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The Oncologist Sep 2017Appendiceal mucinous neoplasms (AMNs) are a rare and heterogeneous disease for which clinical management is challenging. We aim to review the literature regarding... (Review)
Review
OBJECTIVE
Appendiceal mucinous neoplasms (AMNs) are a rare and heterogeneous disease for which clinical management is challenging. We aim to review the literature regarding modalities of treatment to guide the management of AMNs.
METHODS AND REVIEW CRITERIA
We conducted a PubMed search in February 2016 for English-language publications, using the terms "appendiceal," "appendix," "carcinoma," "cancer," "mucinous," "treatment," "genes," "target," "genomic," and terms listed in the articles' subheadings. Published reports and abstracts from the American Society of Clinical Oncology meetings were also searched.
RESULTS
In this review, we summarize current data and controversies in AMN classification, clinical presentation, molecular alterations, treatment outcomes with regard to cytoreductive surgery, hyperthermic intraperitoneal chemotherapy (HIPEC), and the role of systemic chemotherapy.
CONCLUSION
Appendiceal mucinous neoplasms are a heterogeneous group of tumors with a rising incidence. Treatment is based on stage and histology. Low-grade tumors are treated surgically with resection of the primary site in early stage disease, or peritoneal debulking and HIPEC in patients with advanced stage disease. Treatment of high-grade tumors requires further prospective trials, and options include debulking surgery and HIPEC with or without preoperative chemotherapy. Trials evaluating novel therapies based on the molecular profiling of AMN tumors are needed to evaluate therapeutic options in patients who are not surgical candidates.
IMPLICATIONS FOR PRACTICE
This review provides a reference to guide gastroenterologists, pathologists, surgeons, and oncologists in the management of appendiceal mucinous neoplasms (AMNs), a rare and heterogeneous disease with no consensus on histologic classification or guidelines for treatment algorithms. This review summarizes all AMN classifications and proposes a treatment algorithm based on stage and histology of disease.
Topics: Adenocarcinoma, Mucinous; Antineoplastic Combined Chemotherapy Protocols; Appendiceal Neoplasms; Appendix; Cytoreduction Surgical Procedures; Humans; Hyperthermia, Induced; Neoplasm Staging; Practice Guidelines as Topic; Rare Diseases; Treatment Outcome
PubMed: 28663356
DOI: 10.1634/theoncologist.2017-0081 -
CA: a Cancer Journal For Clinicians Jul 2019Ovarian cancer is the second most common cause of gynecologic cancer death in women around the world. The outcomes are complicated, because the disease is often... (Review)
Review
Ovarian cancer is the second most common cause of gynecologic cancer death in women around the world. The outcomes are complicated, because the disease is often diagnosed late and composed of several subtypes with distinct biological and molecular properties (even within the same histological subtype), and there is inconsistency in availability of and access to treatment. Upfront treatment largely relies on debulking surgery to no residual disease and platinum-based chemotherapy, with the addition of antiangiogenic agents in patients who have suboptimally debulked and stage IV disease. Major improvement in maintenance therapy has been seen by incorporating inhibitors against poly (ADP-ribose) polymerase (PARP) molecules involved in the DNA damage-repair process, which have been approved in a recurrent setting and recently in a first-line setting among women with BRCA1/BRCA2 mutations. In recognizing the challenges facing the treatment of ovarian cancer, current investigations are enlaced with deep molecular and cellular profiling. To improve survival in this aggressive disease, access to appropriate evidence-based care is requisite. In concert, realizing individualized precision medicine will require prioritizing clinical trials of innovative treatments and refining predictive biomarkers that will enable selection of patients who would benefit from chemotherapy, targeted agents, or immunotherapy. Together, a coordinated and structured approach will accelerate significant clinical and academic advancements in ovarian cancer and meaningfully change the paradigm of care.
Topics: Antineoplastic Agents; Carcinoma, Ovarian Epithelial; Cytoreduction Surgical Procedures; Female; Humans; Molecular Targeted Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Ovarian Neoplasms; Precision Medicine; Second-Look Surgery
PubMed: 31099893
DOI: 10.3322/caac.21559 -
World Journal of Gastroenterology May 2020Pancreatic neuroendocrine tumors (pNETs) are a heterogeneous group of tumors with complicated treatment options that depend on pathological grading, clinical staging,... (Review)
Review
Pancreatic neuroendocrine tumors (pNETs) are a heterogeneous group of tumors with complicated treatment options that depend on pathological grading, clinical staging, and presence of symptoms related to hormonal secretion. With regard to diagnosis, remarkable advances have been made: Chromogranin A is recommended as a general marker for pNETs. But other new biomarker modalities, like circulating tumor cells, multiple transcript analysis, microRNA profile, and cytokines, should be clarified in future investigations before clinical application. Therefore, the currently available serum biomarkers are insufficient for diagnosis, but reasonably acceptable in evaluating the prognosis of and response to treatments during follow-up of pNETs. Surgical resection is still the only curative therapeutic option for localized pNETs. However, a debulking operation has also been proven to be effective for controlling the disease. As for drug therapy, steroids and somatostatin analogues are the first-line therapy for those with positive expression of somatostatin receptor, while everolimus and sunitinib represent important progress for the treatment of patients with advanced pNETs. Great progress has been achieved in the combination of systematic therapy with local control treatments. The optimal timing of local control intervention, planning of sequential therapies, and implementation of multidisciplinary care remain pending.
Topics: Ablation Techniques; Antineoplastic Agents; Biomarkers, Tumor; Chemotherapy, Adjuvant; Combined Modality Therapy; Cytoreduction Surgical Procedures; Disease-Free Survival; Humans; Lymph Node Excision; Molecular Targeted Therapy; Neoplasm Grading; Neoplasm Staging; Neuroendocrine Tumors; Pancreas; Pancreatectomy; Pancreatic Neoplasms; Patient Care Team; Prognosis; Progression-Free Survival; Somatostatin; Treatment Outcome
PubMed: 32476795
DOI: 10.3748/wjg.v26.i19.2305 -
International Journal of Molecular... Feb 2019Among a litany of malignancies affecting the female reproductive tract, that of the ovary is the most frequently fatal. Moreover, while the steady pace of scientific... (Review)
Review
Among a litany of malignancies affecting the female reproductive tract, that of the ovary is the most frequently fatal. Moreover, while the steady pace of scientific discovery has fuelled recent ameliorations in the outcomes of many other cancers, the rates of mortality for ovarian cancer have been stagnant since around 1980. Yet despite the grim outlook, progress is being made towards better understanding the fundamental biology of this disease and how its biology in turn influences clinical behaviour. It has long been evident that ovarian cancer is not a unitary disease but rather a multiplicity of distinct malignancies that share a common anatomical site upon presentation. Of these, the high-grade serous subtype predominates in the clinical setting and is responsible for a disproportionate share of the fatalities from all forms of ovarian cancer. This review aims to provide a detailed overview of the clinical-pathological features of ovarian cancer with a particular focus on the high-grade serous subtype. Along with a description of the relevant clinical aspects of this disease, including novel trends in treatment strategies, this text will inform the reader of recent updates to the scientific literature regarding the origin, aetiology and molecular-genetic basis of high-grade serous ovarian cancer (HGSOC).
Topics: Animals; Biomarkers, Tumor; Cystadenocarcinoma, Serous; Drug Resistance, Neoplasm; Female; Humans; Neoplasm Grading; Ovarian Neoplasms; Risk Factors
PubMed: 30813239
DOI: 10.3390/ijms20040952 -
The New England Journal of Medicine Jan 2003Although tumor-infiltrating T cells have been documented in ovarian carcinoma, a clear association with clinical outcome has not been established.
BACKGROUND
Although tumor-infiltrating T cells have been documented in ovarian carcinoma, a clear association with clinical outcome has not been established.
METHODS
We performed immunohistochemical analysis of 186 frozen specimens from advanced-stage ovarian carcinomas to assess the distribution of tumor-infiltrating T cells and conducted outcome analyses. Molecular analyses were performed in some tumors by real-time polymerase chain reaction.
RESULTS
CD3+ tumor-infiltrating T cells were detected within tumor-cell islets (intratumoral T cells) in 102 of the 186 tumors (54.8 percent); they were undetectable in 72 tumors (38.7 percent); the remaining 12 tumors (6.5 percent) could not be evaluated. There were significant differences in the distributions of progression-free survival and overall survival according to the presence or absence of intratumoral T cells (P<0.001 for both comparisons). The five-year overall survival rate was 38.0 percent among patients whose tumors contained T cells and 4.5 percent among patients whose tumors contained no T cells in islets. Significant differences in the distributions of progression-free survival and overall survival according to the presence or absence of intratumoral T cells (P<0.001 for both comparisons) were also seen among 74 patients with a complete clinical response after debulking and platinum-based chemotherapy: the five-year overall survival rate was 73.9 percent among patients whose tumors contained T cells and 11.9 percent among patients whose tumors contained no T cells in islets. The presence of intratumoral T cells independently correlated with delayed recurrence or delayed death in multivariate analysis and was associated with increased expression of interferon-gamma, interleukin-2, and lymphocyte-attracting chemokines within the tumor. The absence of intratumoral T cells was associated with increased levels of vascular endothelial growth factor.
CONCLUSIONS
The presence of intratumoral T cells correlates with improved clinical outcome in advanced ovarian carcinoma.
Topics: Adult; Aged; Aged, 80 and over; Disease Progression; Female; Flow Cytometry; Humans; Immunohistochemistry; Lymphocytes, Tumor-Infiltrating; Middle Aged; Multivariate Analysis; Neoplasm Recurrence, Local; Ovarian Neoplasms; Polymerase Chain Reaction; Survival Analysis; T-Lymphocytes
PubMed: 12529460
DOI: 10.1056/NEJMoa020177 -
The Journal of Laryngology and Otology May 2016This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. This paper provides...
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. This paper provides recommendations on the management of thyroid cancer in adults and is based on the 2014 British Thyroid Association guidelines. Recommendations • Ultrasound scanning (USS) of the nodule or goitre is a crucial investigation in guiding the need for fine needle aspiration cytology (FNAC). (R) • FNAC should be considered for all nodules with suspicious ultrasound features (U3-U5). If a nodule is smaller than 10 mm in diameter, USS guided FNAC is not recommended unless clinically suspicious lymph nodes on USS are also present. (R) • Cytological analysis and categorisation should be reported according to the current British Thyroid Association Guidance. (R) • Ultrasound scanning assessment of cervical nodes should be done in FNAC-proven cancer. (R) • Magnetic resonance imaging (MRI) or computed tomography (CT) should be done in suspected cases of retrosternal extension, fixed tumours (local invasion with or without vocal cord paralysis) or when haemoptysis is reported. When CT with contrast is used pre-operatively, there should be a two-month delay between the use of iodinated contrast media and subsequent radioactive iodine (I131) therapy. (R) • Fluoro-deoxy-glucose positron emission tomography imaging is not recommended for routine evaluation. (G) • In patients with thyroid cancer, assessment of extrathyroidal extension and lymph node disease in the central and lateral neck compartments should be undertaken pre-operatively by USS and cross-sectional imaging (CT or MRI) if indicated. (R) • For patients with Thy 3f or Thy 4 FNAC a diagnostic hemithyroidectomy is recommended. (R) • Total thyroidectomy is recommended for patients with tumours greater than 4 cm in diameter or tumours of any size in association with any of the following characteristics: multifocal disease, bilateral disease, extrathyroidal spread (pT3 and pT4a), familial disease and those with clinically or radiologically involved nodes and/or distant metastases. (R) • Subtotal thyroidectomy should not be used in the management of thyroid cancer. (G) • Central compartment neck dissection is not routinely recommended for patients with papillary thyroid cancer without clinical or radiological evidence of lymph node involvement, provided they meet all of the following criteria: classical type papillary thyroid cancer, patient less than 45 years old, unifocal tumour, less than 4 cm, no extrathyroidal extension on ultrasound. (R) • Patients with metastases in the lateral compartment should undergo therapeutic lateral and central compartment neck dissection. (R) • Patients with follicular cancer with greater than 4 cm tumours should be treated with total thyroidectomy. (R) • I131 ablation should be carried out only in centres with appropriate facilities. (R) • Serum thyroglobulin (Tg) should be checked in all post-operative patients with differentiated thyroid cancer (DTC), but not sooner than six weeks after surgery. (R) • Patients who have undergone total or near total thyroidectomy should be started on levothyroxine 2 µg per kg or liothyronine 20 mcg tds after surgery. (R) • The majority of patients with a tumour more than 1 cm in diameter, who have undergone total or near-total thyroidectomy, should have I131 ablation. (R) • A post-ablation scan should be performed 3-10 days after I131 ablation. (R) • Post-therapy dynamic risk stratification at 9-12 months is used to guide further management. (G) • Potentially resectable recurrent or persistent disease should be managed with surgery whenever possible. (R) • Distant metastases and sites not amenable to surgery which are iodine avid should be treated with I131 therapy. (R) • Long-term follow-up for patients with differentiated thyroid cancer (DTC) is recommended. (G) • Follow-up should be based on clinical examination, serum Tg and thyroid-stimulating hormone assessments. (R) • Patients with suspected medullary thyroid cancer (MTC) should be investigated with calcitonin and carcino-embryonic antigen levels (CEA), 24 hour catecholamine and nor metanephrine urine estimation (or plasma free nor metanephrine estimation), serum calcium and parathyroid hormone. (R) • Relevant imaging studies are advisable to guide the extent of surgery. (R) • RET (Proto-oncogene tyrosine-protein kinase receptor) proto-oncogene analysis should be performed after surgery. (R) • All patients with known or suspected MTC should have serum calcitonin and biochemical screening for phaeochromocytoma pre-operatively. (R) • All patients with proven MTC greater than 5 mm should undergo total thyroidectomy and central compartment neck dissection. (R) • Patients with MTC with lateral nodal involvement should undergo selective neck dissection (IIa-Vb). (R) • Patients with MTC with central node metastases should undergo ipsilateral prophylactic lateral node dissection. (R) • Prophylactic thyroidectomy should be offered to RET-positive family members. (R) • All patients with proven MTC should have genetic screening. (R) • Radiotherapy may be useful in controlling local symptoms in patients with inoperable disease. (R) • Chemotherapy with tyrosine kinase inhibitors may help in controlling local symptoms. (R) • For individuals with anaplastic thyroid carcinoma, initial assessment should focus on identifying the small proportion of patients with localised disease and good performance status, which may benefit from surgical resection and other adjuvant therapies. (G) • The surgical intent should be gross tumour resection and not merely an attempt at debulking. (G).
Topics: Biopsy, Needle; Carcinoma, Neuroendocrine; Humans; Interdisciplinary Communication; Lymphatic Metastasis; Magnetic Resonance Imaging; Neoplasm Recurrence, Local; Neoplasm Staging; Postoperative Care; Proto-Oncogene Mas; Thyroid Gland; Thyroid Neoplasms; Thyroidectomy; Tomography, X-Ray Computed; United Kingdom
PubMed: 27841128
DOI: 10.1017/S0022215116000578 -
Cell Reports May 2023Glioblastoma (GBM) recurrence originates from invasive margin cells that escape surgical debulking, but to what extent these cells resemble their bulk counterparts...
Glioblastoma (GBM) recurrence originates from invasive margin cells that escape surgical debulking, but to what extent these cells resemble their bulk counterparts remains unclear. Here, we generated three immunocompetent somatic GBM mouse models, driven by subtype-associated mutations, to compare matched bulk and margin cells. We find that, regardless of mutations, tumors converge on common sets of neural-like cellular states. However, bulk and margin have distinct biology. Injury-like programs associated with immune infiltration dominate in the bulk, leading to the generation of lowly proliferative injured neural progenitor-like cells (iNPCs). iNPCs account for a significant proportion of dormant GBM cells and are induced by interferon signaling within T cell niches. In contrast, developmental-like trajectories are favored within the immune-cold margin microenvironment resulting in differentiation toward invasive astrocyte-like cells. These findings suggest that the regional tumor microenvironment dominantly controls GBM cell fate and biological vulnerabilities identified in the bulk may not extend to the margin residuum.
Topics: Animals; Mice; Glioblastoma; Cell Differentiation; Tumor Microenvironment; Neural Stem Cells; Brain Neoplasms
PubMed: 37149862
DOI: 10.1016/j.celrep.2023.112472 -
Neurologia Medico-chirurgica Jan 2018Optic pathway/hypothalamic gliomas (OP/HGs) are rare astrocytic tumors that appear more commonly among young children and often are unresectable. They comprise... (Review)
Review
Optic pathway/hypothalamic gliomas (OP/HGs) are rare astrocytic tumors that appear more commonly among young children and often are unresectable. They comprise approximately 2% of all central nervous system tumors and account for 3-5% of pediatric intracranial tumors. Initial manifestations are often visual disturbances, endocrinopathies and hypothalamic dysfunction such as the diencephalic syndrome, and sometimes hydrocephalus due to cerebrospinal fluid (CSF) outflow obstruction. In many cases, the tumors are diagnosed late in the clinical course because they silently enlarge. These tumors consist mostly of histologically benign, World Health Organization (WHO) grade I tumors represented by pilocytic astrocytomas (PA), the rest being pilomyxoid astrocytomas (PXA) - WHO grade II tumors. In young pediatric patients, however, can be seen PXA that show aggressive clinical course such as CSF dissemination. Our small series of 14 non-Neurofibromatosis type 1 (NF-1) OP/HGs PA patients underwent extended resection without any adjuvant treatments. The median age at initial treatment was 11.5 ± 6.90 years (range, 1-25 years) and median follow up 85.5 ± 25.0 months. Surgical resection for OP/HGs results in acceptable middle-term survival, tumor control and functional outcome equivalent to chemotherapy. There is, however, no longer doubt that chemotherapy with or without biopsy and as-needed debulking surgery remains the golden standard in management of OP/H. Clinical conditions and treatment plans for OP/HGs vary depending on their structure of origin.
Topics: Adolescent; Brain Neoplasms; Child; Child, Preschool; Female; Glioma; Humans; Hypothalamus; Infant; Male; Optic Chiasm; Optic Tract; Young Adult
PubMed: 29118304
DOI: 10.2176/nmc.ra.2017-0081 -
Neurology India 2021The prevalence of hydrocephalus among patients with neurofibromatosis type I (NF1) is estimated to be between 1 and 13%. Aqueductal webs, chiasmatic-hypothalamic tumors,... (Review)
Review
The prevalence of hydrocephalus among patients with neurofibromatosis type I (NF1) is estimated to be between 1 and 13%. Aqueductal webs, chiasmatic-hypothalamic tumors, and thalamic mass effect related to NF changes are the common causes of NF1-related hydrocephalus. Brain tumors and moyamoya syndrome may mimic the clinical presentation of hydrocephalus in children with NF1, and should be ruled out while evaluating children with headaches. Treatment of NF1-related hydrocephalus should be personally tailored, including shunts, endoscopic procedures such as septostomy and third ventriculostomy, and tumor resection or debulking. Despite these personalized treatments, many of the primary treatments (including shunts and endoscopic procedures) fail, and patients should be screened and followed accordingly. In the current manuscript, we review the causes of NF1-related hydrocephalus, as well as treatment options.
Topics: Brain Neoplasms; Cerebral Aqueduct; Child; Humans; Hydrocephalus; Neurofibromatosis 1; Ventriculostomy
PubMed: 35102991
DOI: 10.4103/0028-3886.332254 -
Seminars in Oncology Dec 2010Parathyroid cancer is an uncommon malignancy and rare cause of primary hyperparathyroidism (HPT) with a high morbidity and patient death in advanced cases usually... (Review)
Review
Parathyroid cancer is an uncommon malignancy and rare cause of primary hyperparathyroidism (HPT) with a high morbidity and patient death in advanced cases usually resulting from intractable hypercalcemia. Inactivation of the HRPT2/CDC73 gene, encoding the putative tumor-suppressor protein parafibromin and discovered in the context of the hyperparathyroidism-jaw tumor (HPT-JT) syndrome, is a common, somatic event in most parathyroid cancers. Approximately 25% of patients with apparently sporadic parathyroid cancer carry germline HRPT2/CDC73 mutation. Germline DNA analysis for HRPT2/CDC73 mutation is recommended in all patients with parathyroid cancer because of the potential benefit for first-degree relatives, who should nevertheless undergo serum calcium screening. The histopathologic diagnosis of parathyroid cancer is nonspecific unless vascular, lymphatic, capsular, or soft tissue invasion is seen, or metastases are clinically evident. Immunohistochemical analysis of parathyroid tumors for loss of parafibromin expression offers promise as a diagnostic tool. En bloc tumor resection offers the highest chance of cure in patients with suspected parathyroid carcinoma. No adjuvant chemotherapy regimen has yet proven effective, and the role of local adjuvant radiotherapy is being evaluated. Metastatic disease can be palliated with surgical debulking. Medical therapy with the calcimimetic cinacalcet and bisphosphonates can ameliorate hypercalcemia in patients with inoperable disease.
Topics: Biomarkers, Tumor; Disease Progression; Humans; Hypercalcemia; Mutation; Parathyroid Neoplasms; Parathyroidectomy; Prognosis; Tumor Suppressor Proteins
PubMed: 21167377
DOI: 10.1053/j.seminoncol.2010.10.013