Neuroendocrine Tumor Heterogeneity Adds Uncertainty to the World Health Organization 2010 Classification: Real-World Data from the Spanish Tumor Registry (R-GETNE).

BACKGROUND: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a complex family of tumors of widely variable clinical behavior. The World Health Organization (WHO) 2010 classification provided a valuable tool to stratify neuroendocrine neoplasms (NENs) in three prognostic subgroups based on the proliferation index. However, substantial heterogeneity remains within these subgroups, and simplicity sometimes entails an ambiguous and imprecise prognostic stratification. The purpose of our study was to evaluate the prognostic impact of histological differentiation within the WHO 2010 grade (G) 1/G2/G3 categories, and explore additional Ki-67 cutoff values in GEP-NENs. SUBJECTS, MATERIALS, AND METHODS: A total of 2,813 patients from the Spanish National Tumor Registry (RGETNE) were analyzed. Cases were classified by histological differentiation as NETs (neuroendocrine tumors [well differentiated]) or NECs (neuroendocrine carcinomas [poorly differentiated]), and by Ki-67 index as G1 (Ki-67 <2%), G2 (Ki-67 3%-20%), or G3 (Ki-67 >20%). Patients were stratified into five cohorts: NET-G1, NET-G2, NET-G3, NEC-G2, and NEC-G3. RESULTS: Five-year survival was 72%. Age, gender, tumor site, grade, differentiation, and stage were all independent prognostic factors for survival. Further subdivision of the WHO 2010 grading improved prognostic stratification, both within G2 (5-year survival: 81% [Ki-67 3%-5%], 72% [Ki-67 6%-10%], 52% [Ki-67 11%-20%]) and G3 NENs (5-year survival: 35% [Ki-67 21%-50%], 22% [Ki-67 51%-100%]). Five-year survival was significantly greater for NET-G2 versus NEC-G2 (75.5% vs. 58.2%) and NET-G3 versus NEC-G3 (43.7% vs. 25.4%). CONCLUSION: Substantial clinical heterogeneity is observed within G2 and G3 GEP-NENs. The WHO 2010 classification can be improved by including the additive effect of histological differentiation and the proliferation index. IMPLICATIONS FOR PRACTICE: Gastroenteropancreatic neuroendocrine neoplasms are tumors of widely variable clinical behavior, roughly stratified by the World Health Organization (WHO) 2010 classification into three subgroups based on proliferation index. Real-world data from 2,813 patients of the Spanish Registry RGETNE demonstrated substantial clinical heterogeneity within grade (G) 2 and G3 neuroendocrine neoplasms. Tumor morphology and further subdivision of grading substantially improves prognostic stratification of these patients and may help individualize therapy. This combined, additive effect shall be considered in future classifications of neuroendocrine tumors and incorporated for stratification purposes in clinical trials.

Novel equation to determine the hepatic triglyceride concentration in humans by MRI: diagnosis and monitoring of NAFLD in obese patients before and after bariatric surgery.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is caused by abnormal accumulation of lipids within liver cells. Its prevalence is increasing in developed countries in association with obesity, and it represents a risk factor for non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma. Since NAFLD is usually asymptomatic at diagnosis, new non-invasive approaches are needed to determine the hepatic lipid content in terms of diagnosis, treatment and control of disease progression. Here, we investigated the potential of magnetic resonance imaging (MRI) to quantitate and monitor the hepatic triglyceride concentration in humans. METHODS: A prospective study of diagnostic accuracy was conducted among 129 consecutive adult patients (97 obesity and 32 non-obese) to compare multi-echo MRI fat fraction, grade of steatosis estimated by histopathology, and biochemical measurement of hepatic triglyceride concentration (that is, Folch value). RESULTS: MRI fat fraction positively correlates with the grade of steatosis estimated on a 0 to 3 scale by histopathology. However, this correlation value was stronger when MRI fat fraction was linked to the Folch value, resulting in a novel equation to predict the hepatic triglyceride concentration (mg of triglycerides/g of liver tissue = 5.082 + (432.104 * multi-echo MRI fat fraction)). Validation of this formula in 31 additional patients (24 obese and 7 controls) resulted in robust correlation between the measured and estimated Folch values. Multivariate analysis showed that none of the variables investigated improves the Folch prediction capacity of the equation. Obese patients show increased steatosis compared to controls using MRI fat fraction and Folch value. Bariatric surgery improved MRI fat fraction values and the Folch value estimated in obese patients one year after surgery. CONCLUSIONS: Multi-echo MRI is an accurate approach to determine the hepatic lipid concentration by using our novel equation, representing an economic non-invasive method to diagnose and monitor steatosis in humans.

Metástasis pancreáticas por carcinoma renal. Nuestra casuística y revisión de la literatura / Pancreatic metastases due to renal carcinoma. Our cases and a literature review

Analizar los casos de metástasis pancreáticas por carcinoma renal intervenidos en nuestro hospital entre los años 2000 y 2011.Material y métodos Estudio retrospectivo donde se recogen diferentes variables de 8 pacientes con metástasis pancreáticas por carcinoma renal intervenidos. Comparación de nuestros datos con los de la literatura. Resultados La enfermedad metastásica del páncreas por carcinoma renal en nuestra serie ha sido de 1,2%. Todas las metástasis han sido metacrónicas. La afectación por sexo ha sido igual. El tiempo medio entre la resección del tumor renal y el diagnóstico de las metástasis ha sido de 12,42 años (rango: 1,62-30,13 años). La actitud terapéutica ante las lesiones pancreáticas ha sido quirúrgica en todos los casos. Hasta la fecha, 7 pacientes continúan vivos. Conclusión La enfermedad metastásica del páncreas por carcinoma renal es poco frecuente (1-2,8%). El intervalo entre la resección primaria y las metástasis puede ser bastante largo. Siempre debe sospecharse metástasis pancreática en los pacientes que presenten masa pancreática e historia de carcinoma renal. Se recomienda un tratamiento quirúrgico agresivo en casos seleccionados. La cirugía en estos casos mejora la supervivencia y la calidad de vida (AU)

Objective: To analyse the cases of pancreatic metastases due to renal carcinoma operated on in our hospital between the years 2000 and 2011.Material and methods: A retrospective study using the variables of 8 patients who were subjected to surgery of pancreatic metastases due to renal carcinoma, and a comparison of our data with those from the literature. Results: The incidence of metastatic disease of the pancreas due to renal carcinoma in our series was 1.2%. All the metastases were metachronous, with both sexes being affected equally. The mean time between resection of the renal tumour and the diagnosis of the metastasis was 12.42 years (range: 1.62-30.13 years). The therapeutic approach to the pancreatic lesions was surgical in all cases. Seven patients are currently still alive. Conclusion: Metastatic disease of the pancreas due to renal carcinoma is uncommon(1%-2.8%). The interval between the primary resection and the metastasis can be quite long. Pancreatic metastasis must always be suspected in patients who present with a pancreatic mass and a history of renal carcinoma. Aggressive surgical treatment is recommended in selected cases. The surgery in these cases improves survival and the quality of life (AU)

[Pancreatic metastases due to renal carcinoma. Our cases and a literature review]. / Metástasis pancreáticas por carcinoma renal. Nuestra casuística y revisión de la literatura.

OBJECTIVE: To analyse the cases of pancreatic metastases due to renal carcinoma operated on in our hospital between the years 2000 and 2011. MATERIAL AND METHODS: A retrospective study using the variables of 8 patients who were subjected to surgery of pancreatic metastases due to renal carcinoma, and a comparison of our data with those from the literature. RESULTS: The incidence of metastatic disease of the pancreas due to renal carcinoma in our series was 1.2%. All the metastases were metachronous, with both sexes being affected equally. The mean time between resection of the renal tumour and the diagnosis of the metastasis was 12.42 years (range: 1.62-30.13 years). The therapeutic approach to the pancreatic lesions was surgical in all cases. Seven patients are currently still alive. CONCLUSION: Metastatic disease of the pancreas due to renal carcinoma is uncommon (1%-2.8%). The interval between the primary resection and the metastasis can be quite long. Pancreatic metastasis must always be suspected in patients who present with a pancreatic mass and a history of renal carcinoma. Aggressive surgical treatment is recommended in selected cases. The surgery in these cases improves survival and the quality of life.

Effect of neoadjuvant chemotherapy in hepatic steatosis.

UNLABELLED: Chemotherapy drugs often produce side effects in the liver. In recent years, there has been speculation about the ability to produce hepatic steatosis in patients treated with 5-fluorouracil and oxaliplatin. This prospective study examines whether these drugs can produce steatosis in patients with neoadjuvant treatment who were operated on for liver tumors. PURPOSE: Our objective was to assess the effect of neoadjuvant chemotherapy (NAC) on the development of hepatic steatosis in the healthy liver. PATIENTS AND METHODS: This was a prospective study based on 32 patients divided into two groups. The presence of steatosis was assessed using a histological score (Kleiner classification) and a biochemical method (Folch method) for patients from both groups. RESULTS: A total of 14 patients (44%) had hepatic steatosis and half of these were in each group. The steatosis was moderate to severe (grades 2-3) in 4 patients (13%), 2 in each group. The mean levels of triglycerides in the liver were 33.38 and 29.94 mg/g in group I and group II, respectively, with the difference not being statistically significant. CONCLUSIONS: Almost half of the patients treated with NAC for liver neoplasia developed steatosis. Nevertheless, NAC does not seem to increase the risk of hepatic steatosis.

Características clínicas y moleculares de una familia con síndrome de neoplasia endocrina múltiple tipo 1 / Clinical and molecular features in a family with multiple endocrine neoplasia type-1 syndrome

INTRODUCCIÓN: Los rasgos clínicos del síndrome de neoplasia endocrina múltiple tipo 1 (NEM-1) son: hiperplasia o adenoma de las glándulas paratiroides, adenoma hipofisario y tumores endocrinos gastroenteropancreáticos. Se debe a mutaciones del gen MEN1, localizado en la región q13 del cromosoma 11. El pronóstico de los pacientes depende del crecimiento tumoral y de su potencial metastático.PACIENTES Y MÉTODO: Se revisan las historias clínicas de los miembros de esta familia (6 varones y 2 mujeres) con NEM-1 diagnosticados entre 1995 y 2007 en el Hospital Donostia de San Sebastián. El estudio familiar de todos los pacientes y familiares (19 casos de 2 generaciones) se hizo en dos fases. La primera, mediante técnica de cribado de mutaciones y la segunda, por multiplex ligation-dependent probe amplification (MLPA)para detectar deleciones del gen.RESULTADOS: El cribado de mutaciones no permitió identificar ninguna variante patogénica en el probando de esta familia. El estudio mediante MLPA reveló una deleción que afectaba al exón 1 y 2 del gen MEN1. De los 10 familiares con esta alteración molecular, 8 presentaron algún rasgo fenotipico del síndrome (8 con hiperparatiroidismo, 2 con prolactinomas y 3 con gastrinomas) tras 12 años de seguimiento.CONCLUSIÓN: Se comentan las formas clínicas del síndromeNEM-1 en esta familia y la alteración molecular encontrada. El estudio de deleciones del gen MEN1 debería incorporarse al cribado molecular sistemático

BACKGROUND: The clinical features of multiple endocrineneoplasia type-1 (MEN-1) syndrome are hyperplasia or adenoma of the parathyroid glands, pituitary adenoma and gastroenteropancreatic endocrine tumors. This syndrome isdue to mutations in the MEN1 gene, located on the q13 region of chromosome 11. Prognosis depends on tumoralgrowth and metastatic potential.PATIENTS AND METHOD: We reviewed the medical records ofthe members of a family (6 men and 2 women) with MEN-1syndrome diagnosed between 1995 and 2007 in Hospital Donostia, San Sebastian (Spain). Familial study of all patients and family members (19 cases from 2 generations) was performed in 2 phases. The first phase consisted of mutation screening and the second of multiplex ligation-dependent probe amplification (MLPA) to detect deletions.RESULTS: Screening of mutations identified no pathogenicvariants in the proband of this family. MLPA revealed a deletion affecting exons 1 and 2 of the MEN1 gene. Of the 10 family members with this molecular alteration, 8 had at least one phenotypic feature of this syndrome (hyperparathyroidism in 8, prolactinomas in 2, and gastrinomas in 3) after 12 years of follow-up.CONCLUSION: We discuss the clinical forms of MEN-1 syndrome in this family and the molecular alteration found. Study of MEN1 gene deletions should be incorporated into routine molecular screening

Papilomatosis biliar difusa / Diffuse biliary papillomatosis

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[Clinical and molecular features in a family with multiple endocrine neoplasia type-1 syndrome]. / Características clínicas y moleculares de una familia con síndrome de neoplasia endocrina múltiple tipo 1.

BACKGROUND: The clinical features of multiple endocrine neoplasia type-1 (MEN-1) syndrome are hyperplasia or adenoma of the parathyroid glands, pituitary adenoma and gastroenteropancreatic endocrine tumors. This syndrome is due to mutations in the MEN1 gene, located on the q13 region of chromosome 11. Prognosis depends on tumoral growth and metastatic potential. PATIENTS AND METHOD: We reviewed the medical records of the members of a family (6 men and 2 women) with MEN-1 syndrome diagnosed between 1995 and 2007 in Hospital Donostia, San Sebastian (Spain). Familial study of all patients and family members (19 cases from 2 generations) was performed in 2 phases. The first phase consisted of mutation screening and the second of multiplex ligation-dependent probe amplification (MLPA) to detect deletions. RESULTS: Screening of mutations identified no pathogenic variants in the proband of this family. MLPA revealed a deletion affecting exons 1 and 2 of the MEN1 gene. Of the 10 family members with this molecular alteration, 8 had at least one phenotypic feature of this syndrome (hyperparathyroidism in 8, prolactinomas in 2, and gastrinomas in 3) after 12 years of follow-up. CONCLUSION: We discuss the clinical forms of MEN-1 syndrome in this family and the molecular alteration found. Study of MEN1 gene deletions should be incorporated into routine molecular screening.

[Nodular lymphoid hyperplasia of the liver. Pseudolymphoma]. / Hiperplasia nodular reactiva linfoidea hepática. Seudolinfoma.

UNLABELLED: We present a rare pathological entity of the liver and review the literature. CASE REPORT: a 33-year-old asymptomatic woman showed a space-occupying lesion on liver segment VI, which was detected incidentally on ultrasound examination performed for a gynecological disorder. Computed tomography and magnetic resonance imaging of the liver confirmed a 3-cm lesion in segment VI. Segmentectomy of segment VI was performed. Pathological diagnosis was nodular lymphoid hyperplasia of the liver. Nodular lymphoid hyperplasia or pseudo-lymphoma is a highly uncommon disease that usually develops in cirrhotic liver. Our patient was free of liver disease.

Hiperplasia nodular reactiva linfoidea hepática. Seudolinfoma / Nodular lymphoid hyperplasia of the liver. Pseudolymphoma

Presentamos una entidad anatomopatológica rara y la revisión de la literatura relacionada con ella. Caso clínico: mujer de 33 años que presenta lesión ocupante de espacio en segmento VI hepático. Hallazgo casual por ecografía realizada por trastorno ginecológico. Diagnóstico por tomografía computarizada-resonancia magnética hepática: masa hepática de 3 cm en segmento VI, por lo que se realizó segmentectomía del VI. Informe anatomopatológico: hiperplasia nodular linfoidea hepática. La hiperplasia nodular linfoide o seudolinfoma es una entidad anatomopatológica de escasa frecuencia y que nace habitualmente en hígado cirrótico. En nuestro caso, la paciente no presentaba hepatopatía crónica ni cirrosis (AU)

We present a rare pathological entity of the liver and review the literature. Case report: a 33-year-old asymptomatic woman showed a space-occupying lesion on liver segment VI, which was detected incidentally on ultrasound examination performed for a gynecological disorder. Computed tomography and magnetic resonance imaging of the liver confirmed a 3-cm lesion in segment VI. Segmentectomy of segment VI was performed. Pathological diagnosis was nodular lymphoid hyperplasia of the liver. Nodular lymphoid hyperplasia or pseudo-lymphoma is a highly uncommon disease that usually develops in cirrhotic liver. Our patient was free of liver disease (AU)

Carcinoide biliar intrahepático / Carcinoid tumor of the intrahepatic biliary tract

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Fístula pancreaticopleural: pruebas diagnósticas y tratamiento / Pancreaticopleural fistula: diagnostic tests and treatment

La fístula pancreaticopleural es una rara entidad que se da en pacientes con historia de pancreatitis crónica. A propósito de un caso en un varón de 40 años en nuestro hospital, hemos realizado una revisión de la bibliografía y hemos encontrado poco más de un centenar de casos descritos en 40 publicaciones. De ellas se concluye que la presentación es atípica, que el síntoma inicial es la disnea y que el diagnóstico se realiza mediante pancreatografía por resonancia magnética, dejando la colangiopancreatografía retrógrada endoscópica para los casos dudosos o con fines terapéuticos. El tratamiento inicialmente es médico y consiste en nutrición parenteral potal y somatostatina o análogos. Si la fístula recidiva o persiste, hay diferentes opciones como la cirugía, la colocación de un stent transpapilar o sonda nasopancreática. Globalmente, la mortalidad de la fístula pleuropancreática es del 5% (AU)

Pancreaticopleural fistula is an uncommon clinical entity that appears in patients with a history of chronic pancreatitis. Apropos of the case of a 40-year-old man in our hospital, we reviewed the literature and found 40 publications with little more than 100 patients. All of these publications highlight the atypical presentation with dyspnea as the first symptom and stress that diagnosis is based on magnetic resonance pancreatography. Endoscopic retrograde cholangiopancreatography is used in confusing cases and in planning the optimal surgical approach. Initial treatment should consist of conservative medical therapy, including total parenteral nutrition and somatostatin or its analogues. If the fistula persists or recurs, various options are available such as surgery, placement of a transpapillary pancreatic stent or nasopancreatic tube. The overall mortality rate from pancreaticopleural fistula is approximately 5% (AU)

[Pancreaticopleural fistula: diagnostic tests and treatment]. / Fístula pancreaticopleural: pruebas diagnósticas y tratamiento.

Pancreaticopleural fistula is an uncommon clinical entity that appears in patients with a history of chronic pancreatitis. Apropos of the case of a 40-year-old man in our hospital, we reviewed the literature and found 40 publications with little more than 100 patients. All of these publications highlight the atypical presentation with dyspnea as the first symptom and stress that diagnosis is based on magnetic resonance pancreatography. Endoscopic retrograde cholangiopancreatography is used in confusing cases and in planning the optimal surgical approach. Initial treatment should consist of conservative medical therapy, including total parenteral nutrition and somatostatin or its analogues. If the fistula persists or recurs, various options are available such as surgery, placement of a transpapillary pancreatic stent or nasopancreatic tube. The overall mortality rate from pancreaticopleural fistula is approximately 5%.