Tumor Mass Effect Research Articles

Animal models of spontaneous pancreatic neuroendocrine tumors

Pancreatic neuroendocrine tumors (PNETs) are usually low-grade neoplasms derived from the endocrine pancreas. PNETs can be functioning and cause well-described hormonal hypersecretion syndromes or non-functioning and cause only tumor mass effect. PNETs appear to be more common recently likely due to incidental detection by imaging. Although the diagnosis and management of PNETs have been evolving rapidly, much remains to be studied in the areas of molecular pathogenesis, molecular markers of tumor behavior, early detection, and targeted drug therapy. Unique challenges facing PNETs studies are long disease course, the deep location of pancreas and difficult access to pancreatic tissue, and the variety of tumors, which make animal models valuable tools for PNETs studies. Existing animal models of PNETs have provided insights into the pathogenesis and natural history of human PNETs. Future studies on animal models of PNETs should address early tumor detection, molecular markers of tumor behavior, and novel targeted therapies.

Single-Cell Phenotypic Characterization of Human Pituitary GHomas and Non-Functioning Adenomas Based on Hormone Content and Calcium Responses to Hypothalamic Releasing Hormones.

Human pituitary tumors are generally benign adenomas causing considerable morbidity due to excess hormone secretion, hypopituitarism, and other tumor mass effects. Pituitary tumors are highly heterogeneous and difficult to type, often containing mixed cell phenotypes. We have used calcium imaging followed by multiple immunocytochemistry to type growth hormone secreting (GHomas) and non-functioning pituitary adenomas (NFPAs). Individual cells were typed for stored hormones and calcium responses to classic hypothalamic releasing hormones (HRHs). We found that GHomas contained growth hormone cells either lacking responses to HRHs or responding to all four HRHs. However, most GHoma cells were polyhormonal cells responsive to both thyrotropin-releasing hormone (TRH) and GH-releasing hormone. NFPAs were also highly heterogeneous. Some of them contained ACTH cells lacking responses to HRHs or polyhormonal gonadotropes responsive to LHRH and TRH. However, most NFPAs were made of cells storing no hormone and responded only to TRH. These results may provide new insights on the ontogeny of GHomas and NFPAs.

Pituitary Gigantism - Experience of a Single Center from Western India

Limited data are available on pituitary gigantism, as it is a rare disorder. This study was carried out to assess the clinical, hormonal, and radiologic profiles and management outcomes of patients with pituitary gigantism. We conduced a retrospective analysis of 14 patients with pituitary gigantism who presented to a single tertiary care institute from 1990 to 2014. Thirteen patients were male, and 1 was female. The mean age at diagnosis was 21.9 ± 6.1 years, with a mean lag period of 6.5 ± 5.6 years. The mean height SD score at the time of diagnosis was 3.2 ± 0.6. Symptoms of tumor mass effect were the chief presenting complaint in the majority (50%) of patients, while 2 patients were asymptomatic. Six patients had hyperprolactinemia. At presentation, the nadir PGGH (postglucose GH) and insulin-like growth factor (IGF 1)-ULN (× upper limit of normal) were 63.2 ± 94.9 ng/mL and 1.98 ± 0.5, respectively. All (except 1 with mild pituitary hyperplasia) had pituitary macroadenoma. Six patients had invasive pituitary adenoma. Transsphenoidal surgery (TSS) was the primary modality of treatment in 13/14 patients, and it achieved remission in 4/13 (30.76%) patients without recurrence over a median follow-up of 7 years. Post-TSS radiotherapy (RT) achieved remission in 3/5 (60%) patients over a median follow-up of 3.5 years. None of the patients received medical management at any point of time. Gigantism is more common in males, and remission can be achieved in the majority of the patients with the help of multimodality treatment (TSS and RT).

Recent advances in management of phaeochromocytoma

Pheochromocytoma (PCC) and paraganglioma (PGL) are the neuroendocrine tumours that arise in adrenal medulla or extra adrenal sympathetic and parasympathetic paraganglia. Paraganglia are small organs that mainly consist of neuroendocrine cells derived from the embryonic neural crest that have the ability to synthesize and secrete catecholamines. Sympathetic PGLs are usually located in the chest, abdomen, or pelvis while parasympathetic PGLs are distributed along parasympathetic nerves in the head, neck, and upper mediastinum, also referred to as head and neck PGL (HNP). PCC/PGLs can be either functional (sympathetic) or non-functional (parasympathetic) based on catecholamine synthesis and secretion. In children diagnosed with hypertension, up to 1.7% have a catecholamine-secreting neoplasm. The majority of these tumours in childhood are PCC/PGLs. Incidence rates of PCC/PGLs are estimated at 0.3 cases per million per year or less. Approximately 10 –20% of these cases are diagnosed during childhood. Approximately half of the apparently sporadic PCC/PGLs that present in patients younger than 18 years are due to an identifiable germline mutation and this increases up to 70% in children less than 10 years of age. Hereditary tumor syndromes associated with PCC include Von Hippel-Lindau (VHL) disease, multiple endocrine neoplasia 2 (MEN-2), the familial PGL syndromes and rarely, neurofibromatosis (NF) type 1. Recently, many other genes are found to be involved in pathogenesis of PCC/PGLs. Hereditary PCC/PGLs are often multifocal and, in the case of PCC, frequently bilateral. Children usually present becauseof symptomatic catecholamine hypersecretion or, less often, due to tumor mass effects (e.g. pain), or as an incidental radiographic finding, or because of family screening. At present, the diagnostic test of choice is the measurement of fractionated plasma and/or urine metanephrines (metanephrines and normetanephrines). A four-fold increase above the reference range is associated with an almost 100% probability of the presence of a catecholamine-secreting tumor. 123I-metaiodobenzylguanidine(MIBG) is a highly specific test that can confirm the catecholamine-secreting nature of a tumor, localize tumors not seen with cross-sectional imaging, and identify other sites of disease as well as metastasis. Because MIBG testingis not 100% sensitive, particularly in some genetic mutations, recently other functional scans have been studied in the evaluation of PCC/PGL: 18F fluorodihydroxyphenylalanine (DOPA) positron emission tomography (PET), 18F fluorodopamine (FDA) PET,18F fluorodeoxyglucose (FDG) PET. Surgical resection is the mainstay in the treatment of PCC/PGLs. It should be done after adequate alfa and beta adrenergic blockade to minimize the hemodynamic fluctuation during surgery. Laparoscopic adrenalectomy is the preferred procedure for most PCC. Laparotomy should be considered in patients with large PCC and/or a concern for underlying malignancy based upon the clinical presentation or radiographic appearance of the tumor. In the setting of bilateral PCC, cortical-sparing procedures should be considered for the adrenal with the least tumor bulk. The cortical-sparing approach is particularly attractive in young children and children at risk for noncompliance with lifelong glucocorticoid and mineralocorticoid replacement. The surgical approach for removal of a PGL depends upon the location of the tumor but in selected cases can also be performed laparoscopically. Patients with unresectable malignant tumors or distant metastatic disease can usually be treated symptomatically with adrenergic blockade. Radiation therapy or radiofrequency ablation can help with symptomatic metastatic disease, and IV bisphosphonates can be considered bony metastases, particularly in patients with bone pain or lesions that increase the risk of pathological fracture. Systemic treatment modalities are only palliative in nature and include 123I-MIBG therapy, peptide receptor radiotherapy (PRRT) and chemotherapy. PCC/PGLs can have unpredictable behavior and metastasize late in the clinical course. In addition, children in particular are at risk for the development of metachronous tumors. This makes long-term follow-up mandatory in children with PCC/PGL.

Pancreatic Tumor Growth Prediction with Multiplicative Growth and Image-Derived Motion.

Pancreatic neuroendocrine tumors are abnormal growths of hormone-producing cells in the pancreas. Different from the brain in the skull, the pancreas in the abdomen can be largely deformed by the body posture and the surrounding organs. In consequence, both tumor growth and pancreatic motion attribute to the tumor shape difference observable from images. As images at different time points are used to personalize the tumor growth model, the prediction accuracy may be reduced if such motion is ignored. Therefore, we incorporate the image-derived pancreatic motion to tumor growth personalization. For realistic mechanical interactions, the multiplicative growth decomposition is used with a hyperelastic constitutive law to model tumor mass effect, which allows growth modeling without compromising the mechanical accuracy. With also the FDG-PET and contrast-enhanced CT images, the functional, structural, and motion data are combined for a more patient-specific model. Experiments on synthetic and clinical data show the importance of image-derived motion on estimating physiologically plausible mechanical properties and the promising performance of our framework. From six patient data sets, the recall, precision, Dice coefficient, relative volume difference, and average surface distance were 89.8 ± 3.5%, 85.6 ± 7.5%, 87.4 ± 3.6%, 9.7 ± 7.2%, and 0.6 ± 0.2 mm, respectively.

Signaling pathways regulating pituitary lactotrope homeostasis and tumorigenesis.

Dysregulation of the signaling pathways that govern lactotrope biology contributes to tumorigenesis of prolactin (PRL)-secreting adenomas, or prolactinomas, leading to a state of pathological hyperprolactinemia. Prolactinomas cause hypogonadism, infertility, osteoporosis, and tumor mass effects, and are the most common type of neuroendocrine tumor. In this review, we highlight signaling pathways involved in lactotrope development, homeostasis, and physiology of pregnancy, as well as implications for signaling pathways in pathophysiology of prolactinoma. We also review mutations found in human prolactinoma and briefly discuss animal models that are useful in studying pituitary adenoma, many of which emphasize the fact that alterations in signaling pathways are common in prolactinomas. Although individual mutations have been proposed as possible driving forces for prolactinoma tumorigenesis in humans, no single mutation has been clinically identified as a causative factor for the majority of prolactinomas. A better understanding of lactotrope-specific responses to intracellular signaling pathways is needed to explain the mechanism of tumorigenesis in prolactinoma.

Management of advanced plexiform neurofibromatosis of the foot presenting with skeletal deformation and intractable pain: An indication for proximal amputation

Plexiform neurofibromas of the foot are rare and often present with significant pain, deformity, and functional impairment secondary to their locally invasive behavior. While treatment has traditionally focused on attempts at radical resection, a lack of consensus among surgeons has hindered the establishment of a well-defined algorithm to guide the management of these highly co-morbid peripheral nerve sheath tumors. We present the case of an advanced plexiform neurofibroma of the right foot in a 24-year-old male with neurofibromatosis type 1. The patient presented following accelerated tumor growth with extensive osseous erosion, intractable pain, and progressive ankle instability that limited his capacity to ambulate and wear shoes. A modified transtibial amputation with a vascularized fibular bone graft (Ertl procedure) was performed without complication. Following graduated rehabilitation, postoperatively, the patient regained functional independence and was able to ambulate without pain in a customized prosthesis after 3 months. Plexiform neurofibromas of the foot present a complex challenge for foot and ankle surgeons. On the basis of our experience and previously reported cases, we advocate for amputation over aggressive attempts at advanced limb salvage for patients with extensive skeletal destruction, joint instability, and/or intractable pain caused by tumor mass effect.

Pheochromocytomes et paragangliomes pédiatriques: revue de la littérature

Pheochromocytomas and paragangliomas (PHEO/PGL) are neuroendocrine tumors that arise from sympathetic and parasympathetic paraganglia. Although well describedin the adult population, diagnosis and treatment of these exceptionally rare neoplasms remains poorly characterized in children. This article reviews recent advances in clinical presentation, genetics, biochemistry, imaging and treatment of children with benign or malignant PHEO/PGL. Compared to adults, pediatric PHEO/PGL are more frequently familial, bilateral, multifocal and malignant. Approximately 50% of pediatric PHEO/PGLare associated with a mutationof one of the 12 known susceptibility genes. Von Hippel-Lindau disease, type 1 neurofibromatosis, type 2 multiple endocrine neoplasia and familial PGL syndrome are hereditary tumor syndromes associated with an increased risk of developing such diseases. Clinical presentation includes symptoms related to catecholamine hypersecretion and/or tumor mass effect. Plasma and/or urine metanephrine dosages are recommended as first-line diagnostic biochemical tests. Magnetic resonance imaging is useful asinitial radiological approach. Most pediatric PHEO/PGLs are benign. Surgical resection, with appropriate perioperative management of catecholamine-related symptoms, remains the treatment of choice. In case of metastatic disease, surgical removal of metastases when possible and I-131-MIBG radiotherapy provide limited results whereas chemotherapy is reserved for more advanced stages.

Crossed cerebrocerebellar language lateralization: an additional diagnostic feature for assessing atypical language representation in presurgical functional MR imaging.

Determining language dominance with fMRI is challenging in patients with brain tumor, particularly in cases of suspected atypical language representation. Supratentorial activation patterns must be interpreted with great care when the tumor is in or near the presumed language areas, where tumor tissue or mass effect can lead to false-negative fMRI results. In this study, we assessed cerebrocerebellar language fMRI lateralization in healthy participants and in patients with brain tumors with a focus on atypical language representation. Twenty healthy participants and 38 patients with a brain tumor underwent fMRI with a verb-generation task. Cerebral and cerebellar language lateralizations were separately classified as left-sided, right-sided, or symmetric. Electrocortical stimulation was performed in 19 patients. With the McNemar test, we evaluated the dependency between language lateralization in the cerebrum and cerebellum, and with Pearson correlation analysis, the relationship between the cerebral and cerebellar lateralization indices. There was a significant dependency between cerebral and cerebellar language activation, with moderate negative correlation (Pearson r = -0.69). Crossed cerebrocerebellar language activation was present in both healthy participants and patients, irrespective of handedness or typical or atypical language representation. There were no discordant findings between fMRI and electrocortical stimulation. Language lateralization in the cerebellum can be considered an additional diagnostic feature to determine language dominance in patients with brain tumor. This is particularly useful in cases of uncertainty, such as the interference of a brain tumor with cerebral language activation on fMRI and atypical language representation.

Reoperation for recurrent high-grade glioma: a current perspective of the literature.

Optimal treatment for recurrent high-grade glioma continues to evolve. Currently, however, there is no consensus in the literature on the role of reoperation in the management of these patients. In this analysis, we reviewed the literature to examine the role of reoperation in patients with World Health Organization grade III or IV recurrent gliomas, focusing on how reoperation affects outcome, perioperative complications, and quality of life. An extensive literature review was performed through the use of the PubMed and Ovid Medline databases for January 1980 through August 2013. A total 31 studies were included in the final analysis. Of the 31 studies with significant data from single or multiple institutions, 29 demonstrated a survival benefit or improved functional status after reoperation for recurrent high-grade glioma. Indications for reoperation included new focal neurological deficits, tumor mass effect, signs of elevated intracranial pressure, headaches, increased seizure frequency, and radiographic evidence of tumor progression. Age was not a contraindication to reoperation. Time interval of at least 6 months between operations and favorable performance status (Karnofsky Performance Status score ≥70) were important predictors of benefit from reoperation. Extent of resection at reoperation improved survival, even in patients with subtotal resection at initial operation. Careful patient selection such as avoiding those individuals with poor performance status and bevacizumab within 4 weeks of surgery is important. Although limited to retrospective analysis and patient selection bias, mounting evidence suggests a survival benefit in patients receiving a reoperation at the time of high-grade glioma recurrence.

SU‐E‐J‐122: Detecting Treatment‐Induced Metabolic Abnormalities in Craniopharyngioma Patients Undergoing Surgery and Proton Therapy

Purpose:To identify treatment‐induced defects in the brain of children with craniopharyngioma receiving surgery and proton therapy using fluorodeoxyglucose positron emission tomography (FDG PET).Methods:Forty seven patients were enrolled on a clinical trial for craniopharyngioma with serial imaging and functional evaluations. Proton therapy was delivered using the double‐scattered beams with a prescribed dose of 54 Cobalt Gray Equivalent. FDG tracer uptake in each of 63 anatomical regions was computed after warping PET images to a 3D reference template in Talairach coordinates. Regional uptake was deemed significantly low or high if exceeding two standard deviations of normal population from the mean. For establishing the normal ranges, 132 children aged 1–20 years with noncentral nervous system related diseases and normal‐appearing cerebral PET scans were analyzed. Age‐ and gender‐dependent regional uptake models were developed by linear regression and confidence intervals were calculated.Results:Most common PET abnormality before proton therapy was significantly low uptake in the frontal lobe, the occipital lobe (particularly in cuneus), the medial and ventral temporal lobe, cingulate gyrus, caudate nuclei, and thalamus. They were related to injury from surgical corridors, tumor mass effect, insertion of a ventricular catheter, and the placement of an Ommaya reservoir. Surprisingly a significantly high uptake was observed in temporal gyri and the parietal lobe. In 13 patients who already completed 18‐month PET scans, metabolic abnormalities improved in 11 patients from baseline. One patient had persistent abnormalities. Only one revealed new uptake abnormalities in thalamus, brainstem, cerebellum, and insula.Conclusion:Postoperative FDG PET of craniopharyngioma patients revealed metabolic abnormalities in specific regions of the brain. Proton therapy did not appear to exacerbate these surgery‐ and tumor‐induced defects. In patients with persistent and new abnormalities, continued investigation on clinical symptoms and cognitive outcomes is ongoing to establish the association and predictive values of metabolic imaging.

Percutaneous image-guided ablation of bone and soft tissue tumours: a review of available techniques and protective measures.

BackgroundPrimary or metastatic osseous and soft tissue lesions can be treated by ablation techniques.MethodsThese techniques are classified into chemical ablation (including ethanol or acetic acid injection) and thermal ablation (including laser, radiofrequency, microwave, cryoablation, radiofrequency ionisation and MR-guided HIFU). Ablation can be performed either alone or in combination with surgical or other percutaneous techniques.ResultsIn most cases, ablation provides curative treatment for benign lesions and malignant lesions up to 3 cm. Furthermore, it can be a palliative treatment providing pain reduction and local control of the disease, diminishing the tumour burden and mass effect on organs. Ablation may result in bone weakening; therefore, whenever stabilisation is undermined, bone augmentation should follow ablation depending on the lesion size and location.ConclusionThermal ablation of bone and soft tissues demonstrates high success and relatively low complication rates. However, the most common complication is the iatrogenic thermal damage of surrounding sensitive structures. Nervous structures are very sensitive to extremely high and low temperatures with resultant transient or permanent neurological damage. Thermal damage can cause normal bone osteonecrosis in the lesion’s periphery, surrounding muscular atrophy and scarring, and skin burns. Successful thermal ablation requires a sufficient ablation volume and thermal protection of the surrounding vulnerable structures.Teaching points• Percutaneous ablations constitute a safe and efficacious therapy for treatment of osteoid osteoma.• Ablation techniques can treat painful malignant MSK lesions and provide local tumour control.• Thermal ablation of bone and soft tissues demonstrates high success and low complication rates.• Nerves, cartilage and skin are sensitive to extremely high and low temperatures.• Successful thermal ablation occasionally requires thermal protection of the surrounding structures.

Pediatric MRI of the Brain: A Primer

1. Kamakshya P. Patra, MD* 2. Jeffrey D. Lancaster, MD* 3. Jeffery Hogg, MD† 4. Jeffrey S. Carpenter, MD† 1. *Department of Pediatrics, Section of Hospital Pediatrics, West Virginia University Children’s Hospital, Morgantown, WV. 2. †Department of Neuroradiology, West Virginia University Health Sciences Center, Morgantown, WV. * Abbreviations: ADHD: : attention-deficit/hyperactivity disorder CSF: : cerebrospinal fluid CT: : computed tomography DWI: : diffusion-weighted magnetic resonance imaging FLAIR: : fluid-attenuated inversion recovery fMRI: : functional magnetic resonance imaging MRI: : magnetic resonance imaging MRV: : magnetic resonance venography NAA: : N -acetylaspartate SDH: : subdural hematoma Because of recent advances in magnetic resonance imaging (MRI) techniques, pediatricians should be aware of the different modalities and their unique advantages and appropriateness in different clinical situations. After completing this article, readers should be able to: 1. Understand the pros and cons of MRI and computed tomography of the brain. 2. Know the basic principles of MRI and its different image modalities. 3. Be aware of the appropriateness of different modalities in specific clinical situations. Magnetic resonance imaging (MRI) is based on the absorption and emission of radiofrequency energy by hydrogen protons whose spin is influenced by changing magnetic fields (0.3 to 1.5 T). Unlike computed tomography (CT), there is no radiation exposure. T1-weighted images cause fat (eg, myelin in white matter) to appear bright and water (eg, cerebrospinal fluid [CSF] or edema) to appear dark on this sequence. The gray-white interfaces of the brain are well depicted on these sequences, especially if with the images are thinly sliced. T2-weighted images cause water (eg, CSF and edema) to appear bright and fat to appear dark. The MRI-based intravenous contrast agents (eg, gadolinium) are frequently used in T1-weighted images (Fig 1A and B) to make serum appear bright. The blood-brain barrier typically serves to limit the passage of many molecules out of the blood vessels. If disease processes break down this barrier (such as infection, tumors, or inflammation), intravenous contrast agents can cross into the brain, causing areas of contrast entry to appear very bright. Figure 1. T1-weighted image at the level of midbrain. A. The cerebrospinal fluid (CSF) appears dark. B. The CSF appears bright. Note the gray and white matter differentiation …

Maximum Safe Resection of Glioblastoma Multiforme

Maximum Safe Resection of Glioblastoma Multiforme

Association of baseline health and gender with small renal mass pathology.

515 Background: Previous reports describe that 20% of small renal masses (SRM) are benign and women are twice as likely to have benign pathology. In this study we further explore the association of baseline health and gender with SRM pathology. Methods: After IRB approval, retrospective chart review of patients who have undergone nephrectomy at Memorial Sloan-Kettering Cancer Center from 05/1998 to 10/2012 with final path ≤ 4cm and staged as pT1a if malignant. Tumor size ≤ 4cm was chosen to limit the tumor mass effect on renal function. Patients with solitary kidney, multiple and bilateral tumors, and history of prior renal surgeries were excluded. Collected data included age, gender, race, ASA class for medical co−morbidities which were divided into low (I−II) and high (III−IV), procedure, preoperative serum creatinine, eGFR, and final pathology. eGFR was calculated using the CKD−Epi formula. Preoperative Chronic kidney disease (pCKD) was defined as eGFR < 60 mL/min per 1.73 m2. Malignant pathologies were clear cell renal cell carcinoma (RCC), papillary RCC and chromophobe RCC whereas benign were oncocytoma, angiomyolipoma and other. Logistic regression analysis was performed to determine clinical factors associated with malignant SRM. Results: Our cohort consisted of 1726 patients with mean age 59.7 yrs. 61% (n=1045) were men, 90% (n=1,553) were white, 43% (n=736) had high ASA, 89% (1,540) underwent partial nephrectomy, 30% (n=525) had pCKD, 83% (n=1426) with malignant pathology and mean tumor size 2.5cm. On bivariable analysis patients with malignant SRM had a higher proportion of men (64.3 vs. 42.7%, p<0.001), high ASA class (43.8 vs. 37.3%, p=0.041) and larger tumors (2.6 vs. 2.3, p<0.001). There were no differences in age, race, mean eGFR or proportion with pCKD. On logistic regression analysis by gender factors associated with malignant pathology in women were high ASA class (OR 1.57, 95% CI 1.07−2.32) and tumor size (OR 1.48, 95% CI 1.20−1.81), and in men tumor size only (OR 1.33, 95% CI 1.06−1.67). Conclusions: Our results are in line with previous reports on the association of male gender and larger tumor size with malignant SRM. In addition we do show that among women those with poor health have a higher likelihood for having a malignant SRM.

Chapter 23 - Familial pituitary tumors

Pituitary adenomas are benign intracranial neoplasms that present a major clinical concern due to hormone overproduction and/or tumor mass effects. The majority of pituitary adenomas occur sporadically; however, familial cases are increasingly being recognized, such as multiple endocrine neoplasia type 1 (MEN1), Carney complex (CNC), and familial isolated pituitary adenoma (FIPA). Familial pituitary tumors appear to differ from their sporadic counterparts both in their genetic basis and in clinical characteristics. Evidence suggests that, especially in MEN1 and FIPA, tumors are more aggressive and affect patients at a younger age, therefore justifying the importance of early diagnosis, while in Carney complex pituitary hyperplasia is common. The genetic alterations responsible for the formation of familial pituitary syndromes include the MEN1 gene, responsible for about 80% of MEN1 cases, the regulatory subunit of the protein kinase A, PRKAR1A, responsible for about 70% of Carney complex cases, and AIP, the gene coding the aryl hydrocarbon receptor interacting protein, responsible for about 20% of FIPA cases. Rarely other genes have also been found responsible for familial pituitary adenoma cases. McCune-Albright syndrome (MAS) also has a genetic origin due to mosaic mutations in the G protein-coupled α subunit coded by the GNAS1 gene. In this chapter, we summarize the genetic and clinical characteristics of these familial pituitary syndromes and MAS.

The neurobiology of oral cancer pain

Oral cancer pain is more severe, on average, than pain from any other cancer. The public health problem of cancer pain is, ironically, exacerbated by improved chemo- and radio-therapies that prolong survival. The intensity of oral cancer pain escalates with disease progression; terminal patients generally experience debilitating pain during their final months of life. The etiology of oral cancer pain is not known and current treatment is ineffective. Cancer pain is hypothesized to result from a tumor-mass effect and/or activation of primary afferent nociceptors by mediators liberated by the cancer. Dr. Schmidt discussed the molecular cross-talk between cancer and peripheral nervous system that might responsible for pain. He presented data demonstrating a reciprocal proliferative effect between cancer and surrounding sensory nerves.

Mixed Acinar-Endocrine Carcinoma of the Pancreas

The objective of this study was to characterize the novel clinical and pathological features of mixed acinar-endocrine carcinoma of the pancreas. This was a retrospective review of medical records and surgical pathology specimens of patients with a diagnosis of mixed acinar-endocrine carcinoma of the pancreas at Cedars-Sinai Medical Center between 2005 and 2011. Additional immunohistochemistry was performed on the specimens of some patients. Five patients were identified. The median age at presentation was 74 years (range, 59-89 years), and all patients were male. The presenting symptoms were all related to tumor mass effects. The median size of the tumor was 10 cm (range, 3.9-16 cm). Preoperative clinical diagnosis aided by fine-needle aspiration biopsy was incorrect in all 5 cases. Most tumors (3/5) exhibited predominantly endocrine differentiation without hormonal production. Only 10% to 30% of cells were truly amphicrine, whereas most were differentiated into either endocrine or acinar phenotype. The clinical behavior ranged from moderate to aggressive with postoperative survival from 2.5 months to more than 3 years. Four patients received neoadjuvant or adjuvant chemotherapy with variable responses. Mixed acinar-endocrine carcinoma of the pancreas appears to be not uncommon in men, may harbor predominantly endocrine component, is often misdiagnosed by cytology, and exhibits variable clinical behavior. Mixed acinar-endocrine carcinoma of the pancreas should be considered in older patients with sizable pancreatic mass and may warrant aggressive surgical resection and chemotherapy.

Anaplastic Astrocytoma

Standard treatment of anaplastic astrocytoma (AA) in good performance patients consists of maximal safe surgical resection followed by focal, fractionated, external beam radiotherapy (RT) alone or in combination with concurrent and adjuvant temozolomide (TMZ). Since prospective data regarding the use of chemoradiotherapy for AA is lacking, the practice is based on the extrapolation of results from a randomized study in glioblastoma (GB). Whether the data from the GB study can and should be extrapolated is controversial, although a large multicenter, randomized, phase III study is underway to define optimal initial AA treatment. Patients should be tapered off corticosteroids completely or to the lowest dose necessary to treat neurologic dysfunction. Anti-epileptic drugs (AED) are not indicated unless there is a history of seizure; levetiracetam is the preferred AED in malignant glioma (MG). Unless there is evidence of intracranial hemorrhage, venous thromboembolism (VTE) should be treated with low-molecular-weight heparin (LMWH) therapy. At recurrence, patients with good performance status are usually treated with cytotoxic chemotherapy following, or in lieu of, repeat surgery. TMZ is the preferred chemotherapeutic agent in patients without prior exposure; lomustine is recommended for tumors resistant to TMZ. In patients with neurologic dysfunction secondary to tumor edema and mass effect who are not amenable to surgery, the use of bevacizumab is associated with improved neurologic function and better quality of life. Given the limited treatment options at tumor recurrence, consideration for enrollment on a clinical trial is encouraged.

MAGNETIC RESONANCE IMAGING FEATURES OF INTRACRANIAL GRANULAR CELL TUMORS IN SIX DOGS

Magnetic resonance (MR) imaging characteristics of intracranial granular cell tumors (GCTs) have been previously reported in three dogs. The goal of this retrospective study was to examine a larger number of dogs and determine whether distinctive MR characteristics of intracranial GCTs could be identified. Six dogs with histologically confirmed intracranial GCTs and MR imaging were included. Tumor location, size, mass effect, T1- and T2-weighted signal intensity, and peritumoral edema MR characteristics were recorded. In all dogs, GCTs appeared as well-defined, extra-axial masses with a plaque-form, sessile distribution involving the meninges. All tumors were located along the convexity of the cerebrum, the falx cerebri, or the ventral floor of the cranial vault. All tumors were mildly hyperintense on T1-weighted images, and iso- to hyperintense on T2-weighted images. A moderate-to-severe degree of peritumoral edema and mass effect were evident in all dogs. Findings indicated that, while several MR imaging characteristics were consistently identified in canine cerebral GCTs, none of these characteristics were unique or distinctive for this tumor type alone.