Epstein-Barr virus-associated post-transplant smooth muscle tumours in a kidney transplant patient.

We report on a 14-year-old girl who developed post-transplantation smooth muscle tumours (PTSMT) located in the spleen, lungs, liver, and central nervous system (CNS), 4 years after kidney transplantation. She was asymptomatic, and the disease was detected during the work-up for a urinary tract infection. Diagnosis was performed by the analysis of a tissue specimen, through the biopsy of a lung tumour, which revealed a proliferation of spindle-shaped cells which were positive for actin and vimentin. In situ hybridization studies were positive for Epstein-Barr virus, and her serologic status was negative prior to transplantation. We reduced immunosuppression by stopping mycophenolate and switching tacrolimus for sirolimus. After 18 months of follow-up, she remains asymptomatic, and the CNS tumour reduced its diameter from 24 × 21 mm to 14 × 13 mm. PTSMT should be considered in the differential diagnosis of transplanted patients who develop neoplastic complications associated with immunosuppression.

Lactating Adenoma Arising From Ovarian Mature Teratoma: An Unusual Presentation of a Young Pregnant Woman.

Mature teratoma is a benign germ cell tumor, histologically comprising components from mesoderm, ectoderm, and endoderm layer tissue. Here, we report a rare case of lactating adenoma arising from mature teratoma of the ovary in a pregnant female. To the best of our knowledge, only four cases of lactating adenoma arising from ovarian teratoma have been reported in the literature so far. This case is the fifth case reported worldwide, and the first case report with dual rare findings - choroidal plexus and lactating adenoma of mammary tissue in benign mature cystic teratoma. This is the second case report which uses immunohistochemical (IHC) markers to confirm the diagnosis. Grossly, the cystic structure was measuring 10x7x5cm. The cut surface revealed mixed solid and cystic areas filled with pultaceous material admixed with hair. Microscopy showed an ovarian cyst lined by stratified squamous epithelium with underlying sebaceous glands, apocrine acini, fatty tissue, smooth muscle, and glial tissues. Also noted mammary tissue composed of proliferating hyperplastic acini with central dilated ducts filled with eosinophilic secretions arranged in lobules. Immunohistochemistry with estrogen receptor (ER) and progesterone receptor (PR) showed luminal and ductal positivity. Strong expression of IHC markers such as p63 and pan-cytokeratin (pan-CK) was noted in myoepithelial cells and luminal cells respectively. Thus, confirming it as mammary tissue with hyperplastic ducts and acini.

Membrane-coated nanoparticles as a biomimetic targeted delivery system for tumour therapy.

Drug therapy towards tumours often causes adverse effects because of their non-specific nature. Membrane-coated technology and membrane-coated nanoparticles provide an advanced and promising platform of targeted and safe delivery. By camouflaging the nanoparticles with natural derived or artificially modified cell membranes, the nano-payloads are bestowed with properties from cell membranes such as longer circulation, tumour or inflammation-targeting, immune stimulation, augmenting the performance of traditional therapeutics. In this review, we review the development of membrane coating technology, and summarise the technical details, physicochemical properties, and research status of membrane-coated nanoparticles from different sources in tumour treatment. Finally, we also look forward to the prospects and challenges of transforming membrane coating technology from experiment into clinical use. Taken together, membrane-coated nanoparticles are bound to become one of the most potential anti-tumour strategies in the future.

Impact of high rheumatoid factor levels on treatment outcomes with certolizumab pegol and adalimumab in patients with rheumatoid arthritis.

OBJECTIVE: To assess the impact of baseline rheumatoid factor (RF) level on drug concentrations and efficacy of certolizumab pegol (CZP; tumour necrosis factor inhibitor [TNFi] without a crystallisable fragment [Fc]) and adalimumab (ADA; Fc-containing TNFi) in patients with rheumatoid arthritis (RA). METHODS: The phase 4 EXXELERATE study (NCT01500278) was a 104-week, randomised, single-blind (double-blind until week 12; investigator-blind thereafter), head-to-head study of CZP vs ADA in patients with RA. In this post hoc analysis, we report drug concentration and efficacy outcomes stratified by baseline RF quartile (≤Q3 or >Q3). RESULTS: Baseline data by RF quartiles were available for 453 CZP-randomised and 454 ADA-randomised patients (≤Q3: ≤204 IU/ml; >Q3: >204 IU/ml). From week 12, the area under the curve (AUC) of ADA concentration was lower in patients with RF > 204 IU/ml vs patients with RF ≤ 204 IU/ml; the AUC of CZP concentration was similar in patients with RF ≤ 204 IU/ml and >204 IU/ml. For patients with RF ≤ 204 IU/ml, disease activity score (DAS28)-C-reactive protein (CRP) was similar between CZP- and ADA-treated patients through week 104. For patients with RF > 204 IU/ml, mean DAS28-CRP was lower in CZP- vs ADA-treated patients at week 104. The proportion of patients with RF > 204 IU/ml achieving DAS28-CRP low disease activity at week 104 was greater in CZP- vs ADA-treated patients. CONCLUSION: CZP was associated with maintained drug concentration and efficacy in patients with RA and high RF and may therefore be a more suitable therapeutic option than TNFis with an Fc fragment in these patients.

MAML3-fusions modulate vascular and immune tumour microenvironment and confer high metastatic risk in pheochromocytoma and paraganglioma.

Pheochromocytomas and paragangliomas are rare neuroendocrine tumours. Around 20-25 % of patients develop metastases, for which there is an urgent need of prognostic markers and therapeutic stratification strategies. The presence of a MAML3-fusion is associated with increased metastatic risk, but neither the processes underlying disease progression, nor targetable vulnerabilities have been addressed. We have compiled a cohort of 850 patients, which has shown a 3.65 % fusion prevalence and represents the largest MAML3-positive series reported to date. While MAML3-fusions mainly cause single pheochromocytomas, we also observed somatic post-zygotic events, resulting in multiple tumours in the same patient. MAML3-tumours show increased expression of neuroendocrine-to-mesenchymal transition markers, MYC-targets, and angiogenesis-related genes, leading to a distinct tumour microenvironment with unique vascular and immune profiles. Importantly, our findings have identified MAML3-tumours specific vulnerabilities beyond Wnt-pathway dysregulation, such as a rich vascular network, and overexpression of PD-L1 and CD40, suggesting potential therapeutic targets.

Investigation of the Expression and Regulation of SCG5 in the Context of the Chromogranin-Secretogranin Family in Malignant Tumors.

The SCG5 gene has been demonstrated to play an essential role in the development and progression of a range of malignant neoplasms. The regulation of SCG5 expression involves multiple biological pathways. According to relevant studies, SCG5 is differentially expressed in different cancers, and its up- or down-regulation may even affect tumour growth, invasion, and migration, which caught our attention. Therefore, we summarise the regulatory roles played by the SCG5 gene in a variety of cancers and the biological regulatory mechanisms associated with its possible promotion or inhibition of tumour biological behavior, to further explore the potential of SCG5 as a new tumour marker and hopefully provide theoretical guidance for subsequent disease research and treatment.

Radiation-induced angiosarcoma of the breast: A case report.

INTRODUCTION AND IMPORTANCE: Today, breast-conserving surgery (BCS) and adjuvant radiotherapy are preferred treatments for patients with early invasive breast cancer. Radiation-induced angiosarcoma (RIAS) of the breast is a rare but serious complication of radiotherapy. CASE PRESENTATION: Seventy-one-year-old woman is presented to our department with a locally advanced dark red polypoid lesion on her left breast. She had left BCS, axillary dissection, and adjuvant radiotherapy for invasive breast cancer 8 years before presentation. A small tissue sample from the breast lesions was sent for histopathologic examination that the diagnosis was angiosarcoma of the breast. She had neoadjuvant chemotherapy. Following the completion of chemotherapy, a total mastectomy was performed as surgical treatment. The final histopathologic diagnosis was well-differentiated angiosarcoma. CLINICAL DISCUSSION: RIAS of the breast is rare disease that develops after a several-year latency period. Locally advanced disease was initially treated with neoadjuvant chemotherapy which appears to be effective for significant disease regression. Patients who respond well to chemotherapy in vivo may have higher disease-specific survival rates. After chemotherapy-induced regression of locally advanced sarcoma, total mastectomy was performed for radical treatment. CONCLUSION: RIAS of the breast is defined as the histological diagnosis of angiosarcoma in an irradiated region after a long latency period in a patient who has previously received radiotherapy for breast carcinoma. Based on clinical and nuclear imaging data, we may conclude that neoadjuvant chemotherapy can result in significant disease regression, and following neoadjuvant chemotherapy the treatment of angiosarcoma is completed by radical breast surgery.

Preoperative thromboelastography parameters in predicting the tumour stage of oral squamous cell carcinoma.

BACKGROUND: A variety of solid tumours, including oral squamous cell carcinoma (OSCC), can cause coagulation abnormalities, and this phenomenon is known as tumour-associated hypercoagulation. We aimed to explore the preoperative thromboelastography (TEG) parameter profiles of OSCC patients, and to investigate their trends in relation to tumour stage progression, and to evaluate their value for predicting cervical lymph node metastasis. METHODS: Data on thromboelastographic parameters and conventional coagulation indices were retrospectively collected, and comparisons were performed among preoperative primary OSCC patients (n = 311), recurrent/metastatic OSCC patients (n = 44) and a control group (n = 71). Among primary OSCC patients, the correlation with tumour stage and the predictive role of cervical lymph node metastasis were analyzed. RESULTS: Hypercoagulability occurred in OSCC patients and tended to become more pronounced as the tumour progressed. The whole-time phase of coagulation increased with increasing T stage, while the early phase of coagulation increased with increasing N stage. CONCLUSIONS: Preoperative TEG parameters are closely related to tumour stage and progression, suggesting that TEG can be used as an important indicator for predicting tumour stage and as a potential biomarker.

Protocol: revolutionizing central nervous system tumour diagnosis in low- and middle-income countries: an innovative observational study on intraoperative smear and deep learning.

OBJECTIVE: The aim of this study is to assess the feasibility and implementation of a novel approach for intraoperative brain smears within the operating room, which is augmented with deep learning technology. Materials and methods: This study is designed as an observational to evaluate the feasibility and implementation of using an innovative approach to intraoperative brain smears within the operating room, augmented with deep learning technology. The study will be conducted at Aga Khan University Hospital in Karachi, Pakistan, from May 2024 to July 2026, with an estimated sample size of 258. A neurosurgical trainee, trained by the study neuropathologist, will prepare and examine the smears under a microscope in the operating room. The findings of the trainee will be documented and compared to routine intraoperative consultations (smear and/or frozen section) and final histopathology results obtained from the pathology department. Additionally, the study will incorporate artificial intelligence tools to assist with the interpretation of smear and a telepathology interface to enable consultation from an off-site neuropathologist. CONCLUSIONS: The results of this study will hold significant potential to revolutionise neurosurgery practices in lowand middle-income countries by introducing a cost-effective, efficient, and high-quality intraoperative consultation method to settings that currently lack the necessary infrastructure and expertise. The implementation of this innovative approach has the potential to improve patient outcomes and increase access to intraoperative diagnosis, thereby addressing a significant unmet need in LMICs.

Serum liquid biopsy for brain tumours: a scoping analysis of practicable approaches in low- and middle-income countries.

Approaches to brain tumour diagnosis and detecting recurrence after treatment are costly and significantly invasive. Developing peripheral-sample liquid biopsy tools is the key to enhancing our ability to prognosticate brain tumour subtypes and molecular heterogeneity. The present scoping review was designed to discuss current updates in liquid biopsy tools for diagnosis and guiding clinical management of brain tumours; we evaluated the literature within the context of low-and-middle-income country challenges. Circulating tumour cells (CTCs), circulating tumour DNA (ctDNA), cell-free DNA (cfDNA), extracellular vesicle-associated biomarkers, protein biomarkers, microRNAs, and serum metabolites are discussed with the collation of current data supporting their utility in liquid biopsy. Further challenges to implanting liquid biopsy tools at a systematic level are highlighted.

Developing neuro-oncology clinical trials in low- and middle-income countries: a scoping review of the current literature.

Low- and middle-income countries (LMICs) have historically been under-represented in clinical trials, leading to a disparity in evidence-based recommendations for the management of neurooncological conditions. To address this knowledge gap, we conducted a scoping review to assess the current literature on clinical trials in neuro-oncology from LMICs. The eligibility criteria for inclusion in this review included clinical trials registered and conducted with human subjects, with available English language text or translation, and focussed on neuro-oncological cases. The literature search strategy captured 408 articles, of which 61 met these criteria, with a significant number of randomised controlled trials from specific LMICs. The review found that LMIC clinical trials have contributed significantly to understanding surgical, chemotherapeutic, and radiation therapy interventions for brain tumours, paediatric cancers, and the repurposing of drugs as new targets in neuro-oncology. These findings highlight the potential for expanding clinical trials research in neuro-oncology in LMICs, which may significantly impact global understanding and management of these conditions, particularly from diverse populations from the global south.

Consensus guidelines for the management of adult high-grade gliomas for low and middle-income countries.

High-grade glioma (HGG), a formidable and often incurable disease, presents an even greater challenge in low- and middle-income countries (LMICs) where resources and medical expertise are scarce. This scarcity not only exacerbates the suffering of patients but also contributes to poorer clinical outcomes. Particularly in LMICs, the underrepresentation of the population in clinical trials and the additional hurdles posed by financial constraints underscore an urgent need for contextspecific management strategies. In response, we have rigorously evaluated recent guidelines from leading medical societies, adapting them to suit the specific needs and limitations of the local context in Pakistan. This effort, undertaken in collaboration with local physicians, aims to provide a comprehensive, standardised approach to diagnose, treat, and follow-up with HGG patients. By focussing on the best available clinical evidence and judicious use of limited resources, we strive to improve patient care and outcomes in these challenging settings.

Consensus guidelines for the management of posterior fossa tumour for low- and middle-income countries.

The posterior fossa is a limited compartment therefore lesions compressing its structures can result in devastating outcomes. It can cause significant neurological deficit due to mass effect on critical structures and hydrocephalus. Due to the nature of the infratentorial region, urgent surgical intervention is often the first-line option. Surgical neuro-oncologists guide patients and caregivers through the course of this disease and to inform them about the various options for management and long-term outcome optimisation. There is currently conflicting data; however, institutional experiences can guide us towards achieving improvements in surgical outcomes and quality of life. Advances in molecular classifications coupled with highdose radiation treatment improve our capacity for improving overall survival in these patients. Common childhood tumours are ependymomas, medulloblastomas, and juvenile pilocytic astrocytomas, while adults often present with metastases, and less commonly, cerebellar haemangioblastomas and gliomas. This paper outlines management strategies with consideration for multidisciplinary care and resourcelimited settings.

Consensus guidelines for the management of primary supra-tentorial intraventricular tumour for low- and middle-income countries.

Almost any primary or metastatic brain tumour can manifest in intraventricular (IV) locations. These tumours may either originate within the ventricular system or extend into the IV space through growth. Such neoplasms represent a broad spectrum, with supratentorial IV tumours forming a heterogeneous group. This group includes primary ependymal tumours, central neurocytomas, choroid plexus tumours, and notably, meningiomas, as well as a variety of non-neoplastic, benign, glial, and metastatic lesions that can secondarily invade the IV compartment. Often presenting with nonspecific symptoms, these tumours can lead to delayed medical attention. The diversity in potential diagnoses, combined with their deep and complex locations, poses significant management challenges. This paper aims to delineate optimal management strategies, underscoring the importance of multidisciplinary care, especially in settings with limited resources, to effectively navigate the complexities associated with treating intraventricular brain tumours.

Judicious and evidence-based use of radiosurgery - recommendations for low-middle income countries.

Surgical removal remains the primary treatment for most brain tumours. However, radiosurgery presents an effective, less invasive alternative or additional treatment for certain types. Our goal was to explore radiosurgery's roles in treating various brain tumours, focussing on its application in low- and middle-income countries (LMICs). We reviewed all relevant systematic reviews, metaanalyses, and guidelines to determine the most effective radiosurgical approaches. Additionally, we consulted a panel of experts with over ten years of experience in LMICs, such as Pakistan. For brain tumours, stereotactic radiosurgery should generally follow a confirmed histopathological diagnosis. Exceptions include tumours identified through Magnetic Resonance Imaging (MRI), like Vestibular Schwannoma (VS), pre-diagnosed Neurofibromatosis type 2 (NF2), multiple typical meningiomas, and metastases with a known histology from another site. While radiosurgery is gaining traction as a primary and adjunct treatment in some LMICs, the lack of regional guidelines, trained personnel, and collaboration among specialists hinders its wider adoption. Addressing these gaps is crucial for expanding radiosurgical care in these regions.

Phenotypic and spatial heterogeneity of CD8+ tumour infiltrating lymphocytes.

CD8+ T cells are the workhorses executing adaptive anti-tumour response, and targets of various cancer immunotherapies. Latest advances have unearthed the sheer heterogeneity of CD8+ tumour infiltrating lymphocytes, and made it increasingly clear that the bulk of the endogenous and therapeutically induced tumour-suppressive momentum hinges on a particular selection of CD8+ T cells with advantageous attributes, namely the memory and stem-like exhausted subsets. A scrutiny of the contemporary perception of CD8+ T cells in cancer and the subgroups of interest along with the factors arbitrating their infiltration contextures, presented herein, may serve as the groundwork for future endeavours to probe further into the regulatory networks underlying their differentiation and migration, and optimise T cell-based immunotherapies accordingly.

Long-term TNF-alpha therapy for preserving beta cell function in new onset type 1 diabetes: a case report.

BACKGROUND: Type 1 diabetes mellitus (T1D) is an autoimmune disease caused by destruction of pancreatic islet beta-cells. There is significant residual beta-cell function, measured through circulating C-peptide, present at the time of T1D diagnosis but this subsequently decreases with time. Higher residual beta-cell function at diagnosis associates with better glycaemic control and less glucose variability, and later in the disease course with less hypoglycaemia, lower glucose variability and fewer microvascular complications. There is therefore value in preserving residual beta cell function in new onset T1D Immunotherapeutic agents can protect residual beta-cell function in type 1 diabetes. However, clinical trials of such agents, whilst demonstrating C-peptide preservation in short term studies, have yet to be taken forward into routine clinical care due to concerns around safety and long-term efficacy. Here we report the case of a gentleman with newly diagnosed T1D whose glycaemic control and insulin requirement improved whilst on a five year infusion programme of infliximab, a monoclonal antibody against TNF-alpha, for colitis. CASE PRESENTATION: A 52-year-old White Caucasian man was diagnosed with T1D in August 2018. Glucose was 25.6 mmol/L, HbA1c was 98mmol/mol and GAD antibodies were strongly positive. HbA1c marginally improved to 91mmol/mol following initiation of insulin detemir 5 units at night and 1:10 g of insulin aspart (November 2018). In June 2019, he developed rectal bleeding and abdominal pain. Following colonoscopy, he was diagnosed with "indeterminate colitis" and commenced on 6-weekly infusions of 400-450 mg infliximab. Thus far, he has received 32 doses and achieved colitis remission. Following infliximab initiation there was increased frequency of mild-moderate hypoglycaemia and he was gradually weaned off and discontinued detemir in June 2020. Since then, HbA1c improved from 57mmol/mol in August 2019 to 52mmol/mol in April 2022, remaining stable at 51mmol/mol. His most recent HbA1c is 54mmol/mol in February 2024. His c-peptide was 550pmol/L in October 2022 and 442pmol/L in February 2024, suggesting well-preserved beta-cell function almost 6 years post-diagnosis. CONCLUSIONS: Our patient's improvement in glycaemic control can be explained by immunomodulation and C peptide preservation from infliximab. With the growing focus on type 1 diabetes disease modulation and working towards an 'insulin free T1D', our findings strengthen the evidence base for the repurposing of and long-term treatment with anti-TNF-α agents to preserve beta-cell function in new onset T1D.

Challenging Nasal Pathologies: An Inverted Nasal Papilloma Case Series Illustrating Diagnostic Challenges and Management Strategies.

The sinonasal inverted papilloma is a benign tumor located in the sinuses lining the nasal cavity. It is a very rare tumor, representing approximately 4% of all sinonasal tumors. The incidence of sinonasal inverted papilloma is higher in males than females and is most commonly diagnosed in the 5th decade of life. Four separate cases of sinonasal pathology involving inverted papillomas are presented in this case series. The first clinical case presents a 68-year-old man with persistent nasal symptoms, who was found to have a sinonasal papilloma, which was successfully removed surgically. In the second case, a 61-year-old woman needed multiple procedures for a comprehensive surgical approach due to her inverted papilloma. Despite postoperative complications, the patient showed improvement at later follow-up appointments. In the third case, a 65-year-old man who had an inverted nasal papilloma previously needed surgery to remove and clear the tumor after developing acute sinusitis and rhinosinusitis symptoms. Last but not least, a 57-year-old male presented with nasal blockage and purulent discharge. Polyps were observed during the examination. The initial biopsy indicated the presence of chronic inflammatory polyps. However, during the operation, a first sample biopsy revealed an inflammatory polyp, but due to the appearance of the mass, the surgeon became suspicious and decided to take another biopsy. The second biopsy confirmed the presence of an inverted nasal papilloma. All things considered, these cases demonstrate clinical variability, difficulties in diagnosing, and effective management techniques related to inverted and sinonasal papillomas. The aim of this case series is to emphasize the importance of proper history taking, physical examination, and use of diagnostic tools to distinctly diagnose inverted nasal papilloma as its symptoms are similar to rhinosinusitis, especially chronic rhinosinusitis.

Understanding the role of miRNAs in cervical cancer pathogenesis and therapeutic responses.

Cervical cancer (CC) is the most common cancer in women and poses a serious threat to health. Despite familiarity with the factors affecting its etiology, initiation, progression, treatment strategies, and even resistance to therapy, it is considered a significant problem for women. However, several factors have greatly affected the previous aspects of CC progression and treatment in recent decades. miRNAs are short non-coding RNA sequences that regulate gene expression by inhibiting translation of the target mRNA. miRNAs play a crucial role in CC pathogenesis by promoting cancer stem cell (CSC) proliferation, postponing apoptosis, continuing the cell cycle, and promoting invasion, angiogenesis, and metastasis. Similarly, miRNAs influence important CC-related molecular pathways, such as the PI3K/AKT/mTOR signaling pathway, Wnt/ß-catenin system, JAK/STAT signaling pathway, and MAPK signaling pathway. Moreover, miRNAs affect the response of CC patients to chemotherapy and radiotherapy. Consequently, this review aims to provide an acquainted summary of onco miRNAs and tumor suppressor (TS) miRNAs and their potential role in CC pathogenesis and therapy responses by focusing on the molecular pathways that drive them.

Differences in mutations across tumour sizes in clear-cell renal cell carcinoma.

OBJECTIVE: To assess the distribution of key mutations across tumour sizes in clear-cell renal cell carcinoma (ccRCC), and secondarily to examine the prognostic impact of aggressive mutations in smaller ccRCCs. PATIENT AND METHODS: The distribution of mutations (VHL, PBRM1, SETD2, BAP1 and CDKN2A loss) across tumour sizes was assessed in 1039 ccRCCs treated with nephrectomy in cohorts obtained from the Tracking Cancer Evolution (TRACERx), The Cancer Genome Atlas (TCGA) and the Cancer Genomics of the Kidney (CAGEKID) projects. Logistic regression was used to model the presence of each mutation against size. In our secondary analysis, we assessed a subset of ccRCCs ≤7 cm for associations of key aggressive mutations (SETD2, BAP1, and CDKN2A loss) with metastasis, invasive disease and overall survival, while controlling for size. A subset of localised tumours ≤7 cm was also used to assess associations with recurrence after nephrectomy. RESULTS: On logistic regression, each 1-cm increase in tumour size was associated with aggressive mutations, SETD2, BAP1, and CDKN2A loss, at odds ratios (ORs) of 1.09, 1.10 and 1.19 (P < 0.001), whereas no significant association was observed between tumour size and PBRM1 (OR 1.02; P = 0.23). VHL was mildly negatively associated with a 1-cm increase in size (OR 0.95; P = 0.01). Among tumours ≤7 cm, SETD2 and CDKN2A loss were associated with metastatic disease at ORs of 3.86 and 3.84 (P < 0.05) while controlling for tumour size. CDKN2A loss was associated with worse overall survival, with a hazard ratio (HR) of 2.19 (P = 0.03). Among localised tumours ≤7 cm, SETD2 was associated with worse recurrence-free survival (HR 2.00; P = 0.03). CONCLUSION: Large and small ccRCCs are genomically different. Aggressive mutations, namely, SETD2, BAP1, and CDKN2A loss, are rarely observed in small ccRCCs and are observed more frequently in larger tumours. However, when present in tumours ≤7 cm, SETD2 mutations and CDKN2A loss were still independently associated with invasive disease, metastasis, worse survival, and recurrence after resection, after controlling for size.