Expression of somatostatin receptors in hemangioblastomas associated with von Hippel-Lindau disease as a novel diagnostic, therapeutic, and follow-up opportunity: A case report and literature review.

Hemangioblastomas associated with von Hippel-Lindau (VHL) disease are frequently multiple and recur during prolonged follow-up. Currently, no systemic treatment is available for these tumors. Recent studies have shown the expression of somatostatin receptors in these types of hemangioblastomas. Notably, increased somatostatin receptor expression in a tumor, as determined by peptide-receptor radionuclide imaging, is a predictive factor of response to treatment with somatostatin analogs and peptide-receptor radionuclide therapy. The aim of this study was to describe the case of a patient with increased expression of somatostatin receptors in a suprasellar hemangioblastoma associated with VHL disease and conduct a literature review on somatostatin receptor expression in patients with VHL-associated hemangioblastomas. We describe herein the case of a 51-year-old man with VHL disease who had a suprasellar hemangioblastoma detected on magnetic resonance imaging. Peptide-receptor radionuclide imaging using gallium-68-DOTATOC (68Ga-DOTATOC) identified increased expression of somatostatin receptors in the suprasellar hemangioblastoma, along with multiple pancreatic neuroendocrine tumors and bilateral pheochromocytomas. The patient was treated for 1 year with lanreotide, a somatostatin analog. A repeat 68Ga-DOTATOC 1 year after starting lanreotide revealed decreased radiotracer uptake by the hemangioblastoma, consistent with a metabolic response. The presence of somatostatin receptors in hemangioblastomas associated with VHL disease is a novel finding. The decreased expression of these receptors after treatment with a somatostatin analog, as described in the present case, positions the somatostatin receptor as a new target for novel diagnostic, therapeutic, and follow-up opportunities in patients with VHL disease.

Expression of somatostatin receptors in hemangioblastomas associated with von Hippel-Lindau disease as a novel diagnostic, therapeutic, and follow-up opportunity: A case report and literature review

SUMMARY Hemangioblastomas associated with von Hippel-Lindau (VHL) disease are frequently multiple and recur during prolonged follow-up. Currently, no systemic treatment is available for these tumors. Recent studies have shown the expression of somatostatin receptors in these types of hemangioblastomas. Notably, increased somatostatin receptor expression in a tumor, as determined by peptide-receptor radionuclide imaging, is a predictive factor of response to treatment with somatostatin analogs and peptide-receptor radionuclide therapy. The aim of this study was to describe the case of a patient with increased expression of somatostatin receptors in a suprasellar hemangioblastoma associated with VHL disease and conduct a literature review on somatostatin receptor expression in patients with VHL-associated hemangioblastomas. We describe herein the case of a 51-year-old man with VHL disease who had a suprasellar hemangioblastoma detected on magnetic resonance imaging. Peptide-receptor radionuclide imaging using gallium-68-DOTATOC (68Ga-DOTATOC) identified increased expression of somatostatin receptors in the suprasellar hemangioblastoma, along with multiple pancreatic neuroendocrine tumors and bilateral pheochromocytomas. The patient was treated for 1 year with lanreotide, a somatostatin analog. A repeat 68Ga-DOTATOC 1 year after starting lanreotide revealed decreased radiotracer uptake by the hemangioblastoma, consistent with a metabolic response. The presence of somatostatin receptors in hemangioblastomas associated with VHL disease is a novel finding. The decreased expression of these receptors after treatment with a somatostatin analog, as described in the present case, positions the somatostatin receptor as a new target for novel diagnostic, therapeutic, and follow-up opportunities in patients with VHL disease.

PANCREATODUODENECTOMY IN PATIENT WITH VON HIPPEL-LINDAU DISEASE: A LITERATURE REVIEW.

BACKGROUND: The von Hippel-Lindau disease is a highly penetrant autosomal dominant syndrome characterized by tumor predisposition in different organs. AIM: This study aimed to describe a case of a pancreatoduodenectomy for a 30-year-old male patient with von Hippel-Lindau disease. METHODS: We present a case study and the literature review aiming at the state-of-the-art management of a patient with pheochromocytoma, capillary hemangioblastoma in the peripheral retina, and two neuroendocrine tumors in the pancreas. RESULTS: A larger pancreatic lesion was located in the uncinate process, measuring 31 mm. The smaller lesion was located in the proximal pancreas and was detected only on the positron emission tomography-computed tomography scan with DOTATOC-68Ga. Genetic investigation revealed a mutation in the locus NM_000551.3 c.482G>A (p.Arg161Gln) of the Von Hippel-Lindau Human Suppressor gene. The uncinate process tumor was larger than 30 mm and the patient had a mutation on exon 3; therefore, we indicated a pancreatoduodenectomy involving the proximal pancreas to resect both tumors en bloc. During the postoperative period, the patient presented a peripancreatic fluid collection, which was treated as a grade B pancreatic fistula with clinical resolution of the complication. On postoperative day 21, he was discharged home. CONCLUSION: The management of patients with von Hippel-Lindau disease and pancreatic neuroendocrine tumors is complex and must be centered on tertiary institutions with a large volume of pancreatic surgery. Although the current literature assists in decision-making in most situations, each step of the treatment requires analysis and discussion between different medical specialties, including surgeons, clinicians, radiologists, and anesthesiologists.

Pancreatoduodenectomy in patient with von hippel-lindau disease: a literature review / Pancreaticoduodenectomia em paciente com doença de von hippel-lindau - revisão da literatura

ABSTRACT BACKGROUND: The von Hippel-Lindau disease is a highly penetrant autosomal dominant syndrome characterized by tumor predisposition in different organs. AIM: This study aimed to describe a case of a pancreatoduodenectomy for a 30-year-old male patient with von Hippel-Lindau disease. METHODS: We present a case study and the literature review aiming at the state-of-the-art management of a patient with pheochromocytoma, capillary hemangioblastoma in the peripheral retina, and two neuroendocrine tumors in the pancreas. RESULTS: A larger pancreatic lesion was located in the uncinate process, measuring 31 mm. The smaller lesion was located in the proximal pancreas and was detected only on the positron emission tomography-computed tomography scan with DOTATOC-68Ga. Genetic investigation revealed a mutation in the locus NM_000551.3 c.482G>A (p.Arg161Gln) of the Von Hippel-Lindau Human Suppressor gene. The uncinate process tumor was larger than 30 mm and the patient had a mutation on exon 3; therefore, we indicated a pancreatoduodenectomy involving the proximal pancreas to resect both tumors en bloc. During the postoperative period, the patient presented a peripancreatic fluid collection, which was treated as a grade B pancreatic fistula with clinical resolution of the complication. On postoperative day 21, he was discharged home. CONCLUSION: The management of patients with von Hippel-Lindau disease and pancreatic neuroendocrine tumors is complex and must be centered on tertiary institutions with a large volume of pancreatic surgery. Although the current literature assists in decision-making in most situations, each step of the treatment requires analysis and discussion between different medical specialties, including surgeons, clinicians, radiologists, and anesthesiologists.

RESUMO RACIONAL: A doença de von Hippel Lindau é uma síndrome autossômica dominante que se caracteriza por maior incidência de tumores em diferentes órgãos. OBJETIVO: Descrever um caso de pancreatoduodenectomia em paciente do sexo masculino de 30 anos com von Hippel Lindau. MÉTODO: Apresentamos o caso e a revisão da literatura realizada para otimizar o manejo do paciente, que apresentava feocromocitoma, hemangioblastoma capilar na retina periférica e dois tumores neuroendócrinos no pâncreas. RESULTADOS: O maior tumor pancreático localizava-se no processo uncinado medindo 31 mm. A lesão menor estava localizada no corpo proximal do pâncreas e foi detectada apenas na tomografia computadorizada por emissão de pósitrons com DOTATOC-68Ga. A investigação genética revelou uma mutação no locus NM_000551.3 c.482G>A (p.Arg161Gln) do gene supressor humano de Von Hippel-Lindau. O tumor no processo era maior que 30mm e o paciente apresentava mutação no exon 3. Indicamos pancreatoduodenectomia envolvendo o corpo proximal do pâncreas para ressecar em bloco ambos os tumores. No pós-operatório o paciente apresentou coleção líquida peripancreática que foi tratada como fístula pancreática grau B, com resolução clínica da complicação. Ele recebeu alta hospitalar no vigésimo primeiro dia pós-operatório. CONCLUSÕES: o manejo de pacientes com doença de von Hippel Lindau e tumores neuroendócrinos pancreáticos é complexo e deve ser centrado em instituições terciárias com grande volume de cirurgia pancreática. Embora a literatura atual auxilie na tomada de decisão na maioria das situações, cada etapa do tratamento requer análise e discussão entre diferentes especialidades médicas, incluindo cirurgiões, clínicos, radiologistas e anestesiologistas.

Colonic tuberculosis presenting as intestinal subocclusion in a patient with neuroendocrine tumor: a case report.

Extra-pulmonary tuberculosis (EPT) is responsible for approximately 14% of all tuberculosis cases in Brazil. The incidence of EPT is increasing slightly and is often associated with human immunodeficiency virus infection and other causes of immunosuppression. The association of EPT and cancer is poorly documented. Here we present a rare case of intestinal subocclusion that was supposed to be caused by cancer and was caused by colonic tuberculosis (CT) in a patient with metastatic neuroendocrine tumor (NET). A 61-year-old woman presented with one-year history of abdominal pain, diarrhea and weight loss. An abdominal CT scan (ACTS) showed liver, peritoneal and lymph nodes metastasis. Colonoscopy revealed a subocclusive lesion in the descendent colon. She underwent an urgent laparoscopy and transverse colostomy. The liver biopsy revealed a well differentiated grade 2 NET and the mycobacterial culture confirmed tuberculosis in the colonic lesion. Anti-tuberculosis was prescribed, and somatostatin analogue therapy was introduced one month later. The tuberculosis treatment was finished, and the patient remained on somatostatin analogue for 21 months. During this time the symptoms of abdominal pain and diarrhea disappeared and her body weight increased 35% over her baseline weight. Then, diarrhea, flushing and abdominal pain returned, and a new ACTS confirmed progressive disease. Interferon was added to her treatment with satisfactory control of symptoms. She was forwarded to another hospital to be treated with 177Lu-DOTATOC. The symptoms improved and the patient remained symptom free for more than a year, and now she has a new disease progression. The patient will be evaluated for retreatment with 177Lu-DOTATOC. Advanced NET may be a devastating disease enough to predispose the patient to EPT. We must keep this hypothesis in the differential diagnosis of our patients since symptoms of CT are usually nonspecific. At colonoscopy, radiological features are strictures, colitis and polypoidal lesions and complications such as bowel perforation or fistula must be in mind. It is particularly important those with advanced disease in endemic areas of tuberculosis.

Multiple endocrine neoplasia type 1 in patients with gastroenteropancreatic neuroendocrine tumors: An opportunity for early diagnosis and appropriate management.

Gastroenteropancreatic neuroendocrine tumors (GEPNET) are rare tumors that may be sporadic or develop as part of multiple endocrine neoplasia type 1 syndrome (MEN1). The aim of the present study was to report the experience of a Brazilian multidisciplinary outpatient neuroendocrine tumor clinic regarding the clinical diagnosis of MEN1 in a cohort of GEPNET patients. Patient data, including clinical characteristics and the lag time from the onset of symptoms to diagnosis of the first tumor, and further lag time until the diagnosis of MEN1, were retrospectively reviewed. Among 44 GEPNET patients, 6 had a clinical diagnosis of MEN1. Primary hyperparathyroidism and GEPNET were present in all patients in the cohort, and pituitary neuroendocrine tumors were present in 33.3%. The median time interval from the onset of initial symptoms to the diagnosis of the first tumor was 42 months (range, 0-204 months). The median time interval between the diagnosis of the first tumor and the diagnosis of MEN1 was 22 months (range, 1-109 months). The prolonged lag time between the onset of initial symptoms and MEN1 diagnosis may result in substantial morbidity and loss of opportune interventions for the patients. Therefore, greater efforts should be made to shorten these times and improve the care of patients with MEN1.

Gastrinoma of Cystic Duct: A Rare Association With Multiple Endocrine Neoplasia Type 1.

Neuroendocrine tumors (NETs) of cystic duct are extremely rare, accounting for less than 2% of NET cases. The association of biliary tree NET and multiple endocrine neoplasm type 1 (MEN1) are even more rare. In this report, we described a case of a 65-year-old woman who was referred to our neuroendocrine outpatient clinic to investigate MEN1 after an incidental diagnosis of gastrinoma. Her medical history initiated 7 years earlier with severe peptic disease not responsive to proton pump inhibitor therapy. Endoscopic study revealed erosive antral gastritis, erosive duodenitis, bulbar ulcer and pyloric deformity. During follow-up she presented with abdominal pain, chronic diarrhea and weight loss; an ultrasonography was performed and showed only a cholelithiasis. She underwent a video laparoscopic cholecystectomy and all her symptoms were solved. Histopathological study found a 1.0 cm well differentiated NET (Ki-67 labeling index < 2%) located in cystic duct infiltrating the entire wall and subserosa. The MEN1 investigation revealed a primary hyperparathyroidism with a brown tumor in right iliac bone; the patient was referred to a total parathyroidectomy with autotransplantation. No evidence of pituitary tumor was found. The patient remains asymptomatic 24 months after surgery. To conclude, this case highlights an unusual presentation of a cystic duct primary NET gastrinoma in a MEN1 context.

Psychometric properties of the multidimensional fatigue inventory in Brazilian Hodgkin's lymphoma survivors.

CONTEXT: Fatigue is the most common symptom among Hodgkin's lymphoma survivors. OBJECTIVES: To evaluate the psychometric properties of the Brazilian version of the Multidimensional Fatigue Inventory (MFI). METHODS: The MFI was translated into Brazilian Portuguese using established forward-backward translation procedures, and the psychometric properties were evaluated in a sample of 200 Hodgkin's lymphoma survivors. The psychometric properties evaluated included internal consistency and construct validity. The MFI was administered along with the informed consent form. RESULTS: The overall Cronbach's alpha coefficient for the 20 items was 0.84, ranging from 0.59 to 0.81 for each of the five scales. Correlations between items and scales ranged from 0.32 to 0.72. The factor analysis yielded a five-factor solution that explained 65% of the variance. The first factor merged the original "general fatigue" and "physical fatigue" scales, as has been previously reported. The second factor identified the original "mental fatigue" scale and the fifth factor identified the original "reduced activity" scale. Questions from the original "reduced motivation" scale were represented in both factors three and four. CONCLUSION: The Brazilian version of the MFI showed satisfactory psychometric properties and can be considered a valid research tool for assessing cancer-related fatigue.

Validation of the Brazilian Portuguese version of the Medical Outcomes Study-Social Support Survey in Hodgkin's lymphoma survivors.

PURPOSE: The aim of this study was to assess the psychometric properties of the Brazilian Portuguese version of the "Medical Outcomes Study-Social Support Survey (MOS-SSS)" in Hodgkin's lymphoma (HL) survivors. METHODS: The MOS-SSS is a 19-item questionnaire with five scales covering different aspects of social support (affection, positive social interaction, emotional, informational, and material). A sample of 200 HL survivors completed a self-administered questionnaire at the treatment center or at home. RESULTS: The median age of the patients at diagnosis was 29 years (16­77), and the median follow-up since diagnosis was 7 years (3.6-12.7). Item-corrected Pearson correlation coefficients between items and their dimensions varied from 0.57 to 0.76. Internal consistency, evaluated using Cronbach's alpha, was 0.95 for the overall scale, ranging from 0.78 to 0.87 for the five subscales proposed by the original instrument. An exploratory factor analysis yielded a three-factor solution, aggregating affection and positive social interaction, and emotional and informational dimensions of social support. Higher socioeconomic status and higher social network were associated with higher levels of all kinds of support. CONCLUSION: Results show good general psychometric properties of the Brazilian version of the MOS-SSS when applied to HL survivors. The three-factor structure identified in this study is in line with a previous validation among Brazilian healthy civil servants. The Brazilian Portuguese version will now be used to evaluate social support and its association with long-term disease outcomes and quality of life of Hodgkin's lymphoma survivors.

Brazilian version of the QLQ-LC13 lung cancer module of the European Organization for Research and Treatment of Cancer: preliminary reliability and validity report.

This study reports the reliability and validity of the Brazilian Portuguese version of QLQ-LC13. After translation and cross-cultural adaptation, the questionnaire was administered, together with the QLQ-C30 core questionnaire, to 82 patients with lung cancer. The analysis was based on 60 patients who completed two interviews, and who received chemotherapy alone or in combination with radiotherapy. The reliability or internal consistency of dyspnea scale was 0.79. The pain scale needed to be combined with the QLQ-C30 pain items to reach a satisfactory value of 0.73. The construct validity was supported by the ability of the questionnaire to discriminate patients regarding their performance status and type of treatment. However, the change over time, although in the expected direction for all items, was statistically significant in four of the 10 items studied. The criterion-related validity was supported by the statistically significant correlation between all four side effect items and the physicians' reports of toxicity, while the evolutive changes in the performance status were statistically significant in only four items. Most psychometric properties of the Brazilian version of the QLQ-LC13 were adequately supported in this analysis. However, a wider utilization of this module is necessary to fully ascertain its reliability and validity properties.

Rabdomiossarcoma: avaliaçäo do protocolo IRS III utilizado no Hospital do Câncer (INCA), Rio de Janeiro 1988-1993 / Rhabdomyosarcoma: evaluation of IRS III protocol used in Cancer Hospital (INCA), Rio de Janeiro 1988-1993

Foram estudados 39 casos de pacientes menores de 21 anos portadores de rabdomiossarcoma matriculados no Hospital do Câncer entre 1988 a 1993. O estudo baseia-se no protocolo IRS III (Intergroup Rhabdomyosarcoma Study III) quanto aos regimes terapêuticos utilizados, a distribuiçÝo por sítios primários, histologia, grupos e estadios. As curvas de sobrevida foram determinadas para dois grupos e momentos distintos. O primeiro grupo incluiu todos os pacientes, o momento zero foi considerado como o do início do tratamento e o evento final, a data da última observaçÝo. Para o segundo grupo foi considerado como momento zero o término do tratamento para aqueles pacientes que se encontravam em remissÝo completa, e como o evento final o momento da recidiva ou da última observaçÝo para aqueles que ainda permaneciam sem evidências de doença. Foi utilizado o Método de Kaplan-Meier. A toxicidade apresentada foi considerada de moderna intensidade, nÝo ocasionando óbitos. A sobrevida de 7 anos foi de 49,2 porcento para o primeiro grupo com tempo de acompanhamento mediano de 29 meses; a do segundo grupo, constituída de 21 pacientes, foi de 78 porcento em 6 anos, com tempo de acompanhamento mediano de 32 meses. Dada a alta freqüência de casos considerados avançados ao diagnóstico (92 porcento) concluímos: que os resultados apresentados sÝo similares àqueles apresentados pela literatura internacional e que os regimes foram seguros em sua aplicabilidade.