Symptomatic Tumor Research Articles

LGG-38. Dose-dependent seizure control for an NF1 patient treated via MEK-inhibition for optic pathway glioma

BACKGROUND: Low-grade gliomas (LGG) are the most common solid tumor of childhood and can result in neurologic complications, including seizures, focal neurologic deficits, and learning difficulties. Molecularly targeted agents are increasingly being utilized to treat LGG, but the effect of these agents on accompanying neurologic complications are poorly understood. CASE: An 8-years old male with Neurofibromatosis Type 1 (NF1), medically refractory epilepsy and deep extensive glioma (extending from the optic pathway and involving the basal ganglia and corpus collosum) began selumetinib therapy due to radiographic and symptomatic tumor progression. Radiographic response (resolution of enhancement) was observed at 12 weeks of therapy, accompanied by improvement in seizure frequency, hemiparesis, and academic performance. Due to cardiotoxicity observed at that time (asymptomatic decreased ejection fraction and shortening fraction on echocardiogram), selumetinib was reduced to 50% dosing. On this reduced dose of selumetinib, seizures increased in frequency with subsequent worsening hemiparesis and recurrence of learning difficulties. One month later, dosing was escalated back to 100% due to interval resolution of cardiotoxicity, resulting in resolution of seizures and improvement in focal neurologic deficits and cognition. DISCUSSION: Dose-dependent response to MEK inhibition was observed without concurrent changes in anti-epileptic medications. The tumor was stable in size despite improved enhancement with treatment, suggesting that objective response by RANO criteria is not necessary for improved seizure control in LGG. Recent work has implicated the RAS/MEK/ERK pathway in neuronal precursor cells as a cause for epilepsy, suggesting that MEK inhibition of NF1-heterozygous neurons could be contributing to treatment response in this patient. Improvements in weakness and academic performance may have been due to improved seizure control or a direct effect of MEK inhibition on NF1-heterozygous neurons. CONCLUSION: MEK inhibition may have a clinically relevant anti-seizure effect for patients with pediatric LGG or NF1.

Abstract P1-17-07: Consequences of stopping a 4/6 cyclin D-dependent kinase Inhibitor in metastatic breast cancer patients with clinical benefit on endocrine treatment, in the context of the COVID-19 outbreak

Abstract Background: The impact of some medical decisions hurriedly taken during the COVID-19 first wave remains unknown. We tried to assess the consequences of one of these precautionary measures, namely the interruption of a 4/6 cyclin D-dependent kinase inhibitor (CDK4/6i) in metastatic patients with clinical benefit (complete response/partial response and patients with stable disease for at least 6 months) on endocrine treatment (ET). The main reason for this interruption was to limit the risk of myelosuppression (assumed as a serious risk factor for COVID-19) and other adverse effects that could overlap with symptoms and clinical signs described in the SARS-CoV-2 infection. Methods: We included 60 patients (median age: 64 years old) in whom the CDK4/6i was stopped during the first COVID-19 outbreak. It was a non-interventional, retrospective, multicentric study. A univariate analysis was performed to assess risk factors associated with disease progression: odds ratios (OR) were estimated along with their confidence intervals (CI). Key patient characteristics, all included in the statistical model, are presented in Table 1. Results: The average duration of a CDK4/6i interruption was 8 weeks. During this therapeutic break, 22 (37 %) patients had a radiological and/or clinical progression of the disease. Among them, CDK4/6i were taken back for the majority of patients (n=16/22; 73 %) when the sanitary situation improved.For four patients (n=4/22; 18 %), a new specific treatment (chemotherapy or targeted therapy) was initiated for rapid or symptomatic tumor progression. Two patients died while CDK4/6i was withdrawn.All the results of the univariate analysis are summarized in Table 2. During the CDK4/6i discontinuation, the risk of disease progression was significantly increased in the presence of liver metastases. This was the only variable with a significant effect in univariate analysis.. Although not statistically significant, the risk of disease progression was higher when CDK4/6i withdrawal was longer, when patients had a more aggressive breast cancer (Luminal B) and when the tumor was considered as resistant to ET. Conclusions: The importance of maintaining the cell cycle inhibitor in addition to ET does not seem to be debatable as 36 % of patients progressed during CDK4/6i withdrawal. This is important in clinical practice when the question of CDK4/6i discontinuation arises for other reasons (analgesic radiotherapy or programmed surgery for example). Special attention should be paid to patients with liver metastases for whom stopping such a treatment seems to accelerate the natural course of the disease. Table 1.Population characteristics and evaluated variables.(CDK4/6i: 4/6 cyclin D-dependent kinase inhibitor)N. (%)Patients and variablesPatients(n=60)Disease progression (n=22)Disease stability(n=38)Age, years (upon discontinuation of CDK/6i)[35-50]12 (20)4 (18)8 (21)[50-65]19 (32)6 (27)13 (34)[65-93]29 (48)12 (55)17 (45)Cancer typeLuminal A26 (43)11 (50)15 (40)Luminal B34 (57)11 (50)23 (61)Endocrine treatmentPrimary resistance6 (10)3 (14)3 (8)Secondary resistance34 (57)15 (68)19 (50)Sensibility20 (33)4 (18)16 (42)Time between initial and metastasis diagnosisMetastases at diagnosis18 (30)5 (23)13 (34)< 5 years16 (27)8 (36)8 (21)> 5 years26 (43)9 (41)17 (45)Metastatic sitesExclusives bones metastases14 (23)4 (18)10 (26)Liver metastases (not exclusive)16 (27)11 (50)5 (13)Visceral metastases (not hepatic)30 (50)7 (32)23 (61)Duration of CDK4/6i treatment before discontinuation< 6 months25 (42)8 (36)17 (45)Between 6 months and 12 months17 (28)6 (27)11 (29)> 12 months18 (30)8 (36)10 (26)Duration of CDK4/6i treatment discontinuation< 2 months27 (45)7 (32)20 (53)≥ 2 months33 (55)15 (68)18 (47) Table 2.Univariate analysis and odds ratio for disease progression.(OR: odds ratio, CI: confidence interval, vs: versus, CDK4/6i: 4/6 cyclin D-dependent kinase inhibitor)OR95 % CIP valueAge, years (at discontinuation of CDK/6i)[35-50]1.76[50-65].92[0.20-4.31][65-93]1.41[0.35-5.78]Cancer typeLuminal A1.15Luminal B2.49[0.71-8.70]Endocrine treatmentSensibility1.07Primary or secondary resistance3.27[0.93-11.54]Disease stage at diagnosisMetastasis at initial diagnosis1.35No metastasis at initial diagnosis0.56[0.17-1.88]Metastatic sitesExclusives bones metastases1.01Liver metastases (not exclusive)5.50[1.14-26.41]Visceral metastases (not hepatic)0.76[0.18-3.20]Duration of CDK4/6i treatment before discontinuation< 6 months1.70Between 6 months and 12 months1.16[0.31-4.26]> 12 months1.70[0.49-5.95]Duration of CDK4/6i treatment discontinuation< 2 months1.12≥ 2 months2.38[0.79-7.15] Citation Format: Sophie Martin, Carole Pflumio, Philippe Trensz, Frederique Schaff-Wendling, Michal Kalish, Cathie Fischbach, Laure Pierard, Jean-Marc Limacher, Michel Velten, Thierry Petit. Consequences of stopping a 4/6 cyclin D-dependent kinase Inhibitor in metastatic breast cancer patients with clinical benefit on endocrine treatment, in the context of the COVID-19 outbreak [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-17-07.

Synchronous resection of primary colorectal cancer with liver metastases: two birds with one stone?

About one in every five patients with colorectal cancer presents with liver metastases at the time of diagnosis1. Logically, the mode of presentation drives the sequence of intervention. In patients with an urgent presentation and complications from the primary tumour, the management of intestinal obstruction, perforation or bleeding dictates treatment. Even if the acute episode is managed non-surgically, for example with use of a colonic stent for obstruction, the likelihood of advanced T category or node positivity of the primary tumour suggests that systemic chemotherapy should be the preferred treatment after resolution of the urgent issue2. Contrast-enhanced MRI of the liver and contrast-enhanced CT of the thorax after treatment of the emergency situation should be considered to document the extent of disease at baseline and before commencement of systemic chemotherapy. Patients with colorectal cancer and synchronous liver metastases may also present with either an asymptomatic or minimally/moderately symptomatic primary tumour. Should staging show metastases in more than one organ (in the context of liver metastases, this typically represents additional lung metastases), both North American and European oncology guidelines2,3 advocate systemic chemotherapy as first-line treatment. Thus, it is in the subset of patients with colorectal cancer and synchronous liver-limited metastatic disease with an asymptomatic presentation that synchronous surgery (resection of primary and liver metastases at a single operative procedure) is an option. In this setting, the practical management question of how to select patients for synchronous rather than staged surgery (resection of bowel tumour followed by hepatic resection) is an active issue (Fig. 1).

Turalio risk evaluation and mitigation strategy for treatment of tenosynovial giant cell tumor: framework and experience.

For drugs with enhanced serious safety risks, Risk Evaluation and Mitigation Strategy (REMS) may be required. Pexidartinib is approved for treatment of adult symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery. Its approval was conditional on its prescription via a mandatory REMS due to serious and potentially fatal liver injury seen in clinical trials. Turalio® REMS aims to mitigate this risk by ensuring provider education on pexidartinib use and required REMS components, prescriber adherence to baseline and periodic monitoring, and enrolling patients in a registry to further assess safe use and acute, chronic and irreversible hepatotoxicity. Through Turalio REMS, benefits of treating patients with pexidartinib may be preserved.

Early nivolumab addition to regorafenib in patients with hepatocellular carcinoma progressing under first-line therapy (GOING trial), interim analysis and safety profile.

428 Background: Regorafenib (Rego) improves survival in patients with hepatocellular carcinoma (HCC) (RESORCE trial) while nivolumab (Nivo) is also safe and active in terms of radiologic response (15-20% objective response) in second-line. The GOING trial (NCT04170556) is an investigator-initiated phase I/IIa study assessing the safety of Rego plus Nivo in HCC patients who progress and tolerate sorafenib (Cohort A) or who discontinue atezolizumab plus bevacizumab (Cohort B). Methods: Patients from cohort A receive Rego as monotherapy for the first 2 cycles (starting dose 160 mg/day, 3 weeks on/1 week off and adjusted for adverse events [AEs]) and Nivo is added at day 1 of cycle 3 (the first 10 patients at 3 mg/kg; since they did not present serious-AE (SAE), the final dose is 240 mg every two weeks). Treatment continues until unacceptable AEs, symptomatic tumor progression, patient decision or death. Safety is measured by the rate of AEs, rate of treatment related-AEs (Tr-AE), rate of AEs leading to treatment discontinuation and rate of death. Severity of AEs are evaluated according to CTCAE v.5.0. A futility analysis using the non-binding Lan & DeMets beta-spending functions with a boundary of p=0.814 is mandated when 32.8% of cohort A has data of tumor assessment at least at week 16 by RECIST 1.1. Results: Fifty-one patients have been enrolled in cohort A as of May 15, 2021. The first 30 (BCLC-C 73%) were considered in this safety analysis. All patients developed at least one AE, 29 (96.7%) had Tr-AEs of any grade and 10 (33.3%) had grade 3 (no grades 4 or 5 have been reported). Ten (33.3%) patients had a Rego-related AE, 4 (13.3%) Nivo-related, and 4 (13.3%) Tr-AE grade 3 of special interest. The table describes the profile Tr-AE occurring in > 10% of patients. Only 4 (13.3%) patients developed Tr-SAE, 3 (10 %) Rego-related and 3 (10 %) Nivo-related. Four patients discontinued the study due to physician decision, 2 for progression, and 2 for AEs (one related to study treatment). One patient had surgical resection after treatment discontinuation and a complete necrosis was observed at pathology. Conclusions: The sequential combination of Rego-Nivo has a manageable safety profile. Less than one third of the patients developed grade 3/4 Tr-AE and there was no treatment-related death. Futility analysis allowed to continuing recruitment. Clinical trial information: NCT04170556. [Table: see text]

Preoperative Prediction of Intracranial Meningioma Grade Using Conventional CT and MRI.

ObjectivePreoperative diagnosis of tumor grade can assist in treatment-related decision-making for patients with intracranial meningioma. This study aimed to distinguish between high-grade and low-grade meningiomas using conventional CT and MRI.MethodologyWe retrospectively analyzed 173 consecutive patients with intracranial meningioma (149 low-grade and 24 high-grade tumors) who were treated surgically at the National Hospital Organization Kyushu Medical Center from 2008 to 2020. Clinical and radiological features, including tumor doubling time (Td) and relative growth rate (RGR), were compared between low-grade and high-grade meningiomas.ResultsMultivariate logistic regression analysis showed that symptomatic tumor (p=0.001), non-skull base location (p=0.006), irregular tumor shape (p=0.043), tumor heterogeneity (p=0.025), and peritumoral brain edema (p=0.003) were independent predictors of high-grade meningioma. In 53 patients who underwent surgery because of tumor progression, progression to symptoms (p=0.027), intratumoral heterogeneity (p<0.001), peritumoral brain edema (p=0.001), larger tumor volume (p=0.005), shorter Td (p<0.001), and higher RGR (P<0.001) were significantly associated with high-grade meningioma. Receiver operating characteristics (ROC) curve analysis showed that the optimal Td and annual RGR cut-off values to distinguish high-grade from low-grade meningioma were 460.5 days and 73.2%, respectively (100% sensitivity and 78.6% specificity).ConclusionBased on our findings, conventional CT and MRI are useful methods to predict meningioma grades before surgery. High-grade lesions are associated with non-skull base location, irregular tumor shape, intratumoral heterogeneity, and peritumoral brain edema. High-grade meningioma should be suspected in tumors that exhibit Td <460.5 days or annual RGR >73.2% or those that develop intratumoral heterogeneity or surrounding brain edema on surveillance imaging.

CLINICOPATHOLOGICAL PROFILE OF RENAL TUMOURS IN EASTERN INDIA: A STUDY FROM TERTIARY CARE ARMED FORCES HOSPITAL

Aprimary renal tumor comprises a wide spectrum of neoplastic lesions of the kidney with patterns, which are relatively distinct among children and adults. Primary renal tumors may be benign or malignant. A wide variety of both benign and malignant renal tumors may arise from the different components of the renal parenchyma, mostly from the tubular epithelium (1,2). With the widespread use of cross sectional imaging modalities the incidence of renal tumors has been increased throughout the world during the last few decades. Until now, the gold standard treatment for most of the renal tumors is their surgical removal, either by radical nephrectomy or partial nephrectomy (3). Incidence of renal cell carcinoma (RCC) is 2-3% of all malignancy. Seventh most common tumour in western world. Country to country the incidence varies and most common in the western part of the world. Incidence of RCC is less in Asian country, particularly in India (4,5). The prole of these patients has not been studied enough in our country as yet and the data regarding RCC in India is scarce. The data available in our country either retrospective or inadequately collected. This study will help to understand characteristics of renal tumor in this geographical area and can be used as source for future reference. The study was conducted among 38 patients of renal mass from the eastern India. In the absence of robust Indian data on Renal tumours, this study provides baseline information on epidemiology, stage at presentation, and outcomes of RCC at Indian population compared with the Western population. Though symptomatic tumour still more common in India, asymptomatic tumour detection rate has been increased due to more health care facility and available imaging modalities.

Longitudinal Bottom-Up Proteomics of Serum, Serum Extracellular Vesicles, and Cerebrospinal Fluid Reveals Candidate Biomarkers for Early Detection of Glioblastoma in a Murine Model.

Glioblastoma Multiforme (GBM) is a brain tumor with a poor prognosis and low survival rates. GBM is diagnosed at an advanced stage, so little information is available on the early stage of the disease and few improvements have been made for earlier diagnosis. Longitudinal murine models are a promising platform for biomarker discovery as they allow access to the early stages of the disease. Nevertheless, their use in proteomics has been limited owing to the low sample amount that can be collected at each longitudinal time point. Here we used optimized microproteomics workflows to investigate longitudinal changes in the protein profile of serum, serum small extracellular vesicles (sEVs), and cerebrospinal fluid (CSF) in a GBM murine model. Baseline, pre-symptomatic, and symptomatic tumor stages were determined using non-invasive motor tests. Forty-four proteins displayed significant differences in signal intensities during GBM progression. Dysregulated proteins are involved in cell motility, cell growth, and angiogenesis. Most of the dysregulated proteins already exhibited a difference from baseline at the pre-symptomatic stage of the disease, suggesting that early effects of GBM might be detectable before symptom onset.

Renal cell carcinoma with widespread metastasis in 19years old young male - A rare case report.

Introduction and importanceRenal cell carcinoma is the most common malignant tumor of the kidney which occurs more frequently in men and older people than in women and young adults. Renal cell carcinoma is the second most common renal malignancy diagnosed among pediatric and adolescent patients comprising of 2% to 6% of renal cancers.Case presentationA 19 years old young adult male came with a history of epigastric and back pain, hematuria and weight loss. Per abdominal examination showed a palpable mass in the epigastric and left hypochondriac region. Radiological imaging showed diffuse infiltration of renal interstitium with multiple hypodense lesions in left kidney, renal vein infiltration, and lytic destruction of vertebral bodies and left superior pubic ramus. Fine needle aspiration cytology and trucut biopsy was taken which confirmed renal cell carcinoma, clear cell type with bone metastasis.Clinical discussionAlthough most renal cell carcinoma is sporadic and relatively uncommon in young adults, the incidence of renal cell carcinoma in this age group has steadily increased. Young adults are less likely to receive diagnosis of renal cell carcinoma incidentally. A few reported pediatric series have shown that renal cell carcinoma is highly aggressive, tends to be invasive, and metastasizes to the lungs and bones.ConclusionYoung adult with clear cell renal cell carcinoma showing wide spread metastasis is rare. Since, young age is an independent prognostic factor for cancer-specific survival, early diagnosis of the tumor will be beneficial for patients.

Significant Adverse Consequences of Initial Watchful Waiting for Follicular Lymphoma Patients: A Retrospective Analysis of Patients Diagnosed in Alberta from 1994-2011

BackgroundWatchful waiting (WW) is a widely accepted approach for asymptomatic patients with follicular lymphoma (FL) as studies have shown no survival differences between WW and immediate chemotherapy in the pre-Rituximab (R) era. The risk of WW is progressive disease resulting in significant organ dysfunction or transformation to aggressive histology lymphoma, potentially impacting quality of life and success of subsequent therapy relative to that achieved with immediate R-chemotherapy. These risks and adverse sequelae are not clearly reported in the WW literature. The objectives of our study were to evaluate the frequency of such adverse events of WW, and determine if these events impact long-term time to progression (TTP) or overall survival (OS). Additionally, we compared outcomes of R-chemotherapy for patients who were initially managed by WW with a separate dataset of patients who underwent immediate R-chemotherapy for symptomatic or high tumor burden.MethodsRecords of newly diagnosed patients aged 18-70 years with FL grade 1-3a from Calgary (1994-2011) and Edmonton (2001-2010) were retrospectively reviewed to identify those managed with an initial WW strategy (>90 days from diagnosis to first active treatment), and evaluate long-term outcomes. Baseline demographics including age, gender, stage, bulk, and FL international prognostic index (FLIPI) were recorded. Patients treated with immediate R-chemotherapy (with or without maintenance) during the same time periods from both centres were identified as a comparator group to those WW patients who were treated with R-chemotherapy at the time of progression. Study endpoints included: initial time to progression requiring therapy (TTPRT), transformation, significant organ dysfunction, TTP following first R-chemotherapy, and OS. Significant organ dysfunction categories were based on GELF high tumor burden criteria and severity of extranodal involvement decided by author consensus. Survival analysis was performed using the Kaplan-Meier method and logrank test, and p values <0.05 were considered significant.Results & DiscussionOut of a consecutively diagnosed series of 824 follicular lymphoma patients, 238 (28.5%) were initially managed with WW. Baseline demographics and outcomes are outlined in Table 1. Median follow-up (mFU) was 98.5 (9.0-256.7) months (mo) for all 238 patients, during which 169 patients (71.0%) progressed and required therapy. The median TTPRT was 46.8 mo, and by multivariate analysis was only associated with > 5 nodal sites at diagnosis (30.9 vs 55.8mo, HR 1.66 (95%CI 1.14-2.43), p=.009).Among those who progressed, 57 (23.9% of total and 33.7% progressors) developed the composite outcome of organ dysfunction or transformation (ODT) at a median of 29.9mo (3.3-114.8). There were no predictors of ODT by univariate or multivariate analyses. At the time of ODT, 56 patients received treatment with chemotherapy; R-CHOP (n=25, 43.9%), R-CVP (n=15, 26.3%), bendamustine with rituximab or obinutuzumab (n=6, 10.5%), or other regimens including non-rituximab containing chemotherapy (n=10, 17.5%). Of those who progressed requiring therapy, 10 year OS was significantly worse in those with transformation (65.4 vs 83.2%, HR 2.88, p=0.002), organ dysfunction (72.1 vs 82.6%, HR 2.04, p=0.035) and ODT (67.9 vs 85.7%, HR 3.00, p=0.001, see figure 1).Comparing the 133 WW patients who received R-chemotherapy as first treatment to a separate cohort of 236 patients who received immediate R-chemotherapy, we found no difference in TTP measured from the time of treatment initiation (p=0.51), and no difference in 10-year OS measured from time of diagnosis (p=0.612). However, 10-year OS from the time of R-chemotherapy was inferior for patients who had previously undergone a period of WW (74.4% vs. 84.0%, p=0.022). Additionally, the transformation rate during long term follow up for patients managed with initial WW who progressed requiring treatment was much higher than those who received immediate R-chemotherapy (21.1% vs. 8.1%, p=0.0003).In conclusion, our study demonstrated benefits of WW including a 29% chance of not requiring treatment at 98mo mFU. However, the risks of WW including a 24% rate of ODT and subsequent inferior OS need to be better recognized and explained to patients who consent to the WW approach. This consent process should be repeated for patients who are asymptomatic but clearly progressing during WW. [Display omitted] DisclosuresPeters:Lundbeck: Honoraria; Roche: Honoraria; Gilead: Honoraria; Abbvie: Honoraria; Janssen: Honoraria. Stewart:Gilead: Honoraria; Janssen: Honoraria; Servier: Honoraria; Amgen: Honoraria; Roche: Honoraria; Abbvie: Honoraria; Seattle Genetics: Honoraria; BMS: Honoraria; Merck: Honoraria; Lundbeck: Honoraria.

Association of Wilms tumor in multicystic dysplastic kidneys: case report and review of the literature

Multicystic dysplastic kidney is a rare urinary anomaly characterized by multiple non-communicating cysts resulting in a non-functional kidney. In addition to association with hypertension and contralateral renal anomalies, children with multicystic dysplastic kidney have an increased risk of Wilms tumor. Cohort studies and systematic reviews are hampered in estimating the true risk of this association due to the rarity and infrequent reporting of the condition. We present a case of a 2-year-old male child with an antenatal diagnosis of multicystic dysplastic kidney undergoing surveillance ultrasonography who presented with a symptomatic Wilms tumor. Level of evidence: Not applicable for this multicentre audit.

Oncological alertness in patients at outpatient therapeutic stage

Objective. Increasing the detection rate of oncological diseases in the early stages using questionnaires.Materials and methods. The study involved 25,467 patients who came to an appointment with a general practitioner / general practitioner for any request. During the study, primary care physicians, regardless of the purpose of the visit, purposefully asked questions regarding the risks of malignant neoplasms.Results. The detection rate of oncological diseases was 60.4% in the first half of 2018 against 56.3% in the same period of 2017. In accordance with specific localizations, the following results were obtained: detection of stomach cancer increased by 3%, colon cancer by 2%, malignant neoplasms of the trachea, bronchi and lungs increased by 6%, and the mammary gland, cervix and prostate increased by 1%, 8%, and 2%, respectively.Conclusions. The presence of a clear stereotype of oncological alertness in the primary care physician may contribute to a decrease in the number of advanced stages of tumors due to the initiation of specialized treatment at earlier stages. In such a situation, the main task of the therapist and general practitioner is to identify suspicious symptoms of malignant neoplasms using an algorithmized approach and refer the patient to a specialized institution.

Case series of retained rectal foreign body. A Malaysian experience.

Retained rectal foreign body, with its associated social stigma, is a medical condition that is infrequently reported in Malaysia. We report the surgical management of five cases of retained foreign objects in the rectum seen over a one-year period. There were three young and two elderly male patients. One of the elderly patients presented with altered bowel habits and an abdominal mass that mimicked a symptomatic colonic tumor. All patients had an abdominal radiograph which clinched the diagnosis of a retained foreign rectal body. Successfully retrieved objects included two bottles, one bidet device, and two sex toys. Open surgery for retrieval of the impacted rectal foreign body was required in one patient. All underwent successful retrievals without any adverse postoperative complications. In our case series, retained rectal foreign bodies were observed only in the male gender. The age presentation was bimodal, with age groups in the twenties and sixties. The treatment options used for the retrieval of these impacted foreign bodies included transanal extraction or explorative laparotomy. Proximal migration and delayed presentation are possible indications for the latter approach.

Symptomatic mastoidian brown tumor in a dialysed child

Symptomatic mastoidian brown tumor in a dialysed child

Case Series of Metastatic VIPoma With Partial Response to Somatostatin Receptor Ligand and Review of Therapeutic Options

Background: Vasoactive intestinal polypeptide secreting islet cell tumors (VIPoma) are rare neuroendocrine tumors of pancreatic origin, characterized by secretory diarrhoea and electrolyte imbalances. Metastasis, commonly hepatic, frequently occur at diagnosis in up to 80% patients. Surgery of the primary tumour remains the gold standard management and in metastatic tumors, somatostatin receptor ligands (SRL) are the drugs of choice for symptom relief and disease control. Some patients will require other approaches to control symptoms, such as liver-targeted therapy, peptide receptor radionuclide therapy (PRRT) or chemotherapy. We describe a case series of metastatic VIPoma which partially-responded to SRL and review of other treatment modalities to achieve disease and symptom control. Case: We report 3 cases, ages 37 to 58 years, with metastatic VIPoma whom presented with secretory diarrhoea, hypokalaemia, achlorhydria and elevated serum VIP levels. CT and 68Gallium PET-CT imaging identified metastases in liver, bone, lungs, spleen and lymph nodes. One case underwent distal pancreatectomy and splenectomy at diagnosis and two cases were advanced and non-resectable. All received long-acting SRL initially and achieved partial control of the gastrointestinal symptoms. Two cases underwent Peptide Receptor Radionuclide Therapy (PRRT) and one case received cytotoxic chemotherapy. Two patients have progressive disease and one succumbed to advanced disease. For inoperable disease, PRRT is useful adjuvant therapy for symptom relief and may improve progression free survival (PFS). Cytotoxic chemotherapy is an option for patients with progressive or symptomatic unresectable tumor. Chemoembolization or liver-targeted therapy are used in liver metastasis for loco-regional control. Alfa-interferon and targeted therapies such as everolimus and sunitinib are other treatment options that can be considered. Conclusion: Metastatic VIPoma remains a challenging disease to manage, requiring multimodal treatment approaches. With timely diagnosis and advancing therapeutic options, more patients can achieve improved symptom and disease control as well as increased survival.

A Unique Presentation of Metastatic Follicular Thyroid Cancer Associated with Hyperthyroidism and an Active Graves’ Orbitopathy

Background: Graves orbitopathy (GO) developing in a thyroidectomized patient with hormonally active metastatic follicular thyroid cancer (FTC) is an extremely rare event. We report a unique patient with GO and hyperthyroidism developing 13 years after FTC diagnosis. Case: A 79-year-old Caucasian female diagnosed with FTC T3N0M1 with lung metastases in 2005, was treated with total thyroidectomy and cumulative radioiodine (RAI) activity of 700 mCi between 2005 and 2010, with post-treatment scans revealing RAI-avid disease. Despite RAI treatment-associated stable disease in the lungs, the patient developed bone metastases and required external beam radiation (EBRT; 30 Gy in 10 fractions) to the left acetabular lesion in 2011. In 2015, she presented with clinically symptomatic tumor growth in the lungs and bones and biochemical disease progression with thyroglobulin levels rising from 255 ng/ml in 2014 to 273141 ng/mL in 2019. The patient completed repeat EBRT to the left iliac bone in December 2019 (30 Gy in 10 fractions). She was on weight-based suppressive levothyroxine treatment between 2005 and 2019 until she developed atrial fibrillation with a rapid ventricular response and was diagnosed with thyrotoxicosis with TSH < 0.01 mIU/mL (normal0.36 - 5.60) and free T4 5.93 ng/dL (normal 0.9 - 1.7). An iatrogenic cause of thyrotoxicosis was ruled out on the basis of persistent clinical and biochemical hyperthyroidism after reduction, and subsequently, cessation of levothyroxine treatment. Further workup was significant for elevated thyroid stimulated immunoglobulin (TSI) of 23.9 IU/l (normal: < 1.3) and thyrotropin receptor antibodies (TRAb) of 10.39 IU/L (< or =1.75), consistent with Graves’ disease. The patient achieved and maintained euthyroidism on methimazole treatment. In April 2019, she was diagnosed with active GO and was treated with intravenous methylprednisolone, which was discontinued four weeks later due to steroids-induced severe myopathy. Given a high clinical activity score of 6 and magnetic resonance imaging of the orbits revealing a significant bilateral symmetric extraocular muscle enlargement and increased retro-orbital fat with no evidence of optic nerve compromise, she underwent radiation therapy to the orbits (20 Gy in 10 fractions), which was completed in December 2019. Subsequently, in 2020, the patient underwent 8 cycles of treatment with a monoclonal antibody against insulin-like growth factor I receptor - teprotumumab. Subjectively, she reported improved eye swelling and no vision changes, but developed drug-induced partial hearing loss, which is thought to be reversible. Conclusion: Metastatic, progressive FTC can be associated with an autoimmune response, leading to stimulation of well-differentiated cancer tissue to overproduce thyroid hormones resulting in overt hyperthyroidism, as well as retroorbital fibroblasts activation leading to GO.

CYP3A Mediated Metabolism of Tyrosine Kinase Inhibitor Pexidartinib and Alleviated its Cytotoxicity to HepG2 Cells

Pexidartinib (PLX, TURALIOTM) is a novel small molecule tyrosine-kinase inhibitor with highly selective activity against colony-stimulating factor-1 receptor. PLX was developed for the treatment of symptomatic tenosynovial giant cell tumor in adult patients and approved by the US FDA in 2019. Despite its effectivity, frequently reported clinical cases with severe hepatotoxicity led to a black-box warning issued to PLX by the FDA. However, the mechanisms of PLX-induced hepatotoxicity remain largely unknown and the roles of PLX metabolism in its toxicity have not been investigated. Using liquid chromatography/mass spectrometry-based metabolomic approaches, this study revealed 36 PLX metabolites in human liver microsome (HLM) and mouse liver microsome (MLM), including characterized 11 glutathione (GSH) -PLX adducts and 3 methoxyamine-trapped aldehydes (hydrazones). Using recombinant cytochrome P450 enzymes, CYP3A4 and CYP3A5 were identified as the primary enzymes contributing to the formation of major metabolites, GSH-PLX adducts, and methoxyamine-trapped hydrazones. Their formation was significantly suppressed by the CYP3A inhibitor ketoconazole and in the liver S9 fraction of Cyp3a-null mice, further confirming the role of CYP3A in PLX Phase I metabolism. More interestingly, we found that PLX is less toxic to CYP3A4- or CYP3A5-overexpressed HepG2 cells compared to their counterpart HepG2 cells transduced with empty vector, indicating that CYP3A-mediated metabolism attenuates PLX cytotoxicity to HepG2. In summary, 36 PLX metabolites including 11 GSH adducts and 3 hydrazones were identified in HLM and MLM. CYP3A4 and CYP3A5 are responsible for the Phase I biotransformation of PLX and alleviate its cytotoxicity in HepG2. Further studies are warranted to elucidate the role of metabolism in PLX hepatotoxicity and the mechanism associated with PLX-induced liver injury.

MR-Guided Radiotherapy for Brain and Spine Tumors.

MRI is the standard modality to assess anatomy and response to treatment in brain and spine tumors given its superb anatomic soft tissue contrast (e.g., T1 and T2) and numerous additional intrinsic contrast mechanisms that can be used to investigate physiology (e.g., diffusion, perfusion, spectroscopy). As such, hybrid MRI and radiotherapy (RT) devices hold unique promise for Magnetic Resonance guided Radiation Therapy (MRgRT). In the brain, MRgRT provides daily visualizations of evolving tumors that are not seen with cone beam CT guidance and cannot be fully characterized with occasional standalone MRI scans. Significant evolving anatomic changes during radiotherapy can be observed in patients with glioblastoma during the 6-week fractionated MRIgRT course. In this review, a case of rapidly changing symptomatic tumor is demonstrated for possible therapy adaptation. For stereotactic body RT of the spine, MRgRT acquires clear isotropic images of tumor in relation to spinal cord, cerebral spinal fluid, and nearby moving organs at risk such as bowel. This visualization allows for setup reassurance and the possibility of adaptive radiotherapy based on anatomy in difficult cases. A review of the literature for MR relaxometry, diffusion, perfusion, and spectroscopy during RT is also presented. These techniques are known to correlate with physiologic changes in the tumor such as cellularity, necrosis, and metabolism, and serve as early biomarkers of chemotherapy and RT response correlating with patient survival. While physiologic tumor investigations during RT have been limited by the feasibility and cost of obtaining frequent standalone MRIs, MRIgRT systems have enabled daily and widespread physiologic measurements. We demonstrate an example case of a poorly responding tumor on the 0.35 T MRIgRT system with relaxometry and diffusion measured several times per week. Future studies must elucidate which changes in MR-based physiologic metrics and at which timepoints best predict patient outcomes. This will lead to early treatment intensification for tumors identified to have the worst physiologic responses during RT in efforts to improve glioblastoma survival.

Recurrent Pituitary Tumor and Use of Minidoppler to Avoid Carotid Artery Injury

Study objective: To learn how to avoid injury to the carotid artery during recurrent pituitary surgery. Design: Through transsphenoidal endonasal approach the steps of surgery with avoidance of complications were described in the video particularly the use of Minidoppler was to localise the carotids. Setting: Comfort Nursing Home, a private hospital in Dhaka, Bangladesh. Subject/Audience: Neurosurgeons/Residents. Intervention: Demonstration of transsphenoidal endonasal approach for recurrent pituitary tumor and use of Minidoppler to avoid carotid artery injury. Results: Avoidance of complications like intraoperative accidental injury to carotids where symptomatic tumor is small and inter carotid distance is less. Taking this into account, we created this video to demonstrate the important steps specifically to use Minidoppler to avoid a devastation like carotid artery injury. Conclusion: The steps of recurrent pituitary surgery through endonasal approach is well established. To evaluate the details of anatomical structures specifically the inter carotid distance prior to surgery will prevent the unwanted complications in recurrent pituitary surgery and with high resolution monitoring and use of Minidoppler, carotid arteries can be localised.

Comparative Analysis of Presentation and Outcome After Liver Resection of Patients With Hepatocellular Carcinoma With and Without HIV.

Evidence shows that HIV infection may affect the survival outcome of patients with hepatocellular carcinoma (HCC). In this article, we aimed to determine whether HIV affected the overall survival of patients with HCC in China and ascertain the risk factors. Retrospective cohort study. Participants were enrolled from a single medical center in Guangzhou, China. Survival was assessed using Kaplan-Meier plots and compared using the log-rank test. A multivariable Cox regression analysis was used to assess the effect of HIV seropositivity on patient overall survival while accounting for common prognostic factors. The Kaplan-Meier plots showed that the median survival time of patients who were HIV-positive was 18 months shorter than that of their HIV-negative counterparts (P = 0.00, log rank). The 1- and 3-year rates of survival for HIV-positive patients were 65.4% and 29.9%, which were 93.3% and 79.1% for HIV-negative patients. The death rate due to tumor recurrence and liver failure in the HIV-positive patients was apparently higher than those of the HIV-negative patients (tumor recurrence, 42.3% vs. 17.3%, P = 0.016; liver failure, 19.2% vs. 2.7%, P = 0.012, respectively). Independent factors predicting survival were initial presentation, HIV serostatus, United Network of Organ Sharing-modified tumor-node-metastasis stage, Barcelona Clinic Liver Cancer stage, aspartate aminotransferase, histological pattern, and microvascular invasion. HIV-positive subjects with HCC have a poorer survival outcome than their HIV-negative counterparts, with tumor recurrence and liver failure as the main causes of death. Despite adequate curative therapy, HIV serostatus is associated with decreased survival of patients with HCC, independent of symptomatic presentation, tumor staging, and liver function.