastases occur in approximately 15-20% of patients with colorectal cancer. Optimal oncological treatment of oligometastatic disease combines surgical resection and systemic therapy. Open simultaneous resection of the primary and liver metastases is well described, but there is not much evidence for the increasing use of the minimally invasive approach. We here report the results of our experience of simultaneous minimally invasive resections. A prospective database of patients with resection of colorectal liver metastases (CRLM) at the Charité - Universitätsmedizin Berlin was used for retrospective data analysis. We report all patients undergoing simultaneous minimal invasive resection of colorectal cancer and its synchronous liver metastases between May 2015 and December 2021. Out of 281 patients undergoing resection of CRLM, 33 (11.7%) patients had simultaneous minimal invasive resection of the colorectal primary. The primary tumor was located mostly within the rectum (n = 17; 48.6%), followed by the descending colon (n = 6; 17.1%). CRLM were localized in both liver lobes in 69.7% (n = 23) of cases. Following resection of the colorectal tumor, an anastomosis was performed in 31 of 33 patients (93.9%), with no anastomotic leakage observed in the follow up. Simultaneous liver resections were performed mostly as subsegment (n = 20) or bisegment resections (n = 11). Mean IWATE-Score of all hepatic resections was 5.5 (± 2.4). Complication rates (Clavien-Dindo ≥ 3) were similar compared between low/intermediate and advanced/expert difficulty for liver resection (n = 4, 17.4% vs. n = 2, 20.0%; p = 1.0). In one case conversion to open resection was required. Our data indicate that simultaneous minimal invasive resection of CRLM and the primary tumor is a safe and feasible procedure. Complication rates were consistent across different levels of difficulty (low to expert) in liver resections. Therefore, indications for simultaneous resection may be expanded.

Endoscopic Local Excision (ELE) with Knife-Assisted Resection (KAR) Techniques Followed by Adjuvant Radiotherapy and/or Chemotherapy for Invasive (T1bsm2,3/T2) Early Rectal Cancer: A Multicenter Retrospective Cohort.

Background: Resected rectal polyps with deep invasion into the submucosa (pT1b-sm2,3) or the muscle layer (pT2) are currently confronted with surgery due to non-curative resection. Aims: We evaluated the efficacy, safety, and locoregional control of adjuvant radiotherapy (RT) and/or chemotherapy (CT) following endoscopic KAR (knife-assisted resection) in patients with invasive early rectal cancers who are unwilling or unsuitable for additional surgical resection. Methods: Fifty-one patients with early rectal cancers, pT1b or pT2, underwent post-resection adjuvant RT and/or CT in 15 centers worldwide. "En bloc" macroscopic resection, R0 resection, recurrence rate, and adverse events following resection and adjuvant therapy were recorded in a multicenter retrospective cohort study. Results: Diagnostic staging (38/51, 75%) was the main reason for ELE. Macroscopic "en bloc" resection was demonstrated in 50/51 (98%), with an average follow-up of 20.6 months. Endoscopic recurrence occurred in 7/51 (13.7%) of patients, with mean time for diagnosis of recurrence at 8.9 months. Adjuvant therapy consisted of RT in 49.0% (25/51), CT in 11.8% (6/51), and combined CRT in 39.2% (20/51) of the cases. Perforation, severe post-procedural bleeding, and incontinence were the most frequent complications. The absence of superficial ulceration was associated with macroscopic complete resection, while the lesions with lower budding stage, clear lateral margins, lesion size < 40 mm, and needle-type knife used were associated with less endoscopic recurrencies. Conclusions: Our data investigated adjuvant RT and/or CT after endoscopic KAR of infiltrative rectal cancers (pT1bsm2,3-pT2) as being safe and effective for locoregional control and providing a non-surgical treatment option for patients with a non-curative resection.

ASO Visual Abstract: Comparison of Prognostic Outcomes Between Repeat Liver Resection and Particle Therapy for Patients with Recurrent Hepatocellular Carcinoma.

ASO Visual Abstract: Comparison of Prognostic Outcomes Between Repeat Liver Resection and Particle Therapy for Patients with Recurrent Hepatocellular Carcinoma.

Abstract B031: Immune cell composition in surgical drain fluid as a novel prognostic marker in head and neck squamous cell carcinoma

Abstract Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy globally, and the vast majority of cases are treated with primary surgical resection and adjuvant therapy. Our group has pioneered the use of HNSCC circulating tumor DNA (ctDNA) in surgical effluent collected postoperatively from surgical drains (surgical drain fluid, SDF) as a novel proximal bioanalyte for measuring minimal residual disease after surgery. We now profile the immune cell composition of SDF compared to paired peripheral blood mononuclear cells (PBMCs), and correlate SDF immune cell profiles with clinical variables and oncologic outcomes in HNSCC. Method: SDF and peripheral venous blood were collected 24 hours postoperatively from 58 HNSCC patients, including 11 HPV (+) and 47 HPV (-) patients undergoing standard of care surgical resection, lymph node dissection, and adjuvant therapy. Freshly collected SDF cells and PBMCs were cryopreserved until profiling by multicolor flow cytometry for respective leukocyte compositions. Analyses were used to define the following viable CD45+ leukocyte subsets: total T cells, CD4 T-cells CD8 T-cells, Treg cells, B-cells, non- classical monocytes, classical monocytes, natural killer (NK) cells, classical dendritic cells (cDC), plasmacytoid DC (pDC), macrophages, and monocytic myeloid-derived suppressive cells (MDSCs). Immune cell percentages were correlated with clinical characteristics and cancer recurrence. Results: CD45+ leukocytes comprised &amp;gt;99.5% of SDF cells, with very few EPCAM+ tumor cells (&amp;lt; 10^-4). HPV status did not significantly affect SDF immune cell composition, and no significant differences were noted by tumor site (larynx, oral cavity, oropharynx), or extracapsular lymph node extension. Among 13 HPV (-) HNSCC patients with paired peripheral blood drawn concurrently, SDF had a higher proportion of B-cells(16.8% vs. 9%, p=0.044), NK cells(56% vs. 12%, P&amp;lt;0.001), monocytes(14% vs. 1%, P&amp;lt;0.001), and macrophages(3.1% vs. 0.46%, P&amp;lt;0.001) compared to PBMCs, and a lower proportion of CD4+ T cells(1% vs. 24%, P&amp;lt;0.001), CD8+ T cells(0.6% vs. 18%, P&amp;lt;0.001), MDSCs(2.1% vs. 3.4%, P=0.029), and pDCs(0.1% vs. 0.2%, P=0.014). HPV (-) HNSCC patients that went on to recur (n=9) had a significantly higher proportions of SDF monocytes (total, classical, and non- classical) and CD56dimCD16+ NK cells (all P&amp;lt;0.001) compared to non-recurrent patients (n=38). Patients who went on to recur also had a significantly lower proportion of SDF B-cells (P&amp;lt;0.001), CD56bright NK cells(P=0.01), and macrophages (P=0.018) compared to non- recurrent cases. No significant differences were noted with respect to proportions of CD3+, CD4+, CD8+ T-cells, DC, and MDSC cells. Conclusion: SDF from HNSCC patients contains unique immune cell populations and may provide new insights into postoperative tumor immunity. Differences in SDF immune cell composition by oncologic outcome in patients that go on to recur, highlighting potential prognostic and predictive applications of SDF immune cell profiling for adjuvant therapy decision-making. Citation Format: Zhongping Xu, Noah Earland, Lucien Khalil, Lazar Vujanovic, Danny Azmi Elias, Riyue Bao, Jason J. Luke, Aadel A. Chaudhuri, Jose P. Zevallos. Immune cell composition in surgical drain fluid as a novel prognostic marker in head and neck squamous cell carcinoma [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B031.

CCRG-04. RIBOCICLIB RESPONSIVE MENINGIOMA IN THE TREATMENT OF BREAST CANCER

Abstract BACKGROUND Meningiomas are the most common primary intracranial tumors, typically managed with surgical resection and/or radiation therapy. Systemic therapy options are limited and reserved for cases refractory to conventional interventions. Cyclin dependent kinase (CDK) proteins are key cell cycle regulators. CDK inhibitors are clinically available, approved for treatment of breast cancer and in clinical trials for meningioma. METHODS We present a case where a patient with incidentally-discovered intracranial meningioma undergoing CDK inhibitor therapy with ribociclib for breast cancer experienced a radiographic response. RESULTS A 73-year-old female was diagnosed with estrogen receptor (ER) positive, progesterone receptor (PR) positive, HER2 negative metastatic invasive ductal carcinoma of the breast. She was treated with estrogen receptor antagonist fulvestrant and CDK 4/6 inhibitor ribociclib. MRI of the brain performed for disease staging demonstrated an extraaxial, dural-based, homogenously enhancing mass along the left posterior petrous ridge consistent with a meningioma. Two-month interval scan demonstrated a marginal decrease in size of the mass (15.6x18.3 mm to 15.4x17.5 mm). Systemic disease related to breast cancer concurrently improved. Two years later, with ongoing fulvestrant and ribociclib therapy, a repeat MRI brain demonstrated further decrease in size of the meningioma (13.4x16.8 mm). CONCLUSIONS Hormonally-directed therapies previously demonstrated limited benefit for meningiomas despite PR/ER positivity reported for these tumors. However, CDK 4/6 inhibitors abemaciclib and ribociclib have demonstrated activity in treatment of recurrent grade 2/3 meningiomas. The radiographic response noted in our case suggests there may be a role for systemic therapy even in treatment-naive cases that may not be amenable to surgical resection or radiation therapy.

Limfatičke malformacije

Lymphatic malformations are abnormal cystic dilatations of lymphatic vessels. They are present at birth, but often can only be detected later in life. Simple lymphatic malformations are limited to certain anatomical regions, while complex diffuse abnormalities can affect the entire organism. Simple lymphatic malformations are divided into macrocystic (cysts &gt;1cm) and microcystic (cysts &lt;1cm). According to the ISSVA classification from 2015, the term lymphangioma is abandoned and the term lymphatic malformation is introduced, which is intended to clearly indicate that it is not a tumor formation. The clinical course is characterized by long asymptomatic periods with short-term inflammatory or infectious episodes and episodes of intracystic bleeding. In the case of voluminous changes, the diagnosis can be made at the transition from the second to the third trimester of pregnancy by ultrasound examination or fetal magnetic resonance. Ultrasound and magnetic resonance imaging are diagnostic methods of choice in the postpartum period as well. The purpose of the treatment is not to completely remove the formation, but to limit the symptoms to the extent that would preserve functionality and provide an appropriate appearance. Treatment methods are the expectant method for asymptomatic disease, sclerotherapy, surgical resection, drug treatment, laser treatment and physical therapy measures. When there is no life-threatening airway obstruction, sclerosing is the method of choice. Bleomycin as a sclerosant provides good results with mild side effects. Therapy with rapamycin (sirolimus) allows for a large percentage of reduction in formation, but it is important to monitor possible side effects

SURG-54. RECURRENT BRAIN METASTASES (RBM) TREATED WITH SURGICALLY TARGETED RADIATION THERAPY (START): PRELIMINARY SAFETY EVALUATION FROM A MULTI-INSTITUTIONAL PROSPECTIVE REGISTRY

Abstract BACKGROUND Resection and intraoperative brachytherapy for operable recurrent brain metastasis allows for pathologic confirmation of recurrent disease, mass effect relief, and immediate initiation of radiotherapy (RT). In this analysis, we report patterns-of-use and treatment-related adverse events (AEs) for rBM patients treated with Cs-131 collagen tiles, an FDA-cleared intracranial brachytherapy device. METHODS Patients with rBM who underwent resection and surgically-targeted radiation therapy (GammaTile, GT Medical Technologies Inc., Tempe, AZ USA) on a prospectively enrolling phase 4 registry study (NCT04427384) were analyzed. AEs were graded per CTCAE v5.0. RESULTS Between 11/2020 and 2/2024, 56 rBM in 51 consecutive patients underwent STaRT at 19 centers, with 5 patients having 2 metastases implanted concurrently. 44 patients (86%) had prior same-site RT (median interval 14.5 mo, range 3-56). Primary tumor histologies were lung (27), melanoma (8), breast (7), renal (4), colon (2), and “other” (3). Median pre-operative maximum diameter was 3.0 cm (range 1.4-5.7); age 63 (range 28-81); 53% females; KPS median 90 (range 40-100); and median implantation time 3 minutes. 26 patients were implanted at a 1st, 15 at a 2nd, and 10 at ≥ 3rd same-site recurrence (range 1-9). At a median follow-up of 6.2 months (range &amp;lt;1-35.1), 6/51 patients (11.8%) experienced ≥Gr 3 AEs at a median of 12 (range 1-69) days postoperatively (POD). No radiation necrosis (RN) events were observed, and no AEs occurred in multi-implant cases or where STaRT was the initial form of RT. CONCLUSIONS In this prospective multi-institutional study, STaRT demonstrated an excellent safety profile in a cohort of larger rBM, even in the setting of multi-recurrent disease. Accrual and follow-up are on-going and will provide data on tumor control and long-term RN rates.

SURG-17. SALVAGE SURGERY FOR LOCAL PROGRESSION AFTER RADIATION THERAPY OF BRAIN METASTASES

Abstract Recent advances in cancer treatments have prolonged survival after the onset of brain metastases (BM), and this trend increases the risk of local progression (LP) after radiotherapy (RT)of BM. Salvage options include surgical resection, re-irradiation and medical therapies, but there is no standard management for this clinical setting. This study aimed to evaluate the outcome of salvage surgery. We performed surgical resection for intracranial metastases in 221 cases in a single institution between Apr 2014 and Mar 2024. Of those, the data of the cases underwent initial surgery after irradiation for BM were extracted. After excluding duplicated cases and those underwent surgery within one month after irradiation, we finally analyzed 49 cases. Overall survival (OS) and local progression free survival (LPFS) were evaluated by Kaplan-Meier method. All but two cases had a history of stereotactic radiosurgery/radiotherapy for BM. Histopathological diagnosis of surgical specimens was tumor recurrence in 33 cases and radiation necrosis (RN) in 16 cases. RN cases showed longer duration between radiation and LP, when comparing with recurrent cases (median 42.3. vs. 9.3 months). OS was longer in RN cases than in tumor recurrent cases (median 68.5 vs. 26.9 months). In the recurrent cases, preoperative poor KPS (under 70), active state of extracranial lesions and RPA class were associated with shorter OS. Extent of resection, postoperative chemotherapy and local irradiation did not have significant impact on OS. Twenty cases experienced local recurrence after salvage surgery, and LPFS was 7.0 months. Any of extent of removal, postoperative chemotherapy and RT were not associated with LPFS. We reported relatively long survival after salvage surgery for local failure of BM after irradiation. Salvage surgery should be considered especially in patients with good extracranial control and performance status. High recurrence rate after salvage treatment urges the development of additional treatment approaches.

ANGI-01. EXTRANEURAL METASTATIC EPENDYMOMA: DISTANT METASTASIS TO THE PLEURA, LUNGS, LYMPH NODES, AND BONE

Abstract Ependymomas are neuroepithelial tumors arising from ependymal cells surrounding the cerebral ventricles that account for 1.6-1.8% of primary CNS tumors. They rarely metastasize to extraneural structures, with one study reporting an incidence of 6.2% with a mean time from diagnosis to extraneural metastasis of 75.6 months. This spread, when it does occur, has been reported to occur to the lungs, lymph nodes, liver, and bone. We describe the case of a patient with recurrent WHO Grade III ependymoma, ZFTA::RELA fusion positive, with extraneural metastatic disease to the thoracic spine, lungs, and pelvic bones. He was treated with multiple surgical resections, radiation therapy, and salvage chemotherapy for his extraneural metastasis to the lungs, bone, pleural space, and lymph nodes. His functional and respiratory statuses declined until he ultimately developed pneumonia, status epilepticus, then spontaneous respiratory arrest, which resulted in his passing away. Salvage chemotherapy for ependymoma has unclear mortality benefit and more research must be done to determine how best to treat patients with extraneural metastases, particularly those who fail traditional treatment with resection and radiation therapy.

Multidisciplinary management strategies for recurrent brain metastasis after prior radiotherapy: An overview.

As cancer patients with intracranial metastatic disease experience increasingly prolonged survival, the diagnosis and management of recurrent brain metastasis pose significant challenges in clinical practice. Prior to deciding upon a management strategy, it is necessary to ascertain whether patients have recurrent/progressive disease vs adverse radiation effect, classify the recurrence as local or distant in the brain, evaluate the extent of intracranial disease (size, number and location of lesions, and brain metastasis velocity), the status of extracranial disease, and enumerate the interval from the last intracranially directed intervention to disease recurrence. A spectrum of salvage local treatment options includes surgery (resection and laser interstitial thermal therapy [LITT]) with or without adjuvant radiotherapy in the forms of external beam radiotherapy, intraoperative radiotherapy, or brachytherapy. Nonoperative salvage local treatments also range from single fraction and fractionated stereotactic radiosurgery (SRS/FSRS) to whole brain radiation therapy (WBRT). Optimal integration of systemic therapies, preferably with central nervous system (CNS) activity, may also require reinterrogation of brain metastasis tissue to identify actionable molecular alterations specific to intracranial progressive disease. Ultimately, the selection of the appropriate management approach necessitates a sophisticated understanding of patient, tumor, and prior treatment-related factors and is often multimodal; hence, interdisciplinary evaluation for such patients is indispensable.

Localized hepatocellular carcinoma: Is liver-directed therapy alone as efficacious as surgical resection?

ObjectiveStudies of the efficacy of nonsurgical methods of liver-directed therapy (percutaneous microwave or radiofrequency ablation, transarterial bland embolization, chemoembolization, and/or radioembolization) in the treatment of hepatocellular cancer lack contemporaneous comparative surgical cohorts. The role of these methods of liver-directed therapy as destination treatment in hepatocellular cancer is not well defined. MethodsWe queried our institutional registry for patients undergoing resection or liver-directed therapy alone for clinical stage I to IVa hepatocellular cancer between 2012 and 2022. Multivariable regression and Cox modeling were used to identify factors associated with resection and all-cause mortality. Patients undergoing resection were 1:3 propensity matched for age, Mayo End-Stage Liver Disease score and clinical stage to those undergoing liver-directed therapy. Kaplan-Meier methods were used to compare 5-year disease-specific and overall survival for matched cohorts. ResultsThree hundred thirty patients met inclusion criteria; 45 underwent resection, and 285 liver-directed therapy. On multivariable regression, factors associated with resection included age (adjusted odds ratio: 0.96, P = .007) and Mayo End-Stage Liver Disease score (adjusted odds ratio: 0.92, P = .033). On Cox modeling, factors associated with mortality-risk included Mayo End-Stage Liver Disease score (adjusted hazards ratio: 1.03, P = .01), advanced clinical stage (stage III adjusted hazards ratio: 1.9, P = .002), and resection (adjusted hazards ratio: 0.43, P = .001). Forty-five patients undergoing resection were matched to 135 undergoing liver-directed therapy. On Kaplan-Meier comparison of matched cohorts, patients undergoing resection demonstrated improved overall survival (38.1 vs 8.4%, P = .015) but disease-specific survival similar to that for those undergoing liver-directed therapy (84.0 vs 74.0%, P = .095). ConclusionLiver-directed therapy is effective as treatment for patients with localized hepatocellular cancer providing disease-specific survival similar to that provided by surgical resection.

Comparison of Prognostic Outcomes Between Repeat Liver Resection and Particle Therapy for Patients with Recurrent Hepatocellular Carcinoma.

Particle therapy (PT) as an initial hepatocellular carcinoma (HCC) treatment has been reported to be effective; however, its efficacy for the treatment of recurrent HCC remains unclear. This study aimed to evaluate the efficacy of PT compared with repeat liver resection for treating recurrent HCC after initial LR, with a focus on prognostic outcomes. Between 2005 and 2019, 89 and 49 patients underwent repeat LR and PT for recurrent HCC after initial LR, respectively. The 5-year overall survival (OS) and recurrence-free survival (RFS) were evaluated using propensity score matching. Treatment-related complications were scored using the National Institute Common Terminology Criteria for Adverse Events (CTCAE) and were compared between the repeat LR and PT groups. In the entire cohort, the 5-year OS was significantly better in the repeat LR group than in the PT group (75% vs. 48%; p=0.0003), and the 5-year RFS was comparable in both groups (22% vs. 13%; p=0.088). Propensity score matching created 34 pairs of patients; no significant differences in the 5-year OS (65% vs. 48%; p=0.310) and RFS (21% vs. 8%; p=0.271) were observed between the repeat LR and PT groups. The proportion of CTCAE grade ≥3 complications was 8.8% and 5.9% in the repeat LR and PT groups, respectively (p=0.641). After initial LR, the prognosis and treatment-related complications in patients with recurrent HCC were comparable between the repeat LR and PT groups in the matched cohort; therefore, PT may remain one of the multidisciplinary treatment options for recurrent HCC.

Combination Resective or Ablative Epilepsy Surgery with Neurostimulation for Complex Epilepsy Networks: A Case Series

Introduction: Complex epilepsy networks with multifocal onset zones that overlap with eloquent cortex may benefit from combined surgical approaches. However, limited data exist on outcomes associated with performing these therapies in tandem. In this case series, we report on 6 patients who underwent combination surgery with either resection or laser interstitial thermal therapy (LITT) and neuromodulation with responsive neurostimulation (RNS) or deep brain stimulation (DBS). Methods: We performed a retrospective review of adult patients with medically refractory epilepsy who underwent staged combination epilepsy surgeries during the same admission at our institution. Six cases treated between 2019 and 2023 were identified. All patients underwent a presurgical work-up including invasive intracranial monitoring and underwent a combined approach with either surgical resection, LITT, RNS, or DBS. We extracted data on demographic, clinical, and surgical characteristics. The primary outcome was change in seizure frequency from baseline. Results: The mean age was 42.7 years old (4 female). All patients had at least one epileptogenic zone in the temporal lobe, two in extratemporal neocortex, two in periventricular nodular heterotopia. For the staged combination approach, 3 patients underwent LITT followed by RNS, two underwent resection and RNS, and one received LITT and DBS. The mean reduction in seizure frequency per month at last follow-up was 90%. Postoperatively, 1 patient experienced superior visual field deficits related to LITT, and another had postoperative deep vein thrombosis. Conclusion: All patients experienced at least an 83% reduction in seizures. This case series demonstrates the potential benefits of a combined surgical approach in patients with multifocal seizures and at least one lesion that can be safely resected or ablated. Future prospective studies are warranted.

Research progresses of imaging studies on preoperative prediction of microvascular invasion of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the predominant form of primary liver cancer, accounting for approximately 90% of liver cancer cases. It currently ranks as the fifth most prevalent cancer worldwide and represents the third leading cause of cancer-related mortality. As a malignant disease with surgical resection and ablative therapy being the sole curative options available, it is disheartening that most HCC patients who undergo liver resection experience relapse within five years. Microvascular invasion (MVI), defined as the presence of micrometastatic HCC emboli within liver vessels, serves as an important histopathological feature and indicative factor for both disease-free survival and overall survival in HCC patients. Therefore, achieving accurate preoperative noninvasive prediction of MVI holds vital significance in selecting appropriate clinical treatments and improving patient prognosis. Currently, there are no universally recognized criteria for preoperative diagnosis of MVI in clinical practice. Consequently, extensive research efforts have been directed towards preoperative imaging prediction of MVI to address this problem and the relative research progresses were reviewed in this article to summarize its current limitations and future research prospects.

Red herrings and zebras and TB, oh my! Unexpected bone marrow presentation of Mycobacterium tuberculosis

Abstract Introduction/Objective Epithelioid granulomas are uncommon and non-specific findings in bone marrow samples, and should prompt additional testing for appropriate diagnosis and treatment, especially in the immunocompromised patient. The differential diagnosis for bone marrow granulomas includes infections, neoplasia, autoimmune disease, sarcoidosis, and drug/therapy reaction. Although bone marrow workup to delineate the cause of granulomas should include staining to rule out both infection and lymphoma, morphologic review is often inconclusive. Final diagnosis requires clinical consultation and additional testing. Methods/Case Report A 76-year-old male was admitted to the hospital from the emergency department for a level 2 trauma after being found on the ground ~3 hours after a fall. The patient reported a recent increasing frequency of falls with associated weakness, as well as an almost 30 lb weight loss over the last 3.5 months and low grade fevers over several weeks. His past medical history was significant for treatment for urothelial carcinoma with transurethral resection and BCG therapy, hypertension, coronary artery disease, and peripheral vascular disease. Imaging showed hepatosplenomgaly, suspicious for early cirrhosis, and mild peripancreatic lymphadenopathy. Initial laboratory abnormalities demonstrated mild anemia, low albumin, and mild increase in ALT, AST, and alkaline phosphotase. Initial Infectious Diseases workup was negative for causative etiology (blood cultures, tick-borne parasites, and respiratory pathogens). Patient symptoms did not improve and cytopenias worsened. A bone marrow biopsy showed multiple non-necrotizing epithelioid granulomas. Despite low clinical concern for infectious etiology, mycobacteria blood culture isolated Mycobacterium tuberculosis complex. Final results were available 112 days after specimen collection. Results (if a Case Study enter NA) NA Conclusion Although tuberculosis is commonly associated with granulomatous pathology, infection is very uncommon in North American patients who have not traveled and alternative diagnoses might initially be favored. A high suspicion for mycobacterial infections is essential for diagnosis even in low-incidence populations with no known exposure or risk factor(s).

Analysis of clinical features, treatment methods, and prognostic influence factors in patients with malignant peripheral nerve sheath tumor

To investigate the clinical features, treatment methods, and prognostic influence factors of patients with malignant peripheral nerve sheath tumor (MPNST). A retrospective analysis was conducted on 96 MPNST patients treated between January 1, 2015 and December 31, 2021. There were 46 males and 50 females, aged between 15 and 87 years (mean, 48.2 years). The tumors were located in the trunk in 50 cases, extremities in 39 cases, and head and neck in 7 cases. The maximum tumor diameter was <5 cm in 49 cases, ≥5 cm in 32 cases, with 15 cases missing data. Tumor depth was deep in 77 cases and superficial in 19 cases. The Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) histological grading was G1 in 9 cases, G2 in 12 cases, and G3 in 34 cases, with 41 cases missing data. There were 37 recurrent MPNST cases, 32 cases with neurofibromatosis type 1 (NF1), and 26 cases in stage Ⅳ. Postoperative adjuvant radiotherapy was administered to 25 patients, perioperative chemotherapy to 45 patients, and anlotinib-targeted therapy to 30 patients. R 0 resection was achieved in 73 cases. Patients were divided into groups based on the presence or absence of NF1, and baseline data between the two groups were compared. Kaplan-Meier curves were generated to assess disease-free survival (DFS) and overall survival (OS) based on various factors (age, gender, presence of NF1, recurrent MPNST, stage Ⅳ MPNST, FNCLCC grade, R 0 resection, tumor location, tumor size, tumor depth, perioperative chemotherapy, postoperative adjuvant radiotherapy, and anlotinib-targeted therapy), and differences between survival curves were analyzed using the Log-Rank test. Multivariate COX proportional hazards regression was used to identify independent prognostic factors for MPNST. Patients with NF1 had a significantly higher proportion of superficial tumors and lower FNCLCC grade compared to those without NF1 ( P<0.05); no significant difference was found for other variables ( P<0.05). Kaplan-Meier analysis showed that recurrent MPNST, stage Ⅳ MPNST, FNCLCC grade, R 0 resection, perioperative chemotherapy, and anlotinib-targeted therapy were factors influencing 1-year DFS ( P<0.05), while stage Ⅳ MPNST, FNCLCC grade, and perioperative chemotherapy were factors affecting 3-year OS ( P<0.05). Multivariate COX proportional hazards regression analysis revealed that recurrent MPNST and high-grade FNCLCC (G3) were independent prognostic factors for 1-year DFS ( P<0.05), while stage Ⅳ MPNST, superficial tumor depth, age over 60 years, postoperative adjuvant radiotherapy, and anlotinib-targeted therapy were independent prognostic factors for 3-year OS ( P<0.05). MPNST patients with NF1 tend to have more superficial tumors and lower FNCLCC grades. FNCLCC grade, R 0 resection, and adjuvant therapies, including radiotherapy and anlotinib-targeted therapy, are closely associated with MPNST prognosis. Complete surgical resection should be prioritized in clinical management, along with adjuvant treatments such as radiotherapy and targeted therapy of anlotinib to improve patient outcomes.