Tumors in von Hippel–Lindau Syndrome: From Head to Toe—Comprehensive State-of-the-Art Review

Von Hippel–Lindau syndrome (VHL) is an autosomal-dominant hereditary tumor disease that arises owing to germline mutations in the VHL gene, located on the short arm of chromosome 3. Patients with VHL may develop multiple benign and malignant tumors involving various organ systems, including retinal hemangioblastomas (HBs), central nervous system (CNS) HBs, endolymphatic sac tumors, pancreatic neuroendocrine tumors, pancreatic cystadenomas, pancreatic cysts, clear cell renal cell carcinomas, renal cysts, pheochromocytomas, paragangliomas, and epididymal and broad ligament cystadenomas. The VHL/hypoxia-inducible factor pathway is believed to play a key role in the pathogenesis of VHL-related tumors. The diagnosis of VHL can be made clinically when the characteristic clinical history and findings have manifested, such as the presence of two or more CNS HBs. Genetic testing for heterozygous germline VHL mutation may also be used to confirm the diagnosis of VHL. Imaging plays an important role in the diagnosis and surveillance of patients with VHL. Familiarity with the clinical and imaging manifestations of the various VHL-related tumors is important for early detection and guiding appropriate management. The purpose of this article is to discuss the molecular cytogenetics and clinical manifestations of VHL, review the characteristic multimodality imaging features of the various VHL-related tumors affecting multiple organ systems, and discuss the latest advances in management of VHL, including current recommendations for surveillance and screening

Music and Music Therapy Is a Medicine for Stress

Stress is a feeling of emotional or physical tension. It can be triggered by any event or thought that causes you to feel dissatisfied, angry, or anxious. The body’s response to a challenge or demand is known as stress. The importance of developing cost-effective stress reduction interventions is high due to the difficulty of reducing or preventing stress without professional help and the large demand for non-pharmacological stress reduction interventions. Music therapy is the clinical application of musical therapies to improve a client’s quality of life based on scientific evidence. Music therapists use both active and receptive music experiences to help clients improve their health in cognitive, motor, emotional, communicative, social, sensory, and educational domains by using music and its many facets, which include physical, emotional, mental, social, aesthetic, and spiritual domains. Nowadays, stress is increasingly widespread among all individuals all over the world, and people are more aware of it than ever before. This chapter may assist the general public in gaining a broad understanding of the role of music therapy in stress management, as well as assisting individuals in self-recovery

Primary mucinous adenocarcinoma in a defunctionalized urinary bladder: a case report

<p>Abstract</p> <p>Introduction</p> <p>Malignancies are rare in defunctionalized bladders and are thought to arise from metaplasia secondary to chronic inflammation. Transitional cell and squamous cell carcinomas are the most common but there are three reported cases of mucinous adenocarcinoma.</p> <p>Case presentation</p> <p>We report a 57-year-old Caucasian man presenting with penile discharge for 30 years following ileal conduit surgery for neurogenic bladder, and who was found to have primary mucinous adenocarcinoma of his defunctionalized bladder.</p> <p>Conclusion</p> <p>Although urinary diversion without cystectomy is less common in current urologic practice, there are many patients with longstanding defunctionalized bladders. While there are no established surveillance protocols, defunctionalized bladder patients with urethral discharge should be evaluated.</p

Aberrant Promoter Methylation of Sparc in Ovarian Cancer1,2

Epigenetic silencing of tumor suppressor genes is a new focus of investigation in the generation and proliferation of carcinomas. Secreted protein acidic and rich in cysteine (SPARC) is reportedly detrimental to the growth of ovarian cancer cells and has been shown to be epigenetically silenced in several cancers. We hypothesized that SPARC is downregulated in ovarian cancer through aberrant promoter hypermethylation. To that end, we analyzed SPARC expression in ovarian cancer cell lines and investigated the methylation status of the Sparc promoter using methylation-specific polymerase chain reaction. Our results show that SPARC mRNA expression is decreased in three (33%) and absent in four (44%) of the nine ovarian cancer cell lines studied, which correlated with hypermethylation of the Sparc promoter. Treatment with the demethylating agent 5-aza-2′-deoxycytidine rescued SPARC mRNA and protein expression. Addition of exogenous SPARC, as well as ectopic expression by an adenoviral vector, resulted in decreased proliferation of ovarian cancer cell lines. Investigation of primary tumors revealed that the Sparc promoter is methylated in 68% of primary ovarian tumors and that the levels of SPARC protein decrease as the disease progresses from low to high grade. Lastly, de novo methylation of Sparc promoter was shown to be mediated by DNA methyltransferase 3a. These results implicate Sparc promoter methylation as an important factor in the genesis and survival of ovarian carcinomas and provide new insights into the potential use of SPARC as a novel biomarker and/or treatment modality for this disease

MCL-1 expression in B-cell non-Hodgkin’s lymphomas

B-cell non-Hodgkin’s lymphomas are known to express BCL-2 family proteins, of which the myeloid cell leukemia-1 (MCL-1) protein is a member. MCL-1 is involved in viability and immortalization of normal and neoplastic B cells, and expression is regulated transcriptionally and posttranscriptionally, resulting in an anti-apoptotic (full length) or a pro-apoptotic (short isoform) gene product. In this study, we assessed 151 B-cell lymphomas for MCL-1 expression and analyzed for expression of the full-length and short isoforms of MCL-1 in B-cell lymphoma cell lines. By using immunohistochemistry, a subset of neoplasms in 9 lymphoma types studied expressed MCL-1, but expression was more frequent and intense in high-grade (43 of 49, 88%) compared with low-grade (34 of 92, 37%) lymphomas ( P < 0.0001). In follicular lymphomas, MCL-1 expression positively correlated with increasing grade; 1 (14%) of eight grade 1, 7 (70%) of ten grade 2, and all 9 (100%) grade 3 were positive ( P < 0.0008). All plasma cell myeloma cases assessed were also MCL-1 positive. By using Western blot analysis, 6 of 7 high-grade B-cell lymphoma cell lines showed predominant expression of full-length MCL-1, compared with no or weak expression of the short isoform. One myeloma and 1 of 2 mantle cell lymphoma cell lines also tested showed only full-length isoform expression. Our data suggest that MCL-1 is frequently expressed in high-grade B-cell lymphomas and plasma cell myeloma, most likely in its full-length isoform that is an active anti-apoptotic gene product. MCL-1 expression also correlates with grade and may contribute to transformation in follicular lymphomas

ConCerv: a prospective trial of conservative surgery for low-risk early-stage cervical cancer

ObjectiveThe objective of the ConCerv Trial was to prospectively evaluate the feasibility of conservative surgery in women with early-stage, low-risk cervical cancer.MethodsFrom April 2010 to March 2019, a prospective, single-arm, multicenter study evaluated conservative surgery in participants from 16 sites in nine countries. Eligibility criteria included: (1) FIGO 2009 stage IA2–IB1 cervical carcinoma; (2) squamous cell (any grade) or adenocarcinoma (grade 1 or 2 only) histology; (3) tumor size <2 cm; (4) no lymphovascular space invasion; (5) depth of invasion <10 mm; (6) negative imaging for metastatic disease; and (7) negative conization margins. Cervical conization was performed to determine eligibility, with one repeat cone permitted. Eligible women desiring fertility preservation underwent a second surgery with pelvic lymph node assessment, consisting of sentinel lymph node biopsy and/or full pelvic lymph node dissection. Those not desiring fertility preservation underwent simple hysterectomy with lymph node assessment. Women who had undergone an 'inadvertent' simple hysterectomy with an unexpected post-operative diagnosis of cancer were also eligible if they met the above inclusion criteria and underwent a second surgery with pelvic lymph node dissection only.Results100 evaluable patients were enrolled. Median age at surgery was 38 years (range 23–67). Stage was IA2 (33%) and IB1 (67%). Surgery included conization followed by lymph node assessment in 44 women, conization followed by simple hysterectomy with lymph node assessment in 40 women, and inadvertent simple hysterectomy followed by lymph node dissection in 16 women. Positive lymph nodes were noted in 5 patients (5%). Residual disease in the post-conization hysterectomy specimen was noted in 1/40 patients—that is, an immediate failure rate of 2.5%. Median follow-up was 36.3 months (range 0.0–68.3). Three patients developed recurrent disease within 2 years of surgery—that is, a cumulative incidence of 3.5% (95% CI 0.9% to 9.0%).DiscussionOur prospective data show that select patients with early-stage, low-risk cervical carcinoma may be offered conservative surgery