Understanding the perspective of women who use the Billings Ovulation Method®: a focus group study.

BACKGROUND: The Billings Ovulation Method®(the Billings Method) is a fertility awareness-based method (FABM) of family planning that relies on the observation of patterns of fertility and infertility based on vulvar sensations and appearance of discharges. This allows people to choose when to have intercourse, depending on whether they want to avoid or achieve pregnancy. Few studies have documented user experiences with FABMs. METHODS: We conducted four virtual focus groups (FGs) in May and June 2021 with current adult women users of the Billings Method. We asked questions about users' reasons for selecting a FABM and the Billings Method, positive experiences and challenges learning and using the Billings Method, and suggestions for improving the user experience. We performed a content analysis of the transcribed FGs to explore key themes from the discussions. COREQ guidelines were followed. RESULTS: Twenty women between the ages of 23 and 43 participated in the FGs. Reasons women described choosing a FABM included to follow religious beliefs, to avoid side effects of hormonal contraception, and/or to learn more about their bodies. Reasons for selecting the Billings Method included perceiving it as more precise and easier to understand than other FABMs, having a scientific basis, and being recommended by family and friends. Experiences related to learning and using the Billings Method were mainly positive. They included finding the method easy to use and learn, successfully using it to either postpone or achieve a pregnancy and increasing their awareness of their bodies. Challenges for participants included the inherent learning curve for identifying sensations at the vulva and the required periods of abstinence. Participants provided suggestions and recommendations for improving users' experience, including raising awareness of the Billings Method among healthcare providers. CONCLUSIONS: Users of the Billings Method expressed an overall positive experience when learning and using it for family planning and body awareness. Some challenges were identified that offer opportunities to improve how the Billings Method is taught and delivered. These findings can also enhance healthcare providers' interactions with FABM users, including those of the Billings Method.

Association of distance to swine concentrated animal feeding operations with immune-mediated diseases: An exploratory gene-environment study.

BACKGROUND: Concentrated animal feeding operations (CAFOs) are a source of environmental pollution and have been associated with a variety of health outcomes. Immune-mediated diseases (IMD) are characterized by dysregulation of the normal immune response and, while they may be affected by gene and environmental factors, their association with living in proximity to a CAFO is unknown. OBJECTIVES: We explored gene, environment, and gene-environment (GxE) relationships between IMD, CAFOs, and single nucleotide polymorphisms (SNPs) of prototypical xenobiotic response genes AHR, ARNT, and AHRR and prototypical immune response gene PTPN22. METHODS: The exposure analysis cohort consisted of 6,464 participants who completed the Personalized Environment and Genes Study Health and Exposure Survey and a subset of 1,541 participants who were genotyped. We assessed the association between participants' residential proximity to a CAFO in gene, environment, and GxE models. We recombined individual associations in a transethnic model using METAL meta-analysis. RESULTS: In White participants, ARNT SNP rs11204735 was associated with autoimmune diseases and rheumatoid arthritis (RA), and ARNT SNP rs1889740 was associated with RA. In a transethnic genetic analysis, ARNT SNPs rs11204735 and rs1889740 and PTPN22 SNP rs2476601 were associated with autoimmune diseases and RA. In participants living closer than one mile to a CAFO, the log-distance to a CAFO was associated with autoimmune diseases and RA. In a GxE interaction model, White participants with ARNT SNPs rs11204735 and rs1889740 living closer than eight miles to a CAFO had increased odds of RA and autoimmune diseases, respectively. The transethnic model revealed similar GxE interactions. CONCLUSIONS: Our results suggest increased risk of autoimmune diseases and RA in those living in proximity to a CAFO and a potential role of the AHR-ARNT pathway in conferring risk. We also report the first association of ARNT SNPs rs11204735 and rs1889740 with RA. Our findings, if confirmed, could allow for novel genetically-targeted or other preventive approaches for certain IMD.

Impact of Surgical Resection of the Primary Tumor on Overall Survival in Patients With Metastatic Pheochromocytoma or Sympathetic Paraganglioma.

OBJECTIVE: To determine whether primary tumor resection in patients with metastatic pheochromocytoma or paraganglioma (PPG) is associated with longer overall survival (OS). BACKGROUND: Patients with metastatic PPG have poor survival outcomes. The impact of surgical resection of the primary tumor on OS is not known. METHODS: We retrospectively studied patients with metastatic PPG treated at the University of Texas, MD Anderson Cancer Center from January 2000 through January 2015. Kaplan-Meier analysis with log-rank tests was used to compare OS among patients undergoing primary tumor resection and patients not treated surgically. Propensity score method was applied to adjust for selection bias using demographic, clinical, biochemical, genetic, imaging, and pathologic information. RESULTS: A total of 113 patients with metastatic PPG were identified. Eighty-nine (79%) patients had surgery and 24 (21%) patients did not. Median OS was longer in patients who had surgery than in patients who did not [148 months, 95% confidence interval (CI) 112.8-183.2 months vs 36 months, 95% CI 27.2-44.8 months; P < 0.001].Fifty-three (46%) patients had synchronous metastases; of these patients, those who had surgery had longer OS than those who did not (85 months, 95% CI 64.5-105.4 months vs 36 months, 95% CI 29.7-42.3 months; P < 0.001). Patients who had surgery had a similar ECOG performance status to the ones who did not (P = 0.1798, two sample t test; P = 0.2449, Wilcoxon rank sum test). Univariate and propensity score analysis confirmed that patients treated with surgery had longer OS than those not treated surgically irrespective of age, race, primary tumor size and location, number of metastatic sites, and genetic background (log-rank P < 0.001).In patients with hormonally active tumors (70.8%), the symptoms of catecholamine excess improved after surgery. However, the tumor burden was a more important determinant of OS than hormonal secretion. CONCLUSIONS: Primary tumor resection in patients with metastatic PPG appeared to be associated with improved OS. In patients with hormonally active tumors, surgical resection led to better blood pressure control.

Constipation: an overlooked, unmanaged symptom of patients with pheochromocytoma and sympathetic paraganglioma.

OBJECTIVE: Pheochromocytomas (PHs) and sympathetic paragangliomas (PGs) are tumors that produce catecholamines, predisposing patients to cardiovascular disease and gastrointestinal effects such as constipation. OBJECTIVES: i) determine the prevalence of constipation, its risk factors, and its impact on survival; ii) identify whether a systematic combination of fiber, water, and laxatives was effective for treatment of constipation. DESIGN AND METHODS: We retrospectively studied 396 patients with PH/PG diagnosed in 2005-2014. The study population was patients with constipation as a presenting symptom; the control group was patients without constipation as a presenting symptom. The MD Anderson Symptom Inventory was used to assess constipation and quality of life. RESULTS: Twenty-three patients (6%) had constipation. Constipation was associated with headaches, palpitations, diaphoresis, weight loss, and excessive noradrenaline production (P<0.0001). Eighteen of these patients had non-metastatic primary tumors larger than 5 cm and/or extensive metastases. No statistically significant differences in age, sex, and genotype were noted between the study and control groups. In patients without metastases, resection of the primary tumor led to symptom disappearance. A systematic combination of fiber, water, and laxatives was associated with symptom improvement. Two patients who presented unmanaged constipation died because of sepsis from toxic megacolon. CONCLUSIONS: Constipation is a rare and potentially lethal complication in patients with PH/PGs. Severe constipation can be prevented by recognizing and treating mild symptoms.

Impact of surgical resection for subdiaphragmatic paragangliomas.

BACKGROUND: Subdiaphragmatic paraganglioma is a rare neuroendocrine tumor for which scarce data exist regarding long-term patient outcome following resection. The aim of this study was to determine the association of surgical resection with survival. METHODS: A retrospective study at a tertiary care center was performed. Demographics, genetics, histology, and operative details were reviewed. Patients were grouped according to margin status (R0, R1, or R2) and survival calculated. RESULTS: A total of 50 patients with subdiaphragmatic paragangliomas underwent primary resection from 1999 to 2012. Median age at operation was 46 years, with a median tumor size of 6.0 cm. Of these patients, 30 (60 %) had a R0 resection, 11 (22 %) had a R1 resection, and 9 (18 %) had a R2 resection. There was no operative mortality, and 17 (34 %) patients had metastatic disease. Six (12 %) patients died, four (8 %) of whom had metastatic disease. Univariate analysis identified that age >50 years (p = 0.02) and undergoing a R2 resection (p = 0.03) were associated with a shorter overall survival (OS). Those with metastases at some point after their initial diagnosis had a shorter disease-free survival (DFS) than those without metastases (p = 0.04). Of 27 patients tested, 12 (44 %) had a germline succinyl dehydrogenase B (SDHB) mutation. SDHB immunohistochemistry identified 18 patients (of 27 who underwent staining) who had loss of SDHB expression in which 7 of 11 patients (63 %) who underwent genetic testing had a genetic mutation. CONCLUSIONS: Surgical resection of subdiaphragmatic paraganglioma is safe. Survival was longest in patients who were younger, with no metastases, or had a R0 or R1 resection. Patients who test negative for a germline mutation should undergo SDHB immunostaining to identify potential hereditary carriers missed by current genetic testing.

Adrenocortical carcinoma: clinical outcomes and prognosis of 330 patients at a tertiary care center.

OBJECTIVE: Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis. Herein, we describe the clinical features and outcomes for a large series of ACC patients. DESIGN AND METHODS: Retrospective review of ACC patients seen at The University of Texas MD Anderson Cancer Center from 1998 through 2011. RESULTS: A total of 330 patients with median age at diagnosis of 48.5 years; 12 (3.6%) patients were under 18 years. Hormonally functioning tumors represented 41.8% (n=138) of all cases. Surgical resection for the primary tumor was done in 275 (83.3%) patients (45 at MD Anderson (16.4%)). For those who had surgical resection, the median local-recurrence-free time was 1.04 years. Factors associated with local recurrence included positive surgical margins (P=0.007) and advanced disease stage (P=0.026). Median overall survival time for all patients was 3.21 years. Median survival times were 24.1, 6.08, 3.47, and 0.89 years for stages I, II, III, and IV respectively. In multivariable analysis, older age, functioning tumors, and higher disease stage remained significant prognostic factors associated with poor survival. CONCLUSION: ACC prognosis remains poor with the use of currently available treatments. Older age, functioning tumors, and incomplete resections are clinical factors associated with poor survival. Surgical expertise is important to achieve complete resections and to improve outcome.

The characterization of pheochromocytoma and its impact on overall survival in multiple endocrine neoplasia type 2.

CONTEXT: Pheochromocytoma (PHEO) occurs in 50% of patients with multiple endocrine neoplasia type 2 (MEN2). It is unknown if the presence of PHEO is associated with more aggressive medullary thyroid cancer (MTC). OBJECTIVE: To present our experience with MEN2 PHEO and evaluate whether PHEO impacts MTC overall survival in patients with RET codon 634 mutations. DESIGN: We performed a retrospective chart review of MEN2 patients at MD Anderson Cancer Center from 1960 through 2012. PATIENTS: The study group comprised 85 patients (group 1) with MEN2-associated PHEO. Of these, 59 patients (subgroup 1) with RET codon 634 mutations were compared to 48 patients (group 2) with RET codon 634 mutations, but without MEN2-associated PHEO. MAIN OUTCOME MEASURES: Of 85 patients with MEN2 and PHEO, 70 had MEN2A and 15 had MEN2B. Median age at PHEO diagnosis was 32 years. The initial manifestation of MEN2 was MTC in 60% of patients, synchronous MTC and PHEO in 34%, and PHEO in 6% of patients. Of patients, 72% had bilateral PHEO, and most tumors were synchronous (82%). Subgroup analysis of MEN2 patients with and without PHEO, who were carriers of RET codon 634, the most common mutation with PHEO, showed no significant differences in the stage of MTC at initial diagnosis. The median follow-up time for patients with PHEO was 249 months and without PHEO was 67 months (P < .01). Survival analyses among RET 634 carriers did not show shorter survival for patients with PHEO. The median survival time for patients with PHEO was 499 months and without PHEO was 444 months (P < .05). CONCLUSIONS: PHEO in MEN2 patients are usually bilateral and unlikely to be metastatic. Subgroup analysis of patients with RET 634 mutations with and without PHEO showed that PHEO was not associated with a more advanced stage of MTC at diagnosis or a shorter survival.

Current and future treatments for malignant pheochromocytoma and sympathetic paraganglioma.

Pheochromocytomas (PHs) and sympathetic paragangliomas (SPGs) are rare neuroendocrine tumors. Approximately 17 % of these tumors are malignant, but because no molecular or histologic markers for malignancy exist, patients are often diagnosed with malignant PHs or SPGs after unresectable disease has formed. Patients with progressive metastatic tumors and overwhelming symptoms are currently treated with systemic chemotherapy and radiopharmaceutical agents such as metaiodobenzylguanidine. These therapies lead to partial radiographic response, disease stabilization, and symptomatic improvement in approximately 40 % of patients, and systemic chemotherapy is associated with a modest improvement in overall survival duration. However, over the past decade, substantial progress has been made in clinical, biochemical, and radiographic diagnosis of PHs and SPGs. Approximately 50 % of patients with malignant PHs and SPGs have been found to carry hereditary germline mutations in the succinate dehydrogenase subunit B gene (SDHB), and anti-angiogenic agents such as sunitinib have been found to potentially play a role in the treatment of malignant disease, especially in patients with SDHB mutations. In some patients, treatment with sunitinib has been associated with partial radiographic response, disease stabilization, decreased fluorodeoxyglucose uptake on positron emission tomography, and improved blood pressure control. These findings have led to the development of prospective clinical trials of new targeted therapies for metastatic disease. Here, we provide an updated review of the clinical and genetic predictors of malignant disease, radiographic diagnosis of malignant disease, and information from the most relevant studies of systemic therapies, as well as proposed treatment guidelines for patients with metastatic or potentially malignant PHs and SPGs.

Bone metastases and skeletal-related events in patients with malignant pheochromocytoma and sympathetic paraganglioma.

CONTEXT: Bone metastases (BM) can cause severe pain, spinal cord compression, pathological fractures, and/or hypercalcemia. These skeletal-related events (SREs) may cause immobilization, loss of independence, poor quality of life, and reduced survival. There is limited information on the clinical effects of BM and SREs in patients with malignant pheochromocytoma or sympathetic paraganglioma (PHEO/sPGL). OBJECTIVES: We studied the prevalence and clinical characteristics of BM and SREs in patients with PHEO/sPGL and investigated the risk factors for SRE development. DESIGN: Using a large institutional database, we conducted a retrospective study of 128 patients with malignant PHEO/sPGL at The University of Texas MD Anderson Cancer Center from 1967 through 2011. RESULTS: Of the patients, 91 (71%) had BM, and 57 of these (63%) developed metachronous BM at a median time of 3.4 years (range, 5 months to 23 years) after the primary tumor diagnosis. Metastatic disease was confined exclusively to the skeleton in 26 of 128 (20%) patients. Sufficient information to assess SRE occurrence was available for 67 patients, and 48 of 67 (72%) patients had at least 1 SRE. The median overall survival for the 128 patients was 12 years for patients with only BM, 7.5 years for patients with nonosseous metastases, and 5 years for patients with both BM and nonosseous metastases (log rank test P value = .005). We were unable to identify factors predictive of SRE development, but the occurrence of a first SRE was associated with the development of subsequent SREs in 48% of subjects. In responsive patients, the use of systemic therapy was associated with fewer SREs (P < .0001). CONCLUSIONS: BM and SREs are frequent in patients with malignant PHEO/sPGL. SREs often develop shortly after the diagnosis of BM; severe pain is the most frequent SRE. These patients should be followed long-term by a multidisciplinary team to promptly identify the need for medical or surgical intervention.

A retrospective cohort analysis of the efficacy of adjuvant radiotherapy after primary surgical resection in patients with adrenocortical carcinoma.

CONTEXT: Adrenocortical carcinoma (ACC) is a rare malignancy with high recurrence and mortality rates. The role of adjuvant radiation therapy (RT) to improve outcome remains unclear. OBJECTIVE: The aim of this study was to evaluate the impact of adjuvant RT on overall survival and recurrence rates of ACC patients. DESIGN: We conducted a retrospective cohort study of select ACC patients who were seen at The University of Texas MD Anderson Cancer Center (MDACC) between 1998 and 2011. All patients in this study underwent primary tumor resection and received adjuvant RT within 3 months of primary surgical resection prior to referral to the MDACC. We compared patients who had surgery and adjuvant RT with patients who had surgery alone. RESULTS: Baseline characteristics and adjuvant mitotane use were not significantly different between the adjuvant RT group (n = 16) and the non-RT group (n = 32). Local recurrence occurred in seven patients (43.8%) who received RT and 10 patients (31.3%) in the control group. At 5 yr, the estimated local recurrence-free rate (95% confidence interval) was 53% (32-87%) in the RT group and 67% (52-86%) in the non-RT group (P = 0.53). The distributions of time to distant recurrence and recurrence-free survival were not significantly different between the two groups. Using a multivariate Cox proportional hazards model for overall survival, the hazard ratio for RT use was 1.593 (95% confidence interval, 0.707-3.589; P = 0.26) after adjusting for stage and adjuvant mitotane therapy. CONCLUSIONS: ACC has high rates of recurrence. In our study, RT did not improve clinical outcomes in patients who received their initial care in the community. We believe there is a need for a collaborative, multicenter, prospective randomized trial to evaluate the role of adjuvant treatments (both mitotane and RT) to assess their impact on recurrence patterns and survival.

Treatment with sunitinib for patients with progressive metastatic pheochromocytomas and sympathetic paragangliomas.

CONTEXT: Patients with progressive metastatic pheochromocytomas (PHEOs) or sympathetic paragangliomas (SPGLs) face a dismal prognosis. Current systemic therapies are limited. OBJECTIVES: The primary end point was progression-free survival determined by RECIST 1.1 criteria or positron emission tomography with [(18)F]fluorodeoxyglucose/computed tomography ([(18)F]FDG-PET/CT), in the absence of measurable soft tissue targets. Secondary endpoints were tumor response according to RECIST criteria version 1.1 or FDG uptake, blood pressure control, and safety. DESIGN: We conducted a retrospective review of medical records of patients with metastatic PHEO/SPGL treated with sunitinib from December 2007 through December 2011. An intention-to-treat analysis was performed. PATIENTS AND SETTING: Seventeen patients with progressive metastatic PHEO/SPGLs treated at the Institut Gustave-Roussy and MD Anderson Cancer Center. INTERVENTIONS: Patients treated with sunitinib. RESULTS: According to RECIST 1.1, eight patients experienced clinical benefit; three experienced partial response, and five had stable disease, including four with predominant skeletal metastases that showed a 30% or greater reduction in glucose uptake on [(18)F]FDG-PET/CT. Of 14 patients who had hypertension, six became normotensive and two discontinued antihypertensives. One patient treated with sunitinib and rapamycin experienced a durable benefit beyond 36 months. The median overall survival from the time sunitinib was initiated was 26.7 months with a progression-free survival of 4.1 months (95% confidence interval = 1.4-11.0). Most patients who experienced a clinical benefit were carriers of SDHB mutations. CONCLUSION: Sunitinib is associated with tumor size reduction, decreased [(18)F]FDG-PET/CT uptake, disease stabilization, and hypertension improvement in some patients with progressive metastatic PHEO/PGL. Prospective multi-institutional clinical trials are needed to determine the true benefits of sunitinib.

Clinical benefits of systemic chemotherapy for patients with metastatic pheochromocytomas or sympathetic extra-adrenal paragangliomas: insights from the largest single-institutional experience.

BACKGROUND: The objective of this study was to evaluate the clinical benefits of systemic chemotherapy for patients with metastatic pheochromocytomas or sympathetic paragangliomas by assessing reductions in tumor size and blood pressure and improvements in overall survival (OS). METHODS: The authors retrospectively reviewed the medical records of patients with metastatic pheochromocytomas-sympathetic paragangliomas who had received chemotherapy at The University of Texas MD Anderson Cancer Center. RESULTS: Clinical benefit and OS were assessed. Of 54 patients who received chemotherapy, 52 patients were evaluable for response. Seventeen patients (33%) experienced a response, which was defined as decreased or normalized blood pressure/decreased number and dosage of antihypertensive medications and/or reduced tumor size after the first chemotherapy regimen. The median OS was 6.4 years (95% confidence interval [CI], 5.2-16.4 years) for responders and 3.7 years (95% CI, 3.0-7.5 years) for nonresponders. Among the patients who had synchronous metastatic disease, a positive response at 1 year after the start of chemotherapy was associated with a trend toward longer OS (log-rank test; P = .095). In a multivariate Cox proportional hazards model, the effect of response to chemotherapy on OS was significant (hazard ratio, 0.22; 95% CI, interval: 0.05-1.0; P = .05). All responders had received dacarbazine and cyclophosphamide. Vincristine was included for 14 responders, and doxorubicin was included for 12 responders. The clinical factors that predicted response to chemotherapy could not be identified. CONCLUSIONS: The current results indicted that chemotherapy may decrease tumor size and facilitate blood pressure control in approximately 33% of patients with metastatic pheochromocytoma-sympathetic paraganglioma. These patients exhibited longer survival.

Posterior retroperitoneoscopic adrenalectomy is a safe and effective alternative to transabdominal laparoscopic adrenalectomy for pheochromocytoma.

INTRODUCTION: Laparoscopic adrenalectomy (LA) is a safe minimally invasive approach for treatment of pheochromocytoma (PHEO). Posterior retroperitoneoscopic adrenalectomy (PRA) is an alternative minimally invasive technique; however, there is a lack of data regarding the appropriateness of this approach in patients with PHEO. METHODS: Our endocrine surgery database was queried to identify patients who underwent LA or PRA for PHEO. Patient and tumor characteristics, as well as operative details and postoperative course were compared between the 2 groups. RESULTS: LA or PRA was attempted in 46 patients with PHEO (23 LA, 23 PRA). There were no differences in age, BMI, or tumor size between these groups. PRA was associated with significantly reduced operative times (99 min vs 145 min, P < .001), estimated blood loss (8.4 cc vs 123.8 cc, P = .02), and postoperative length of stay (1.9 nights vs 3.1 nights, P < .01). There was no significant difference in rates of conversion to an open procedure or perioperative complications between these groups. CONCLUSION: LA and PRA are both safe and effective approaches in patients with PHEO. In our experience, PRA results in decreased operative times, blood loss, and postoperative length of stay compared with LA. PRA has become our preferred approach for patients with PHEO.

Novel germline SDHD mutation: diagnosis and implications to the patient.

A 54-year-old man presented with hypertensive crisis. He was found to have bilateral pheochromocytomas and left paraaortic sympathetic paraganglioma. Although he had no family history of paragangliomas or pheochromocytomas, he had been diagnosed with bilateral head and neck paragangliomas 10 years prior. The patient had symptoms of catecholamine excess exacerbated by vanilla ice-cream consumption. Biochemical testing revealed elevated plasma-free metanephrines and chromogranin A levels. Computed tomography showed bilateral carotid body tumors and four reteroperitoneal masses (two in the right adrenal, one in the left adrenal and one in the left paraaortic area). Metaiodobenzylguanidine-SPECT scans showed functional tumors in both the adrenal gland and left paraaortic area. Fluorine 18-fluorodeoxyglucose positron emission tomography did not show any visceral or skeletal metastasis. We carried out gene mutation analysis for succinate dehydrogenase complex subunit B, and succinate dehydrogenase complex subunit D. The patient was diagnosed with hereditary paraganglioma syndrome type 1 with a previously unreported subunit D mutation in exon 3 (c.198G > A, p.W66X). He was treated with phenoxybenzamine at 10 mg/day and with metoprolol at 12.5 mg/day. His blood pressures as well as symptoms of catecholamine excess were controlled. He then underwent bilateral adrenalectomy and reteroperitoneal dissection. His blood pressure normalized and he discontinued antihypertensive medications after surgery. He is currently on replacement therapy with hydrocortisone and fludrocortisone.

Clinical risk factors for malignancy and overall survival in patients with pheochromocytomas and sympathetic paragangliomas: primary tumor size and primary tumor location as prognostic indicators.

CONTEXT: Pheochromocytomas and sympathetic paragangliomas are rare neuroendocrine tumors for which no precise histological or molecular markers have been identified to differentiate benign from malignant tumors. OBJECTIVE: The aim was to determine whether primary tumor location and size are associated with malignancy and decreased survival. DESIGN AND SETTING: We performed a retrospective chart review of patients with either pheochromocytoma or sympathetic paraganglioma. PATIENTS: The study group comprised 371 patients. MAIN OUTCOME MEASURES: Overall survival and disease-specific survival were analyzed according to tumor size and location. RESULTS: Sixty percent of patients with sympathetic paragangliomas and 25% of patients with pheochromocytomas had metastatic disease. Metastasis was more commonly associated with primary tumors located in the mediastinum (69%) and the infradiaphragmatic paraaortic area, including the organ of Zuckerkandl (66%). The primary tumor was larger in patients with metastases than in patients without metastatic disease (P < 0.0001). Patients with sympathetic paragangliomas had a shorter overall survival than patients with pheochromocytomas (P < 0.0001); increased tumor size was associated with shorter overall survival (P < 0.001). Patients with sympathetic paragangliomas were twice as likely to die of disease than patients with pheochromocytomas (hazard ratio = 1.93; 95% confidence interval = 1.20-3.12; P = 0.007). As per multivariate analysis, the location of the primary tumor was a stronger predictor of metastases than was the size of the primary tumor. CONCLUSIONS: The size and location of the primary tumor were significant clinical risk factors for metastasis and decreased overall survival duration. These findings delineate the follow-up and treatment for these tumors.

A catecholamine crisis on Mount Kilimanjaro: a hypoxia effect?

Sympathetic paragangliomas are autonomic nervous system tumors associated with dysregulation of intracellular oxygen metabolism. Exposure to high altitudes is reported to activate the production of catecholamines in the sympathoadrenal system. We describe an individual with a paraganglioma complicated by a catecholamine crisis that occurred on the summit of Mount Kilimanjaro.

Fatal hypoglycemia in malignant pheochromocytoma: direct glucose consumption as suggested by (18)F-2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography imaging.

We present a patient with metastatic pheochromocytoma, who developed progressive and fatal hypoglycemia most likely secondary to direct tumor glucose consumption that did not respond to high-dose glucose infusion, corticosteroids, or glucagon therapy. The pattern of glucose uptake on (18)F-2-fluoro-2-deoxy-D-glucose positron emission tomography, with preferential tumor glucose uptake in association with a marked reduction in normal uptake in the heart, muscles, and brain, is highly suggestive of direct consumption of glucose by the tumor rather than insulin-like growth factor-2 mediated hypoglycemia. In patients with large-volume metastatic malignancies, direct tumor glucose consumption should be considered in the differential diagnosis of hypoglycemia. Nuclear medicine imaging techniques can illustrate the pathophysiology of hypoglycemia in such cases.

Paraganglioma syndrome type 1 in a patient with Carney-Stratakis syndrome.

BACKGROUND: A 33-year-old man was referred to a specialist center with a left neck mass and hypertension. The patient underwent surgery, which confirmed a malignant neck paraganglioma with metastasis to a cervical lymph node. He had no family history of carotid body tumors or pheochromocytoma. INVESTIGATIONS: Measurements of plasma free metanephrines and chromogranin A; radiographic evaluations with CT, (18)F-fluorodeoxyglucose PET and (123)I-labeled metaiodobenzylguanidine scan; gene analysis for mutations in the SDHD and the KIT gene. DIAGNOSIS: Paraganglioma syndrome type 1 in a patient with a paraganglioma, bilateral pheochromocytomas and a gastrointestinal stromal tumor with a somatic Asp579del KIT mutation. MANAGEMENT: The patient underwent surgical excision of all tumors after adequate preparation with alpha and beta blockers. Blood pressure normalized after surgery. The patient is examined regularly with biochemical and radiographic studies, and his follow-up is expected to last throughout life.

Proctocolectomía total con anastamosis ileo-anal de reservorio en "J"- Experiencia en el Instituto Nacional de la Nutrición Salvador Zubirán / Total proctocolectomy with ileal pouch anal anastomosis. Experience at the Instituto Nacional de la Nutricion Zubiran in Mexico

Antecedentes. La proctocolectomía total y anastomosis ileo-anal (PCTAIA) es el procedimiento de elección para los pacientes con colitis ulcerativa crónica inespecífica y poliposis adenomatosa familiar que requieren cirugía. La frecuencia de presentación de estas enfermedades es baja en México, por lo que la experiencia con este procedimiento es escasa. Objetivo. Analizar la morbi-mortalidad operatoria y resultados funcionales a largo plazo en una serie de pacientes sometidos a esta operación en un hospital de referencia en México. Material y métodos. Se analizan retrospectivamente 44 pacientes consecutivos operados de PCTAIA entre 1987 y 1997. La operación incluyó resección mucosa de la zona de transición, anastomosis manual del reservorio ileal en "J" e ileostomía temporal en todos los pacientes. Se determinaron las causas y cifras de morbilidad y mortalidad posoperatorias, así como los resultados funcionales y complicaciones a largo plazo. Resultados. La edad promedio fue de 33 ñ 15 años. Hubo 23 mujeres (52 por ciento) y 21 hombres (48 por ciento). Los principales diagnósticos fueron colitis ulcerativa crónica inespecífica en 59 por ciento y poliposis adenomatosa familiar en 36 por ciento. La morbilidad global fue del 39 por ciento y la mortalidad del 2 por ciento. Con un seguimiento promedio de 24 meses, el promedio de evacuaciones diurnas que presentaron los pacientes fue de 4, 10 por ciento presentaron escurrimiento diurno, 30 por ciento escurrimiento nocturno, y ninguno presentó incontinencia. Tres pacientes han presentado inflamación del reservorio, con respuesta adecuada a antibióticos. Dos pacientes han presentado fístulas del reservorio ileal a largo plazo, pero ninguno requirió de su resección. Conclusiones. PCTAIA es una operación factible en nuestro medio que se acompaña de cifras aceptable de morbi-mortalidad y resultados funcionales satisfactorios