Metastatic pheochromocytoma and paraganglioma: focus on therapeutics.

Metastatic pheochromocytomas and paragangliomas are rare and challenging tumors. The tumor burden, combined with excessive catecholamine production, predispose to a broad spectrum of complications that range from spinal cord compression to any organ damage, all of which may lead to decreased quality of life and overall survival. Current therapies include surgery, systemic chemotherapy and radiopharmaceutical agents. Surgery is often a preferred therapy because it may cure or allow a long-term remission in patients with locoregional or isolated resectable distant metastases. Additionally, surgery can palliate symptoms related to tumor burden or catecholamine excess. However, in patients for whom surgery is not an option, systemic chemotherapy and radiopharmaceutical agents are preferred options. Systemic chemotherapy and radiopharmaceutical agents such as 131I-Metaiodobenzylguanidine (131I-MIBG) may cause partial responses or stabilization of disease with better blood pressure control and symptomatic and performance status improvement. However, as these therapies are only palliative, patients' quality of life and personal preferences should always be considered. The recognition of molecular pathways involved in the pheochromocytoma and paraganglioma tumorigenesis has driven the development of new therapeutic options. Agents such as tyrosine kinase, MAPK, PI3K, or hypoxia inducible factor inhibitors, alone or in combination, may represent novel therapeutic strategies that could be evaluated in prospective clinical trials. Transcriptional profiling and the development of personalized cancer medicine will help to pave the way for more specific therapeutic approaches and combinations.

Inhibition of growth hormone receptor activation by pegvisomant may increase bone density in acromegaly.

Treatment of acromegaly with pegvisomant lowers serum IGF-1 and raises serum growth hormone. As both IGF-1 and GH are important for bone growth and remodeling, we were concerned that lowering of IGF-1 could cause loss of bone. To evaluate the effects of treatment of acromegaly with pegvisomant on bone mineral density (BMD) we developed an observational, prospective study. 7 acromegaly patients participated in the study. Male and female subjects aged 18 years or more were eligible to participate. Patients were eugonadal or on adequate gonadal replacement therapy for at least 3 years before participating in the study. These patients were treated with a mean dosage of 20 mg of pegvisomant daily for up to 7 years. Bone mineral density (BMD) was evaluated by dual X-ray absorbtiometry (DXA) at baseline, 8, and 18 months as a part of a prospective trial and periodically thereafter. Baseline mean serum insulin-like growth factor-1 (IGF-1) concentration±SD was elevated in all patients (679.86±138.21 ng/ml). The IGF-1 concentrations at 18 months decreased significantly from baseline (p=0.016). Wilcoxon signed-rank tests showed significant increases in the spine BMD from baseline to 18 months (p=0.016) and significant increases in the right hip BMD from baseline to 18 months (p=0.032). The range of the increases was 4.3-17.8% at 7 years. It is concluded that successful treatment of acromegaly with pegvisomant increases BMD.

A current review of the etiology, diagnosis, and treatment of pediatric pheochromocytoma and paraganglioma.

CONTEXT: Pheochromocytomas and paragangliomas (PHEO/PGL) are neuroendocrine tumors that arise from sympathetic and parasympathetic paraganglia. Diagnosed rarely during childhood, PHEO/PGL are nonetheless important clinical entities, particularly given our evolving understanding of their pathophysiology. EVIDENCE ACQUISITION: We identified articles through the U.S. National Library of Medicine by using the search terms pheochromocytoma and paraganglioma. Results were narrowed to manuscripts that included children and studies related to the genetics of PHEO/PGL. Web-based resources for genetic disorders were also used. For all articles, we performed subsequent reference searches and verification of source data. EVIDENCE SYNTHESIS: Up to 20% of PHEO/PGL are diagnosed in children. Most are functional tumors, and clinical presentation includes symptoms related to catecholamine hypersecretion and/or tumor mass effect. Increasingly, PHEO/PGL are identified during presymptomatic screening in children with genetic syndromes associated with PHEO/PGL (multiple endocrine neoplasia type 2, von Hippel-Lindau disease, and the paraganglioma syndromes). Plasma and/or urine metanephrines are the best diagnostic test for a functional tumor, and the management of pediatric patients is similar to adults. Genetic counseling should be undertaken in all cases. Although most pediatric PHEO/PGL are benign, these tumors can occasionally metastasize, a condition for which no curative treatment exists. CONCLUSIONS: Although PHEO/PGL are rarely diagnosed during childhood, the pediatric provider should be able to recognize and screen for such tumors, particularly in the context of a known genetic predisposition. Optimal care of these children includes a multidisciplinary team approach at centers experienced in the evaluation and treatment of these uncommon yet fascinating endocrine neoplasms.

[Quality of the presentation of free research papers in the National Congress of Gastroenterology: Morelia-1997]. / Calidad de presentación de los trabajos libres de investigación en el Congreso Nacional de Gastroenterología: Morelia-1997.

BACKGROUND: The quality of the presentation of a free paper in a medical congress is not necessarily related to the quality of the methodology. OBJECTIVE: To analyze the quality of the presentation of the free papers in the National Congress of Gastroenterology in Mexico (Morelia-1997). METHODS: A prospective study was designed to evaluate the following aspects: Limitation to time assigned, adequate use and design of slides, and mentioning of the main methodologic characteristics. RESULTS: There was a high quality of presentation in the majority of papers. The most frequent problems identified, amenable to improvement, were non-limitation to assigned time (24%), as well as problems in the design of slides (too many lines/columns in 32% and excessive number in 23%). CONCLUSIONS: The knowledge of the results may help to improve the presentations of the free papers in the national congresses of gastroenterology.

[Total proctocolectomy with ileo-anal reservoir in "J". Experience at the Salvador Zubirán National Institute of Nutrition]. / Proctocolectomía total con anastomosis ileo-anal de reservorio en "J". Experiencia en el Instituto Nacional de la Nutrición Salvador Zubirán.

BACKGROUND: Total proctocolectomy with ileal pouch-anal anastomosis (TPCIAA) is the procedure of choice for patients with Ulcerative Colitis and Familial Adenomatous Polyposis. The frequency of presentation of both diseases is low in Mexico, therefore the experience with the surgical procedure is limited. OBJECTIVE: To analyze the operative morbidity and mortality and long-term functional results in a series of patients operated upon with the TPCIAA in a referral center in Mexico. MATERIAL AND METHODS: Retrospective analysis of 44 consecutive patients operated upon from 1987 through 1997. The operation included resection of the anal transitional zone, handsewn anastomosis of a "J" pouch, and diverting ileostomy in all cases. Operative morbidity and mortality, and long-term functional results and complications were determined. RESULTS: Mean age was 33 +/- 15 years. There were 52% women and 48% men. Diagnoses were ulcerative colitis in 59% and familial polyposis in 36%. Global morbidity was 39%, and mortality 2%. With a mean follow-up of 24 months, mean number of bowel movements was 4, 10% of patients had diurnal spotting, 30% nocturnal spotting, and no patient had gross incontinence. Three patients presented pouchitis with adequate response to antibiotics. Two patients presented long-term pouch fistulas that did not require pouch excision. CONCLUSIONS: The TPCIAA is a feasible operation with acceptable rates of morbidity and mortality and satisfactory functional results.