Malignant Peripheral Nerve Sheath Tumor: molecular pathogenesis and current management considerations

Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are rare tumors that often occur in patients with neurofibromatosis 1. Surgical resection represents the mainstay of treatment. Radiation and chemotherapy have a role in selected patients with MPNST. Accurate pathologic diagnosis remains a challenge in many cases of MPNST. There are many recent advances in the understanding of the molecular pathogenesis of MPNST which represent the best opportunities to develop new strategies for management of patients with MPNST.     

Richter syndrome: pathogenesis and management

Richter syndrome (RS) is the development of an aggressive lymphoma in patients with a previous or concomitant diagnosis of chronic lymphocytic leukemia (CLL). The incidence rate RS is ~0.5% per year of observation. Two biomarkers (NOTCH1 mutations and subset 8 configuration of the B-cell receptor) may help identifying CLL patients at risk of RS to be considered for close monitoring and a careful biopsy policy. In the presence of clinical features suspicious of RS, diagnosis of transformation and choice of the site of biopsy may take advantage of fluorine 18 fluorodeoxyglucose (¹⁸FDG) positron emission tomography (PET)/computed tomography (CT). Molecular lesions of regulators of tumor suppression (TP53), cell cycle (CDKN2A), and cell proliferation (NOTCH1, MYC) overall account for ~90% of RS and may be responsible for the aggressive clinical phenotype observed in this disease because of the combined effect of chemoresistance and rapid disease kinetics. The prognosis of RS is generally highly unfavorable. However, the pattern of survival is not homogeneous and the most important prognostic factor is the clonal relationship between the CLL and the aggressive lymphoma clones. Rituximab-containing polychemotherapy represents the backbone for induction treatment in RS. Younger patients who respond to induction therapy should be offered stem cell transplant (SCT) to prolong survival.     

恶性肿瘤相关凝血功能紊乱与抗凝治疗

凝血功能紊乱与恶性肿瘤之间相互影响、相互促进,最终形成一个严重影响肿瘤患者预后的恶性循环.凝血功能紊乱与恶性肿瘤相互作用关系的日趋明朗使抗凝成为肿瘤治疗的一个新的突破口.大量实验室及临床研究显示,抗凝治疗能抑制肿瘤发生、发展,改善肿瘤患者的预后.但针对不同患者、不同种类的抗凝剂,抗凝治疗的有效性及安全性尚有待进一步深入的研究.     

Pituitary adenomas: their pathogenesis and recent management

Journal of Neuro-Oncology -     

Tumor-related epilepsy: epidemiology,pathogenesis and management

The goal of this study is to spatially discriminate tumor from treatment effect (TE), within the contrast-enhancing lesion, for brain tumor patients at all stages of treatment. To this end, the diagnostic accuracy of MRI-derived diffusion and perfusion parameters to distinguish pure TE from pure glioblastoma (GBM) was determined utilizing spatially-correlated biopsy samples. From July 2010 through June 2015, brain tumor patients who underwent pre-operative DWI and DSC-MRI and stereotactic image-guided biopsy were considered for inclusion in this IRB-approved study. MRI-derived parameter maps included apparent diffusion coefficient (ADC), normalized cerebral blood flow (nCBF), normalized and standardized relative cerebral blood volume (nRCBV, sRCBV), peak signal-height (PSR) and percent signal-recovery (PSR). These were co-registered to the Stealth MRI and median values extracted from the spatially-matched biopsy regions. A ROC analysis accounting for multiple subject samples was performed, and the optimal threshold for distinguishing TE from GBM determined for each parameter. Histopathologic diagnosis of pure TE (n?=?10) or pure GBM (n?=?34) was confirmed in tissue samples from 15 consecutive subjects with analyzable data. Perfusion thresholds of sRCBV (3575; SN/SP% = 79.4/90.0), nRCBV (1.13; SN/SP% = 82.1/90.0), and nCBF (1.05; SN/SP% = 79.4/80.0) distinguished TE from GBM (P?<?0.05), whereas ADC, PSR, and PH could not (P?>?0.05). The thresholds for CBF and CBV can be applied to lesions with any admixture of tumor or treatment effect, enabling the identification of true tumor burden within enhancing lesions. This approach overcomes current limitations of averaging values from both tumor and TE for quantitative assessments.     

Axillary web syndrome: Incidence,pathogenesis, and management

Axillary web syndrome (AWS) refers to the development of fibrotic bands or “cords” in the axilla of patients who have undergone axillary lymph node dissection for breast cancer. We review the incidence, pathogenesis, risk factors, and management of AWS. AWS is a common complication in patients who undergo axillary lymph node dissection. Even though AWS is self-limited in most cases, it causes significant morbidity. The optimal management of AWS is unclear but physiotherapy appears to be beneficial. The widespread use of less invasive procedures to evaluate the presence of metastasis in the axillary lymph nodes (ie, sentinel lymph node biopsy) is expected to reduce the incidence of AWS. The close collaboration of surgeons, oncologists, and physiotherapists is necessary for the prevention and management of this frequent condition.     

Osteoporosis due to cancer treatment: pathogenesis and management.

Many therapeutic regimens in cancer treatment carry the risk of causing or favoring the development of osteoporosis. Therapies in which hypogonadism may occur are most relevant in this respect. Prompt hormone replacement therapy is indicated in these patients. In patients in whom this is undesirable because of a hormone-dependent tumor, the risk of osteoporosis should be assessed by means of osteodensitometry, and prophylactic or therapeutic measures should be instituted if necessary. Early intervention improves outcome because osteoporosis therapy is most effective in preventing deterioration of bone mass. There remains much uncertainty in assessing the risk of combination chemotherapy with regard to the development of osteoporosis. Negative effects on the skeleton have, however, been demonstrated for individual drugs, such as methotrexate and ifosfamide. Negative effects of the tumor itself on bone metabolism may aggravate the degree of osteoporosis. Detailed data and long-term experience to assess the risk are urgently needed in this area and constitute an important research topic for the coming years and decades. This review discusses the most prevalent mechanisms of osteoporosis caused by cancer treatment and outlines therapeutic strategies for the prevention and treatment of therapy-induced bone loss.     

Tumor-associated edema in brain cancer patients: pathogenesis and management

The long-term treatment of peritumoral edema remains a major challenge in clinical neuro-oncology. Steroids have been and will remain the backbone of any anti-edematous therapy because of their striking activity, convenient oral administration and also because of their cost–effectiveness. Their side effects, however, can compromise quality of life, particularly upon continuous administration. Therapeutic alternatives which may replace or – at least – help to reduce the steroid dose are limited. However, with the development of new agents such as corticorelin acetate, there is a hope that steroid-induced side effects can be delayed and reduced. The administration of anti-angiogenic agents with steroid-sparing effects, for example, bevacizumab, is limited due to their costs. Increased knowledge on boswellic acids and cyclooxygenase-2 inhibitors which are available for clinical application may help to exploit their anti-edema activity more efficiently in the future.     

Malignant fibrous histiocytoma: an institutional review

Background: A thorough understanding of malignant fibrous histiocytoma (MFH), the most common subtype of soft tissue sarcoma, will lead to improved histologic-specific protocols. Methods: 126 patients with histologically confirmed MFH were analyzed. The median follow-up was 42 months (range 1-233 months). Results: Overall survival was 58% at 5 years and 38% at 10 years. Grade significantly influenced prognosis, with 10-year survival of 90%, 60%, and 20% for low, intermediate, and high grade tumors, respectively (p = 0.0007). Distant metastases at initial presentation (p = 0.0002) and size of the primary tumor (p = 0.0007) influenced outcome. Neither anatomic site nor depth of the primary tumor were significant prognostic factors. Positive microscopic margins were associated with a decreased disease-free survival (p = 0.006). Conclusions: Tumor grade, size, and distant metastases at initial presentation remain the most important prognostic factors for MFH. Resection with negative microscopic margins decreased the incidence of local recurrence.     

Aggressive basal cell carcinoma: Presentation, pathogenesis, and management

Basal cell carcinoma (BCC) is the most common cutaneous skin malignancy. BCC generally has a clinical course characterized by slow growth, minimal soft tissue invasiveness, and a high cure rate. Occasionally, however, BCC behaves aggressively with deep invasion, recurrence, and potential regional and distant metastasis. Several factors, including tumor size, duration, histology, and perineural spread, have been postulated as markers of the aggressive BCC phenotype. It is undetermined whether intrinsic biological factors within certain subsets of BCC predispose these tumors toward an inherently aggressive behavior, or whether any BCC with inadequate early management may assume this phenotype. Review of the pertinent literature on this topic suggests that both intrinsic biological factors and extrinsic management factors play a role in the development and progression of aggressive BCC.     

Late radiation-related fibrosis: pathogenesis,manifestations, and current management

Radiation-induced fibrosis (RIF) represents one of the most common long-term adverse effects of curative radiotherapy. Current cancer treatment approaches, involving more intensive radiotherapy regimens, used in combination with systemic agents, will likely be associated with a higher incidence and greater degree of damage to normal tissues, especially RIF. Traditionally, the development of fibrosis after radiation therapy has been considered static and irreversible. Contemporary understanding recognizes RIF as a continuum of responses mediated by molecular pathways that may be amenable to interventions. Preliminary evidence suggests that pharmacological or other interventions may be possible to reverse the manifestation of the injury and restore function to tissues. A variety of strategies have been tested for the management of RIF, although formal trials of these therapies that permit treatment comparisons are unavailable at this time. It is critical that we formally evaluate new management approaches for RIF with larger patient accrual. To this end, it is also important to develop a means of registering its occurrence for outcome analysis and to refer these patients to colleagues familiar with optimal management and enrollment in clinical trials.     

口腔化学感受器瘤的恶性生物学行为及临床处理

目的:探讨口腔化学感受器瘤的恶性生物学行为。方法:追踪分析1例口腔舌部化学感受器瘤患者临床资料及组织病理特点,总结其恶性生物学行为。结果:发生于口腔化学感受器瘤较发生于身体其它部位(颈动脉体)更容易表现出恶性生物学特性,恶性生物学行为主要表现为肿瘤浸润,包膜不清楚,手术后出现原位肿瘤复发及远处(肺部)转移。结论:对于口腔的化学感受器瘤应根据其临床特点结合细胞学特征确定生物学行为并做相应临床处理。     

Interstitial lung disease in the elderly: pathogenesis, diagnosis and management

Advancing age is associated with increased risk for some forms of interstitial lung disease (ILD), and this risk is especially reflected by the considerably increased incidence of idiopathic pulmonary fibrosis (IPF) in the elderly. Although the causes of this increased risk are not well-defined, both ageing and IPF have been associated with shortening of telomeres due to telomerase deficiency. Thoracic imaging with high-resolution computed tomographic (HRCT) scanning plays a key role in the diagnosis of ILD in the elderly, and a characteristic appearance of the lung parenchymal changes on HRCT may provide a confident diagnosis and obviate the need for invasive testing such as surgical lung biopsy. An effective treatment for IPF remains elusive, but many patients will benefit from supportive care and treatment of various co-morbid conditions that are often found in patients with IPF.     

Malignant Psoas Syndrome: Recognition of an Oncologic Entity

From January 1985 to January 1989 four patients with advanced cancer developed a syndrome characterized by proximal lumbosacral plexopathy and painful flexion of the ipsilateral hip with positive psoas muscle stretch test. Malignant involvement of the psoas major muscle was confirmed radiologically in all cases. Pain was intractable in 3 patients until time of death. We have termed this presentation the malignant psoas syndrome (MPS) and retrospective review of 427 oncology patients with “high risk” solid cancer culled no additional cases during the same 4–year period. We believe MPS to be a hitherto unreported complication of systemic cancer in which malignant involvement of the psoas muscle, in addition to producing severe nociceptive pain, contributes to the process of lumbosacral deafferentation. The clinical presentation, diagnosis and strategies of management of MPS are discussed.     

Therapy insight: AIDS-related malignancies--the influence of antiviral therapy on pathogenesis and management

Patients with HIV infection are at an increased risk of a number of malignancies, including Kaposi's sarcoma (KS) and certain B-cell lymphomas. Most of these tumors are caused by oncogenic DNA viruses, including KS-associated herpesvirus and Epstein-Barr virus. HIV contributes to the development of these tumors through several mechanisms, including immunodeficiency, immunodysregulation, and the effects of HIV proteins such as Tat. The development of highly active antiretroviral therapy (HAART) has reduced the incidence of many HIV-associated tumors and has generally improved their responsiveness to therapy. However, the number of people living with AIDS is increasing, and it is possible that the number of AIDS-associated malignancies will rise and the pattern of tumors will change as more people live longer with HIV infection. The goal of KS therapy is long-term tumor control with minimal toxicity. HAART is an important component of this therapy, and some patients do not require other KS-specific therapies. By contrast, the goal of AIDS-related lymphoma therapy in most cases is the attainment of a complete response with curative intent, and the benefits of administering HAART during therapy must be weighed against possible disadvantages. The past decade has seen substantial improvements in the treatment of AIDS-related lymphoma, which is attributed partially to a shift in tumor type and more effective regimens. There is currently an interest in developing new therapies for HIV-associated malignancies, based on viral, vascular or other pathogenesis-based targets.