Local Tissue Invasion Research Articles

Adaptive segmentation-to-survival learning for survival prediction from multi-modality medical images

Early survival prediction is vital for the clinical management of cancer patients, as tumors can be better controlled with personalized treatment planning. Traditional survival prediction methods are based on radiomics feature engineering and/or clinical indicators (e.g., cancer staging). Recently, survival prediction models with advances in deep learning techniques have achieved state-of-the-art performance in end-to-end survival prediction by exploiting deep features derived from medical images. However, existing models are heavily reliant on the prognostic information within primary tumors and cannot effectively leverage out-of-tumor prognostic information characterizing local tumor metastasis and adjacent tissue invasion. Also, existing models are sub-optimal in leveraging multi-modality medical images as they rely on empirically designed fusion strategies to integrate multi-modality information, where the fusion strategies are pre-defined based on domain-specific human prior knowledge and inherently limited in adaptability. Here, we present an Adaptive Multi-modality Segmentation-to-Survival model (AdaMSS) for survival prediction from multi-modality medical images. The AdaMSS can self-adapt its fusion strategy based on training data and also can adapt its focus regions to capture the prognostic information outside the primary tumors. Extensive experiments with two large cancer datasets (1380 patients from nine medical centers) show that our AdaMSS surmounts the state-of-the-art survival prediction performance (C-index: 0.804 and 0.757), demonstrating the potential to facilitate personalized treatment planning.

Orbital solitary fibrous tumor

Introduction: Solitary fibrous tumor (SFT) is a rare borderline mesenchymal tumor typically arising in the pleura and involving the orbit as its most common extra-pleural locationCase description: We herein describe two cases of orbital SFT arising in both a 69-year-old woman presenting with progressive proptosis of the left eye and a 49-year-old woman presenting with binocular diplopia. The diagnoses relied on histopathological analysis of biopsy samples. Because of the poor local prognosis, we decided to perform an orbital exenteration in the first case. In the second case, a complete resection surgery was performed.Conclusion: SFT presents classics histological features and immunohistochemical markers that are essential to the diagnosis.SFT is classified as a benign tumor, but in some cases, it can show aggressive behavior with the potential for local tissue invasion and, more scarcely, distant metastasis. This is why complete resection remains the treatment of choice for SFT.

P-325 Evidence for dysregulation of oncogene pathways at the gene expression level in the epithelium of deep infiltrating endometriosis compared to adenomyosis

Abstract Study question How does the gene expression profile of epithelium cells differ between deep infiltrating endometriosis (DIE) and adenomyosis (FA)? Summary answer The gene expression of epithelial cells from DIE reveals a significant upregulation of the PI3K-pathway and downregulation of the RAS-pathway compared to epithelium from FA. What is known already Both DIE and FA, are histologically considered benign but have features of malignant diseases, such as a tendency for local tissue invasion. Recent next generation sequencing studies have detected driver mutations in cancer-associated genes such as PIK3CA, ARID1A, PPP2R1A and KRAS in the epithelium of DIE, as well as in KRAS in epithelium of FA. Furthermore, identical mutations in the KRAS gene were detected in coexisting adenomyotic and endometriotic lesions, supporting the theory of a common molecular mechanism. The gene expression differences between these two entities were therefore investigated in the present study. Study design, size, duration This is an experimental analysis of 7 adenomyosis and 19 DIE samples (histologically confirmed), that were formalin-fixed and paraffin-embedded (FFPE) collected between 2003 and 2018. These were provided by the tissue bank of the National Centre for Tumour Diseases (Heidelberg, Germany), in accordance with the Ethics Committee of the University of Heidelberg (approval number S-362/2017). In addition, the medical and epidemiological data of the corresponding patients were retrospectively analyzed based on the clinical data collected. Participants/materials, setting, methods For this study, the epithelia of FFPE samples were microdissected in a laser-guided fashion. After RNA extraction, the expression of 770 genes was analyzed using the nCounter Technology with the Human PanCancer Pathways Panel (Nanostring). All genes with an adjusted false discovery rate of p < 0.05 and a fold change of < 0.66 or > 1.5 were considered differentially expressed and subjected to functional annotation and clustering using DAVID bioinformatics resources. Main results and the role of chance Our analysis revealed a total of 162 differentially expressed genes, that were either significantly increased (n = 116) or decreased (n = 46) in epithelium of DIE compared to that of FA (with log2 fold changes of < 0.66 or > 1.5 and an adjusted p-value of < 0.05). Gene ontology and KEGG pathway analysis for genes with increased expression in DIE compared with FA revealed significant upregulation of genes belonging to the PI3K-pathway and the focal adhesion pathway, as well as pathways related to viral infection, endocrine resistance, and malignancy. The upregulated pathways in adenomyosis mainly included the RAS-pathway. Limitations, reasons for caution The average age of DIE patients was lower, but many of them were hormonally inactive due to GnRH analogues, which mitigates any age-related differences. Furthermore, only relative expression was studied between the groups without comparison to normal endometrium. Overall, the sample size is relatively small and further studies are needed. Wider implications of the findings The expression of different signaling pathways in the two entities could, for example, explain the different sensitivity of the two diseases to certain therapeutic approaches. While DIE responds well to therapy with the progestogen dienogest, progesterone resistance is often described in adenomyosis patients. Trial registration number not applicable

Rhino-Orbital Cerebral Mucormycosis in a Diabetic Patient: An Emergency Medicine Case Report

BackgroundRhino-orbital cerebral mucormycosis (ROCM) is a rare infection caused by an invasive fungus and found predominantly in immunocompromised patients. The presentation of ROCM ranges from a mild headache, fever, and sinusitis to vision loss, altered mental status, and facial disfigurement secondary to local tissue invasion. ROCM can cause significant morbidity and mortality and requires prompt diagnosis with timely evaluation by surgical and infectious disease specialists. Cases of ROCM have been reported extensively in internal medicine, infectious disease, and otolaryngology literature. However, there are very few reports in emergency medicine literature in the United States. Case ReportA 72-year-old woman presented to the Emergency Department (ED) with altered mental status, 4 days of left-sided facial numbness and weakness, and sudden facial pain, swelling, and erythema. Laboratory analysis was consistent with diabetic ketoacidosis. Noncontrast computed tomography of the head and magnetic resonance imaging of the brain demonstrated findings indicative of invasive fungal infection of the left sinus and orbit with extension to the cavernous sinus and surrounding cranial nerves. She was initiated on broad-spectrum antifungals, but based on the extent of the infection, was not a surgical candidate. She subsequently transitioned to a comfort-based plan of care and died 6 days after initial ED presentation. Why Should an Emergency Physician Be Aware of This?Early recognition and initiation of treatment can potentially mitigate the devastating outcomes of ROCM, therefore it is critical to be aware of this condition and have a high level of suspicion in susceptible patients.

PSAT211 Low Grade Parathyroid Carcinoma: A Challenging Diagnosis in the Evaluation of Primary Hyperparathyroidism

Abstract Background Parathyroid carcinoma often presents with severe symptomatic hypercalcemia, bone and kidney involvement, and PTH > 4x the upper limit of normal. Diagnosis is challenging and requires classic pathologic findings. Case Presentation A 34-year-old woman presented with hypercalcemia. She was found to have primary hyperparathyroidism with elevated total calcium (11.8 mg/dL), elevated PTH (352.8 pg/mL), and elevated 24-hour urine calcium (758 mg/24hr). A 99mTc sestamibi scan showed focal uptake in the right inferior thyroid pole. Intraoperatively, there was a lobulated, fibrotic right parathyroid mass sized 3.5×2.5×2.0 cm. Pathology showed low-grade parathyroid carcinoma with lymphovascular invasion, extension into soft tissue, and focal positivity in resection margin. Post-operative PTH was 19.5 pg/mL. One month later, PTH was elevated to 82.0 pg/mL with calcium of 9.1 mg/dL. PET scan did not show metastases. The patient then underwent a right thyroid lobectomy with central compartment lymph node dissection. Pathology showed residual parathyroid carcinoma within the perithyroidal scar tissue but was negative for lymph node involvement. Postoperatively, her PTH was 52.5 pg/mL. Genetic studies showed no mutations in CDC73, MEN1, RET, RB1, and TP53 genes. She underwent external beam radiation treatment. Following radiation, her total calcium and PTH level remained in the normal range with no recurrence on thyroid ultrasound. Clinical Lessons On ultrasound, parathyroid carcinomas are large, have increased heterogeneity and lobulations, as well as suspicious lymph nodes. Intraoperative suspicion is based on large size, capsular or local tissue invasion, and lymph node metastases. Histologic assessment can be challenging as findings of parenchymal mitoses, trabeculated parenchyma, and thick fibrous bands are also seen with parathyroid adenomas. Local tissue invasion (angiolymphatic, perineural or adjacent structures) or metastases such as lymph nodes seen on pathology are diagnostic of parathyroid carcinoma. PET can be used post-operatively to identify recurrence or metastases. Genetic studies especially for mutations in CDC73 can be helpful in diagnosis as it is the most common cause of syndromic and sporadic parathyroid carcinoma.Resection of the tumor and adjacent tissues is the mainstay of treatment. A regional lymph node dissection should be done if there are suspicious lymph nodes. Neither thyroidectomy, chemotherapy nor radiation has been shown to improve overall survival. Radiation has shown to have some benefit for local recurrence and disease-free survival. Lifelong monitoring of calcium and PTH levels is required, and if elevated, should prompt imaging with thyroid ultrasound and PET scan. Prognosis is generally poor but does improve if there is complete surgical resection on initial diagnosis. Almost all patients experience recurrence within 2-23 years after resection Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

TRAF3IP2–IL-17 Axis Strengthens the Gingival Defense against Pathogens

Recent genome-wide association studies have suggested novel risk loci associated with periodontitis, which is initiated by dysbiosis in subgingival plaque and leads to destruction of teeth-supporting structures. One such genetic locus was the tumor necrosis factor receptor–associated factor 3 interacting protein 2 (TRAF3IP2), a gene encoding the gate-keeping interleukin (IL)–17 receptor adaptor. In this study, we first determined that carriers of the lead exonic variant rs13190932 within the TRAF3IP2 locus combined with a high plaque microbial burden was associated with more severe periodontitis than noncarriers. We then demonstrated that TRAF3IP2 is essential in the IL-17–mediated CCL2 and IL-8 chemokine production in primary gingival epithelial cells. Further analysis suggested that rs13190932 may serve a surrogate variant for a genuine loss-of-function variant rs33980500 within the same gene. Traf3ip2 null mice (Traf3ip2–/–) were more susceptible than wild-type (WT) mice to the Porphyromonas gingivalis–induced periodontal alveolar bone loss. Such bone loss was associated with a delayed P. gingivalis clearance and an attenuated neutrophil recruitment in the gingiva of Traf3ip2–/– mice. Transcriptomic data showed decreased expression of antimicrobial genes, including Lcn2, S100a8, and Defb1, in the Traf3ip2–/– mouse gingiva in comparison to WT mice prior to or upon P. gingivalis oral challenge. Further 16S ribosomal RNA sequencing analysis identified a distinct microbial community in the Traf3ip2–/– mouse oral plaque, which was featured by a reduced microbial diversity and an overabundance of Streptococcus genus bacteria. More P. gingivalis was observed in the Traf3ip2–/– mouse gingiva than WT control animals in a ligature-promoted P. gingivalis invasion model. In agreement, neutrophil depletion resulted in more local gingival tissue invasion by P. gingivalis. Thus, we identified a homeostatic IL-17-TRAF3IP2-neutrophil axis underpinning host defense against a keystone periodontal pathogen.

DeepMTS: Deep Multi-Task Learning for Survival Prediction in Patients With Advanced Nasopharyngeal Carcinoma Using Pretreatment PET/CT.

Nasopharyngeal Carcinoma (NPC) is a malignant epithelial cancer arising from the nasopharynx. Survival prediction is a major concern for NPC patients, as it provides early prognostic information to plan treatments. Recently, deep survival models based on deep learning have demonstrated the potential to outperform traditional radiomics-based survival prediction models. Deep survival models usually use image patches covering the whole target regions (e.g., nasopharynx for NPC) or containing only segmented tumor regions as the input. However, the models using the whole target regions will also include non-relevant background information, while the models using segmented tumor regions will disregard potentially prognostic information existing out of primary tumors (e.g., local lymph node metastasis and adjacent tissue invasion). In this study, we propose a 3D end-to-end Deep Multi-Task Survival model (DeepMTS) for joint survival prediction and tumor segmentation in advanced NPC from pretreatment PET/CT. Our novelty is the introduction of a hard-sharing segmentation backbone to guide the extraction of local features related to the primary tumors, which reduces the interference from non-relevant background information. In addition, we also introduce a cascaded survival network to capture the prognostic information existing out of primary tumors and further leverage the global tumor information (e.g., tumor size, shape, and locations) derived from the segmentation backbone. Our experiments with two clinical datasets demonstrate that our DeepMTS can consistently outperform traditional radiomics-based survival prediction models and existing deep survival models.

Surgical treatment and long-term outcomes of low-grade myofibroblastic sarcoma: a single-center case series of 15 patients

BackgroundLow-grade myofibroblastic sarcoma (LGMS) is a poorly studied, rare, soft tissue sarcoma. LGMS is characterized by a low malignancy potential, tendency for local recurrence, and low likelihood of distant metastases. However, no studies have reported on the surgical treatment method and its long-term outcomes.MethodsWe included all patients treated for LGMS at our institution between March 2010 and March 2021. Medical charts were retrospectively reviewed to collect demographic information, as well as information about the clinical course, tumor characteristics, and outcomes. Statistical analysis was performed to identify the factors associated with the recurrence rate.ResultsFifteen patients who underwent surgical treatment were enrolled in this study. There were seven cases in the upper extremities, four in the trunk area, three in the lower extremities, and one in the head and neck area. There were no metastatic cases and two cases of local recurrence.ConclusionsThe incidence of LGMS in the extremities or trunk may be higher than expected based on the current literature. Univariate analysis showed that local tissue invasion and surgical method could be associated with local recurrence. Although further large studies are needed to establish risk factors of local recurrence or extent of resection margins, based on our study, wide local excision under the proper diagnosis is the most important treatment.

The chemotherapy effect on embryonal rhabdomyosarcoma in a 2-year-old girl in a development country: A rare case

Rhabdomyosarcoma (RMS) is the third most common solid organ malignancy in children after Wilms tumor and neuroblastoma. It is a highly malignant tumor with local tissue invasion and lymphatic and hematogenous metastases. The main treatment for RMS is complete resection with a combination of chemotherapy and radiotherapy. Here, we present the case of a 2-year-old girl who came to the hospital with a complaint of noisy breathing (Stridor) for the past 2 weeks. Intraoral examination showed an oval mass at the base of the tongue that almost closed the airway, felt soft, and had a bump. A computed tomography scan of the neck was performed, and a solid lesion with clear irregular borders was found in the posterior lingua. Incisional biopsy was performed with histopathological results of embryonal RMS. Two weeks after the biopsy, chemotherapy was performed, and the evaluation after two chemotherapy sessions, the mass size was found to have decreased.

Innovative Biomaterials for the Treatment of Bone Cancer.

Bone cancer is a demanding challenge for contemporary medicine due to its high frequency of presentation and significant heterogeneity of malignant lesions developing within the bone. To date, available treatments are rarely curative and are primarily aimed at prolonging patients’ survival and ameliorating their quality of life. Furthermore, both pharmacological and surgical therapies are aggravated by a consistent burden of adverse events and subsequent disability due to the loss of healthy bone structural and functional properties. Therefore, great research efforts are being made to develop innovative biomaterials able to selectively inhibit bone cancer progression while reducing the loss of bone structural properties secondary to local tissue invasion. In this review, we describe the state of the art of innovative biomaterials for the treatment of bone cancer. Along with physiological bone remodeling, the development of bone metastasis and osteosarcoma will be depicted. Subsequently, recent advances on nanocarrier-based drug delivery systems, as well as the application of novel, multifunctional biomaterials for the treatment of bone cancer will be discussed. Eventually, actual limitations and promising future perspectives regarding the employment of such approaches in the clinical scenario will be debated.

Hypoxia in Breast Cancer—Scientific Translation to Therapeutic and Diagnostic Clinical Applications

Breast cancer has been the leading cause of female cancer deaths for decades. Intratumoral hypoxia, mainly caused by structural and functional abnormalities in microvasculature, is often associated with a more aggressive phenotype, increased risk of metastasis and resistance to anti-malignancy treatments. The response of cancer cells to hypoxia is ascribed to hypoxia-inducible factors (HIFs) that activate the transcription of a large battery of genes encoding proteins promoting primary tumor vascularization and growth, stromal cell recruitment, extracellular matrix remodeling, cell motility, local tissue invasion, metastasis, and maintenance of the cancer stem cell properties. In this review, we summarized the role of hypoxia specifically in breast cancer, discuss the prognostic and predictive value of hypoxia factors, potential links of hypoxia and endocrine resistance, cancer hypoxia measurements, further involved mechanisms, clinical application of hypoxia-related treatments and open questions.

A mathematical multi-organ model for bidirectional epithelial–mesenchymal transitions in the metastatic spread of cancer

AbstractCancer invasion and metastatic spread to secondary sites in the body are facilitated by a complex interplay between cancer cells of different phenotypes and their microenvironment. A trade-off between the cancer cells’ ability to invade the tissue and to metastasize, and their ability to proliferate has been observed. This gives rise to the classification of cancer cells into those of mesenchymal and epithelial phenotype, respectively. Additionally, mixed phenotypic states between these two extremes exist. Cancer cells can transit between these states via epithelial–mesenchymal transition (EMT) and the reverse process, mesenchymal–epithelial transition (MET). These processes are crucial for both the local tissue invasion and the metastatic spread of cancer cells. To shed light on the role of these phenotypic states and the transitions between them in the invasive and metastatic process, we extend our recently published multi-grid, hybrid, individual-based mathematical metastasis framework (Franssen et al. 2019, A mathematical framework for modelling the metastatic spread of cancer. Bull. Math. Biol., 81, 1965). In addition to cancer cells of epithelial and of mesenchymal phenotype, we now also include those of an intermediate partial-EMT phenotype. Furthermore, we allow for the switching between these phenotypic states via EMT and MET at the biologically appropriate steps of the invasion-metastasis cascade. We also account for the likelihood of spread of cancer cells to the various secondary sites and differentiate between the tissues of the organs involved in our simulations. Finally, we consider the maladaptation of metastasized cancer cells to the new tumour microenvironment at secondary sites as well as the immune response at these sites by accounting for cancer cell dormancy and death. This way, we create a first mathematical multi-organ model that explicitly accounts for EMT-processes occurring at the level of individual cancer cells in the context of the invasion-metastasis cascade.

Osteopontin Regulates Endometrial Stromal Cell Migration in Endometriosis through the PI3K Pathway

Endometriosis is generally characterized as a tumor-like disease because of its potential for distant metastasis and local tissue invasion, while whether osteopontin (OPN) plays a role in the pathogenesis of endometriosis has not been thoroughly investigated. We investigated the expression of OPN, urokinase plasminogen activator (uPA), phosphatidylinositol 3 kinase (PI3K), and phospho-PI3 kinase (p-PI3K) in endometrial stromal cells (ESCs). The serum concentration of OPN was determined by enzyme-linked immunosorbent assays (ELISA). OPN was downregulated to explore the corresponding change of uPA, p-PI3K, F-actin, and α-tubulin. The expression of OPN, uPA, PI3K, and p-PI3K was evaluated by western blot and quantitative real-time PCR (RT-qPCR) and the expression of F-actin and α-tubulin was confirmed by immunofluorescence assay. The proliferation and migration abilities of ESCs were investigated by CCK8, transwell, and wound scratch assays. Endometrial OPN, p-PI3K, and uPA expressions and serum OPN levels were increased in patients with endometriosis compared with the control. The expressions of p-PI3K, uPA, and α-tubulin were decreased by siRNA-OPN interference in ectopic ESCs. Activation and inhibition of the PI3K pathway apparently upregulate and downregulate uPA expression. Knockdown of OPN and inhibition of the PI3K pathway remarkably inhibited cell migration in ectopic ESCs. Meanwhile, activation of the PI3K pathway promoted the migration ability of ectopic ESCs. OPN may regulate the expression of uPA through the PI3K signal pathway to affect the migration ability of ESCs, indicating that OPN, uPA, and the PI3K pathway may be potential targets for interrupting development of endometriosis.

Merkel Cell Carcinoma: A Case-Report of Rare Presentation of Merkel Cell Carcinoma, Non-Indolent Proliferative Type, Polyomavirus-Negative: Hypothesis of MolecularPathogenesis

Introduction: Merkel cell carcinoma (MCC) is a rare cutaneous indolent neuroendocrine cancer, arising from the Merkel cells of the stratum basalis, of the epidermis. This type of tumor commonly arises in sun-exposed areas, such as head, neck, and lower extremities. Here, we describe a rare presentation of non-indolent proliferative type Merkel cell carcinoma. Case Report: This is a case-report of a 70-year-old Caucasian man with no pertinent past medical history, presenting as a large painless violaceous necrotic irregular bordered rapidly growing lesion, reaching to 8x10x15 cm3, within one-year period, on the lower back region with surface ulceration. Pelvic MRI showed a multilobulated enhancing soft tissue mass measuring 8.7x10.4x15.1 cm3 at the left gluteal region with exophytic extension to the left paraspinal muscles. The patient was admitted, tangential surgical excision and debridement of left flank wound was performed with partial primary closure. Pathology showed features of Merkel cell, show diffuse dot-like positivity with CK20 and are negative for CK7, there is diffuse positivity with NSE, synaptophysin and CD56 with strong diffuse Ki-67 positivity noted in >65% of tumor cells. CD99 shows diffuse small faint dot-like paranuclear positivity. Discussion: Merkel cell carcinoma (MCC) is a rare, aggressive tumor that generally arises in sun-exposed regions. After an initial course of slow growth, starting as a painless violaceous non-pruritic domed-shaped lesion, the tumor becomes more aggressive, rapidly growing, with metastasis with local lymph nodes and regional tissue invasion. Sixty percent of tumors can rapidly grow within a three-month period after initial diagnosis. MCC is also clonally associated with is polyomavirus. MCC Contributing molecular pathogenesis is imperative to determining the causation of rare non-indolent MCC tumors, and its association with prognosis and treatment. In polyomavirus negative patients, consideration for molecular pathogenesis as etiology is imperative.

1634 Extracolonic Neoplasm From Colonic Polyps: A Case of Metastatic Prostate Cancer Diagnosed From a Colonic Polyp

INTRODUCTION: Prostate Cancer is the 2nd most common cancer among men in the US. Prostate Cancer frequently metastasizes to the bones, lymph nodes, lungs, liver, and brain. Very rarely, patients can develop metastases to the GI tract. We are presenting a patient that was diagnosed with metastatic prostate cancer after a colon biopsy. CASE DESCRIPTION/METHODS: A 61-year-old gentleman with no significant past medical history, presented with constipation, weak urinary stream, in addition to remote fall followed by lower back pain, trouble ambulating, and an unintentional 40 lb weight loss. He did not have any history of melena, hematochezia, abdominal pain or family history of cancers Examination was only evident of tenderness overlying lumbar vertebrae. He underwent CT Abdomen/Pelvis which showed sclerotic vertebral bone lesions in addition to abnormal thickening of the mid to lower rectal wall with adjacent perirectal soft tissue masses suspicious for rectal cancer with adjacent conglomerate lymphadenopathy/tumor. Colonoscopy revealed diminutive sigmoid sessile polyps which was removed by cold snare and cold biopsy in addition to an area of ulceration in the proximal rectum. Surprisingly the pathology of the polyps and rectal ulceration was consistent with metastatic prostate adenocarcinoma. He is planned to be started on chemotherapy with Docetaxel. DISCUSSION: Prostate cancer may invade the rectum however it remains rare to have metastatic colonic polyps from a prostate cancer. It has been reported to discover metastatic colonic polyps from breast, lung, skin (melanoma) cancer, however the finding of metastatic colonic polyps from a prostate cancer is rare and portends a sinister prognosis. In the light of this infrequent finding it becomes imperative to consider an extracolonic cause as the source of a colonic polyp especially in patients with known or in suspicion for a primary cancer. The mechanism of metastasis to the colonic is thought to be by hematogenous or lymphatic spread, however, rectal involvement often occurs by local tissue invasion. The clinical scenario in our patient is peculiar since there were no prior diagnoses of primary cancer. An extracolonic metastatic polyp may sometimes be the earliest sign of recurrent prostate cancer.

THE CASE OF THE FUNGUS IN THE HONEYCOMB

SESSION TITLE: Monday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Aspergillomas are fungal balls that typically develop in pre-existing pulmonary cavities such as those caused by tuberculosis, sarcoidosis, histoplasmosis, cystic fibrosis and lung abscesses but are rarely associated with UIP. Aspergillomas are typically distributed as either multiple bilateral pulmonary aspergillomas or as an isolated aspergilloma. The most commonly reported cases of aspergillomas have been found in post-tuberculosis cavities, accounting for 11 to 17% of cases, with an increased incidence in areas of high tuberculosis prevalence. For this reason, aspergillomas are typically found in the upper lobes with lower/middle lobe findings often associated with other cavitary pulmonary diseases. CASE PRESENTATION: We present an unusual case of multiple, unilateral aspergillomas in a non-immunocompromised patient with usual interstitial pneumonia (UIP). Patient is a 73-year-old female with seropositive rheumatoid arthritis (not on immunosuppressive therapy) who was evaluated for weight loss and minor hemoptysis. Chest CT showed classic bibasilar honeycomb changes typical of UIP. There were nodular opacities within the honeycomb changes suggestive of mycetomas seen exclusively in the right lung base. These were subsequently identified as aspergillomas by correlating the chest CT with bronchoscopic cultures that grew A. fumigatus. The patient’s symptoms resolved spontaneously after 6 months without treatment for either aspergillomas or UIP. At follow up after 2 years, the patient remained symptom free without further episodes of hemoptysis and her weight was stable. DISCUSSION: This case is a unique presentation for several reasons. First, aspergillomas are rarely associated with UIP. Second, multiple aspergillomas usually occur in immunocompromised patients whereas our patient was not immunocompromised. Third, despite the bilateral distribution of honeycombing in this patient, the aspergillomas were strictly unilateral. Finally, whereas aspergillomas are usually upper lobe predominant, our patient’s aspergillomas were localized to the right lower lobe. CONCLUSIONS: Chronic aspergillomas increase the risk of local tissue invasion which may result in potentially life-threatening hemoptysis. Fortunately, this patient’s hemoptysis spontaneously resolved and she subsequently remained asymptomatic. Such a presentation should be kept in mind when taking care of similar patients. Reference #1: Kumar N, Mishra M, Singhal A, Kaur J, Tripathi V. Aspergilloma coexisting with idiopathic pulmonary fibrosis: A rare occurrence. J Postgrad Med 2013;59:145-8 Reference #2: Moodley L, Pillay J, Dheda K. Aspergilloma and the surgeon. J Thorac Dis. 2014;6(3):202-9. Reference #3: Regis Gothard Bopaka, Hasna Jabri, Wiam El Khattabi, Hicham Afif European Respiratory Journal 2015 46: PA2650; DISCLOSURES: No relevant relationships by Nina Chan, source=Web Response No relevant relationships by Peter Sloane, source=Web Response

Lactate and cancer: spinal metastases and potential therapeutic targets (part 2)

Metastatic spine disease is a heterogeneous clinical condition commonly requiring surgical intervention. Despite this heterogeneity, all cases share the common theme of altered tumor metabolism, characterized by aerobic glycolysis and high lactate production. Here we review the existing literature on lactate metabolism as it pertains to tumor progression, metastasis, and the formation of painful bone lesions. We included articles from the English literature addressing the role of lactate metabolism in the following: (I) primary tumor aggressiveness, (II) local tissue invasion, (III) metastasis formation, and (IV) generation of oncologic pain. We also report current investigations into restoring normal lactate metabolism as a means of impeding tumor growth and the formation of bony metastases. Both in vivo and in vitro experiments suggest that high lactate levels may be necessary for tumor cell growth, as small molecules inhibitors of lactate dehydrogenase (LDH5/LDHA) decrease both the rate of tumor growth and formation of metastases. Additionally, in vitro evidence strongly implicates lactate in tumor cell migration by driving the amoeboid movements of these cells. Acidification of the local bony tissue by excess lactate production activates CGRP+ neurons in the bone marrow and periosteum to generate oncologic bone pain. High lactate may also increase expression of acid sensing receptors in these neurons to generate the neuropathic pain seen in some patients with metastatic disease. Lastly, investigation into lactate-directed therapeutics is still early in development. Initial preclinical trials looking at LDH5/LDHA inhibitors as well as inhibitors of lactate transporters (MCT1) have demonstrated promise, but clinical work has been restricted to a single phase I trial. Lactate appears to play a crucial role in the pathogenesis of metastatic spine disease. Efforts are ongoing to identify small molecules inhibitors of targets in the lactogenic pathway capable of preventing the formation of osseous metastatic disease.

Clinical pattern of fungal balls in the paranasal sinuses: our experience with 70 patients.

Many physicians recommend endoscopic sinus surgery (ESS) even when an asymptomatic paranasal sinus (PNS) fungal ball is detected incidentally. The aim of this study was to investigate the natural behavior of PNS fungal balls via sinus imaging techniques. A follow-up study of 74 pathologically confirmed fungus balls was conducted in 70 patients who underwent multiple head and neck computed tomography (CT) scans or magnetic resonance imaging (MRI). We investigated the changes in symptoms and lesion size, as well as any new occurrences. Of the 74 fungus balls detected in 70 patients, we observed the renewed formation of a fungal ball in 21 patients, which was not present on initial imaging conducted over a period of 2-162 months. The fungal ball was already present in 53 patients on the initial screening, and the longest follow-up was 197 months (range 1-197 months). Of these 53 lesions, 29 lesions showed an increase in size (29/53, 54.7%), whereas 12 lesions were not associated with any clinical symptoms (12/53, 22.6%). In the 21 newly formed fungal balls, further development was observed in 10 lesions, with 4 lesions showing an increase in size. Thus, size increment occurred in 33 of the 57 fungus balls. The fungal balls can exist without local tissue invasion for up to 17years and new formation of the fungal balls was observed even within 2 months, especially when accompanied by initial clinical symptoms of sinusitis.

CHCHD2 promotes hepatocellular carcinoma and indicates poor prognosis of hepatocellular carcinoma patients.

The coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) is overexpressed in several types of cancer. This study aimed to investigate the role of CHCHD2 in hepatocellular carcinoma (HCC). The expression of CHCHD2 in HCC and non-tumorous tissues was detected by immunohistochemistry and Western blot analysis, and the correlation between CHCHD2 expression and clinicopathological features of HCC was analyzed. Furthermore, the proliferation, apoptosis and migration of HepG2 cells with CHCHD2 knockdown were examined. We found that CHCHD2 was upregulated in HCC tissues, and high CHCHD2 expression was associated with poor differentiation, lymph node metastasis, local tissue invasion, high TNM grade of HCC and poor patient survival. Depletion of CHCHD2 led to significantly reduced cell proliferation, increased apoptosis and diminished migratory capacity in HepG2 cells. In addition, HCC tissues had high expression of CD105, a microvessel marker, and HepG2 cells depleted of CHCHD2 had low CD105 expression. In conclusion, CHCHD2 may play an oncogenic role in HCC via promoting tumor cell growth and migration while preventing apoptosis. CHCHD2 is a potential biomarker for poor outcome of HCC patients.

Association of BRAF gene and TSHR with cervical lymph node metastasis of papillary thyroid microcarcinoma.

Differences in BRAF gene mutation frequency and thyroid-stimulating hormone receptor (TSHR) protein expression in thyroid tissues were detected to investigate their association with local tissue invasion and cervical lymph node metastasis potential of papillary thyroid microcarcinoma (PTMC). The BRAF gene mutation frequency and TSHR expression in PTMC patients were detected via qPCR and immunohistochemical method, and the association between them was discussed combined with the clinical and pathological parameters. Kruskal-Wallis test was used for the univariate correlation analyses and comparison of mutation rate and expression rate, and Chi-square test was used for the association of central lymph node metastasis with BRAF gene and TSHR. The BRAFV600E mutation only existed in patients with thyroid cancer. Τhe larger the number of metastatic central lymph nodes was, the higher the proportion of BRAFV600E mutation would be. Τhe BRAFV600E mutation was related to the primary lesion size, capsular infiltration and lymph node metastasis of PTMC (P<0.05). The expression of TSHR in PTMC tissues was < those in thyroid benign lesions and para-carcinoma normal tissues, which was positively associated with the central lymph node metastasis (P<0.05). Τhe low expression of TSHR was related to the primary lesion size, capsular infiltration and metastatic lymph nodes of PTMC (P<0.05). The BRAFV600E and TSHR may be involved in the occurrence and lymphatic metastasis of PTMC. The BRAFV600E mutation has no association with the TSHR protein expression (P=0.256), but the coincidence coefficient indicates that their diagnostic significance in PTMC is not similar, so BRAFV600E mutation and TSHR protein expression can be used jointly in the prediction of invasion and lymph node metastasis of PTMC, which may be more meaningful for clinical guidance.