The second Mexican consensus on hepatocellular carcinoma. Part II: Treatment.

Hepatocellular carcinoma (HCC) is more frequently manifesting as one of the main complications of cirrhosis of the liver, its principal risk factor. There have been modifications in its incidence over the past decade, related to an epidemiologic transition in the etiology of cirrhosis, with a decrease in the prevalence of hepatitis C and an increase in nonalcoholic fatty liver disease (NAFLD) as a cause, as well as the development of HCC in the non-cirrhotic liver due to NAFLD. Genetic markers associated with the disease have been identified, and surveillance and diagnosis have improved. Regarding treatment, surgical techniques, in both resection and transplantation, have advanced and radiologic techniques, at the curative stage of the disease, have enhanced survival in those patients. And finally, there have been radical changes in the systemic approach, with much more optimistic expectations, when compared with the options available a decade ago. Therefore, the Asociación Mexicana de Hepatología decided to carry out the Second Mexican Consensus on Hepatocellular Carcinoma, which is an updated review of the available national and international evidence on the epidemiology, risk factors, surveillance, diagnosis, and treatment of the disease, to offer the Mexican physician current information on the different topics regarding hepatocellular carcinoma. In this second part of the document, the topics related to the treatment of HCC are presented.

The second Mexican consensus on hepatocellular carcinoma. Part I: Epidemiology and diagnosis.

Hepatocellular carcinoma (HCC) is more frequently manifesting as one of the main complications of cirrhosis of the liver, its principal risk factor. There have been modifications in its incidence over the past decade, related to an epidemiologic transition in the etiology of cirrhosis, with a decrease in the prevalence of hepatitis C and an increase in nonalcoholic fatty liver disease (NAFLD) as a cause, as well as the development of HCC in the non-cirrhotic liver due to NAFLD. Genetic markers associated with the disease have been identified, and surveillance and diagnosis have improved. Regarding treatment, surgical techniques, in both resection and transplantation, have advanced and radiologic techniques, at the curative stage of the disease, have enhanced survival in those patients. And finally, there have been radical changes in the systemic approach, with much more optimistic expectations, when compared with the options available a decade ago. Therefore, the Asociación Mexicana de Hepatología decided to carry out the Second Mexican Consensus on Hepatocellular Carcinoma, which is an updated review of the available national and international evidence on the epidemiology, risk factors, surveillance, diagnosis, and treatment of the disease, to offer the Mexican physician current information on the different topics regarding hepatocellular carcinoma. In this first part of the document, the topics related to epidemiology and diagnosis are presented.

Helicobacter pylori eradication in Mexico with a levofloxacin-based scheme versus standard triple therapy: Results from an open-label, randomized, noninferiority phase iiib trial. / Erradicación de Helicobacter pylori en México con un esquema basado en levofloxacina versus la triple terapia estándar: resultados de un estudio clínico de fase iiib, abierto, aleatorizado, de no inferioridad.

INTRODUCTION AND AIMS: Helicobacter pylori (H. pylori) infection remains the leading cause of several gastroduodenal diseases. Despite the fact that multiple antibiotic regimens have been used to change its associated morbidity and mortality, the prevalence of this bacterial infection continues to be disproportionately high worldwide, mainly due to antibiotic resistance. To assess the noninferiority efficacy and safety of 210-day triple regimens on H. pylori eradication, we evaluated clarithromycin 500mg, lansoprazole 30mg, and amoxicillin 1g, all bid (standard triple therapy or CLA, Group 1) vs. pantoprazole 80mg, levofloxacin 500mg and azithromycin 500mg, all od (PLA, Group 2). Both regimens were compared in treatment-naïve patients. MATERIALS AND METHODS: An open label phase IIIb randomized and noninferiority trial comparing CLA vs. PLA was carried out for a 10-day period, within the time frame of June 2012 and March 2014. Eradication was verified with 13C-urea breath testing. Gastric biopsies were tested for fluorescence in situ hybridization (FISH)-clarithromycin resistance prior to any antibiotic administration. Efficacy and safety results were analyzed according to the noninferiority methodological approach. RESULTS: From the 227 H. pylori positive subjects that were randomized, 194 were finally analyzed as per-protocol. The group 2 eradication rate was 63% and was noninferior to the group 1 eradication rate of 58.5% (upper limit 95% CI: 0.11608; below the noninferiority margin: 0.1200). FISH clarithromycin-resistance was found in 28.2% of the cases. Adverse events, all minor and self-limited, were significantly higher in group 1 than in group 2 (86 vs. 65.4%; p=0.001). CONCLUSIONS: First-line H. pylori eradication with pantoprazole/levofloxacin/azithromycin combination therapy is as effective as the standard triple therapy, with better tolerability and easier dosing. Clarithromycin resistance should be considered when selecting antibiotics in Helicobacter pylori eradication treatments. ClinicalTrials.gov identifier NCT02726269.

Utilidad de cortes seriados en biopsias prostáticas / Utility of Seriated Sections in Prostate Biopsies

Introducción: Con el empleo rutinario del antígeno prostático específico se detectan con mayor frecuencia carcinomas focales y proliferaciones atípicas de acinos pequeños (ASAP, atypical small acinar proliferation [sigla en inglés]). El número de cortes por cilindro que debe practicarse para detectar la mayoría de ellos se desconoce. Métodos: Revisamos 250 biopsias prostáticas por sextantes en el periodo 2008-2011. El promedio de cilindros por biopsia fue de 14. En cada caso se practicaron además del corte original, con 3 niveles histológicos, otros 3 cortes con 3 niveles (total: 12 niveles). En las biopsias con lesiones focales se practicó estudio inmunohistoquímico. La frecuencia de lesiones focales se comparó con un estudio previo de 1.000 biopsias donde se realizó un solo corte con tres niveles histológicos. Se anotaron los datos clínicos y de laboratorio. Resultados: Hubo 16 lesiones focales (6,4%); 7 (2,8%) correspondieron a carcinomas focales y 9 (3,6%) a proliferaciones atípicas. En el estudio previo se encontraron 13 (1,3%) carcinomas focales y 29 (2,9%) casos con proliferaciones atípicas. Conclusiones: Hubo un aumento del 4,2 al 6,4% de lesiones focales y un incremento de carcinomas del 1,3 al 2,8%. Aunque realizar cortes adicionales rutinariamente tiene inconvenientes prácticos, podría realizarse en pacientes con alta sospecha clínica de carcinoma (en particular jóvenes) o en los que existan antecedentes de proliferaciones glandulares atípicas compatibles con carcinoma (AU)

Introduction: With the routine use of prostate specific antigen, focal carcinomas and atypical small acini proliferation (ASAP) are currently detected more frequently. The number of sections per cylinder needed to detect most of them is still unknown. Methods: We reviewed 250 sextant prostate biopsies in the 2008-2011 period. The average number of cylinders per biopsy was 14. In each case, in addition to the original sections with three histological levels, three more sections were performed with three levels (total: 12 levels). Biopsies with focal lesion were analyzed immunohistochemically. The frequency of focal lesions was compared to a previous study of 1000 biopsies in which a single section was made with three histological levels. The main clinical and laboratory data were recorded. Results: There were 16 focal lesions (6.4%). Seven (2.8%) corresponded to focal carcinomas and nine (3.6%) to atypical proliferation. In the previous study, thirteen (1.3%) focal carcinomas and 29 (2.9%) cases with atypical proliferation were found. Conclusions: There was an increase of 4.2% to 6.4% of focal lesions carcinomas increased from 1.3% to 2.8%. Making additional sections in all biopsies may have practical drawbacks. However, they could be performed in patients with high clinical suspicion of carcinoma (especially in young patients), or when there is a history of atypical glandular proliferations consistent with carcinoma in previous biopsies (AU)

[Utility of seriated sections in prostate biopsies]. / Utilidad de cortes seriados en biopsias prostáticas.

INTRODUCTION: With the routine use of prostate specific antigen, focal carcinomas and atypical small acini proliferation (ASAP) are currently detected more frequently. The number of sections per cylinder needed to detect most of them is still unknown. METHODS: We reviewed 250 sextant prostate biopsies in the 2008-2011 period. The average number of cylinders per biopsy was 14. In each case, in addition to the original sections with three histological levels, three more sections were performed with three levels (total: 12 levels). Biopsies with focal lesion were analyzed immunohistochemically. The frequency of focal lesions was compared to a previous study of 1000 biopsies in which a single section was made with three histological levels. The main clinical and laboratory data were recorded. RESULTS: There were 16 focal lesions (6.4%). Seven (2.8%) corresponded to focal carcinomas and nine (3.6%) to atypical proliferation. In the previous study, thirteen (1.3%) focal carcinomas and 29 (2.9%) cases with atypical proliferation were found. CONCLUSIONS: There was an increase of 4.2% to 6.4% of focal lesions carcinomas increased from 1.3% to 2.8%. Making additional sections in all biopsies may have practical drawbacks. However, they could be performed in patients with high clinical suspicion of carcinoma (especially in young patients), or when there is a history of atypical glandular proliferations consistent with carcinoma in previous biopsies.

[Pseudohyperplastic carcinoma with xanthomatous changes: a neoplasm mimicking glandular hyperplasia of the prostate]. / Carcinoma pseudohiperplásico con cambios xantomatosos: una neoplasia que semeja hiperplasia glandular de la próstata.

INTRODUCTION AND OBJECTIVES: Varieties of prostatic adenocarcinoma whose architectural and cytological appearance mimicked benign lesions have been reported in recent decades. Such neoplasms include xanthomatous (foamy) carcinoma and pseudohyperplastic carcinoma. We recently studied five carcinomas showing a cytoarchitectural combination of both neoplasms which were confused with benign glandular proliferations. METHODS: Five cases (1.8%) of pseudohyperplastic carcinoma showing xanthomatous changes were selected from a total of 280 biopsies showing prostate carcinoma. Glandular prostatic hyperplasia was originally diagnosed in four of such cases. RESULTS: Patient age ranged from 54 and 78 years (mean, 64 years). All patients had high prostate-specific antigen levels, and digital rectal examination showed abnormalities in four of them. Neoplasms showed minimal atypia and consisted of mid- to large-sized glands arranged in nests resembling hyperplastic nodules. Glands showed papillary projections, infoldings, and undulations. Most nuclei were basal, small and hyperchromatic, and nucleomegaly was only seen in two biopsies in isolated histological fields. Several useful criteria for diagnosis of acinar carcinoma, such as perineural infiltration, mitosis, crystalloids, blue secretions, and prostatic intraepithelial neoplasm, were absent. CONCLUSIONS: Prostatic carcinoma with a pseudohyperplastic pattern and xanthomatous changes mimics hyperplastic glands. Timely detection is critical to avoid treatment delay.

Carcinoma pseudohiperplásico con cambios xantomatosos: una neoplasia que semeja hiperplasia glandular de la próstata / Pseudohyperplastic carcinoma with xanthomatous changes: A neoplasm mimicking glandular hyperplasia of the prostate

Introducción y objetivos: En las últimas décadas se han descrito variedades de adenocarcinoma prostático que por su arquitectura y su aspecto citológico semejan lesiones benignas. Estas neoplasias incluyen al carcinoma xantomatoso (espumoso) y al carcinoma pseudohiperplásico. Recientemente hemos estudiado cinco carcinomas que mostraron una combinación citoarquitectónica de ambas neoplasias y fueron confundidas con proliferaciones glandulares benignas. Métodos: De un total de 280 biopsias con carcinoma prostático se seleccionaron cinco casos (1,8%) de carcinoma pseudohiperplásico que mostraron cambios xantomatosos. Cuatro de ellos fueron diagnosticados originalmente como hiperplasia glandular prostática. Resultados: La edad de los pacientes varió de 54 a 78 años (promedio: 64 años). El antígeno prostático estuvo elevado en todos, y en el examen digital rectal se encontraron alteraciones en cuatro. Las neoplasias mostraron atipia mínima y estuvieron constituidas por glándulas de mediano y gran tamaño que se disponían en nidos semejantes a nódulos hiperplásicos. Las glándulas mostraron proyecciones papilares, plegamientos y ondulaciones. La mayoría de los núcleos fueron basales, pequeños e hipercromáticos, y sólo ocasionalmente se observó nucleomegalia. Varios criterios útiles en el diagnóstico de carcinoma acinar, incluyendo infiltración perineural, mitosis, cristaloides, secreciones azules y neoplasia intraepitelial prostática, estuvieron ausentes. Conclusiones: Los carcinomas prostáticos con patrón pseudohiperplásico y cambios xantomatosos semejan glándulas hiperplásicas. Su reconocimiento oportuno es crucial para evitar retardo en el tratamiento (AU)

Introduction and objectives: Varieties of prostatic adenocarcinoma whose architectural and cytological appearance mimicked benign lesions have been reported in recent decades. Such neoplasms include xanthomatous (foamy) carcinoma and pseudohyperplastic carcinoma. We recently studied five carcinomas showing a cytoarchitectural combination of both neoplasms which were confused with benign glandular proliferations. Methods: Five cases (1.8%) of pseudohyperplastic carcinoma showing xanthomatous changes were selected from a total of 280 biopsies showing prostate carcinoma. Glandular prostatic hyperplasia was originally diagnosed in four of such cases. Results: Patient age ranged from 54 and 78 years (mean, 64 years). All patients had high prostate-specific antigen levels, and digital rectal examination showed abnormalities in four of them. Neoplasms showed minimal atypia and consisted of mid- to large-sized glands arranged in nests resembling hyperplastic nodules. Glands showed papillary projections, infoldings, and undulations. Most nuclei were basal, small and hyperchromatic, and nucleomegaly was only seen in two biopsies in isolated histological fields. Several useful criteria for diagnosis of acinar carcinoma, such as perineural infiltration, mitosis, crystalloids, blue secretions, and prostatic intraepithelial neoplasm, were absent. Conclusions: Prostatic carcinoma with a pseudohyperplastic pattern and xanthomatous changes mimics hyperplastic glands. Timely detection is critical to avoid treatment delay (AU)

Carcinoid tumors of the duodenum and ampulla of vater: a clinicomorphologic, immunohistochemical, and cell kinetic comparison.

Carcinoid tumors of the ampulla of Vater (ACs) differ from duodenal carcinoid tumors (DCs). A search for AC and DC was made between 1980 and 2000. The clinicopathologic features and follow-up were assessed. Immunohistochemistry for panneuroendocrine markers, hormone products, proliferating cell nuclear antigen (PCNA), Ki- 67, p21(cip1), and p27(kip1) were performed. A blind proliferative index counting 500 cells was made. Differences were contrasted using the Fisher exact and 2-sided Student t test. Five ACs and 8 DCs were identified in 9 women and 4 men with median ages of 59 and 64 years and mean tumor diameters of 1.6 and 1.85 cm, respectively. All patients with AC presented jaundice, and most patients with DC were asymptomatic (P = .047). Metastases were present in 4 ACs and 1 DC (P =.03). Tumor cells expressed synaptophysin and chromogranin in 60% of ACs and in 100% and 87% of DCs. Gastrin was expressed in 75% of DCs and 20% of ACs (P < .05). The mean value for PCNA index was 4.0% in ACs and 3.2% in DCs, and mean values for Ki-67 were 12.2% and 10.2%, respectively (P = NS). Expression of p21(cip1) and p27(kip1) was observed in 40% of ACs and 37.5% and 12.5% of DCs. Three of 5 patients with AC died of the disease within an average of 11 months, and none of the patients with DC had died at 103 months of follow-up. The more aggressive behavior of ACs is not associated with higher proliferative indices or with different expression of cell cycle inhibitors.

Sporadic type composite pheochromocytoma with neuroblastoma: clinicomorphologic, DNA content and ret gene analysis.

Composite pheochromocytomas (CP) account for only 3% of all pheochromocytomas. We analyzed the clinical, immunohistochemical, ultrastructural, DNA content, and 634 ret mutation features in a 56-year-old Mexican woman with CP localized in the right adrenal gland and associated to a blood pressure of 140/90 mmHg. Clinical symptoms were absent after surgery. The tumor showed pheochromocytoma and neuroblastoma components. This dual phenotype was supported by light microscopy and corroborated by immunohistochemistry and ultrastructural findings. Flow cytometric analysis showed that both components were diploid. A genetic mutational analysis of the ret oncogene in exon 11 showed no 634 mutation. This case demonstrates the indolent behavior of neuroblastoma associated to a sporadic-type CP in an adult patient.

Histologic diagnosis of primary hyperparathyroidism: a concordance analysis between three pathologists.

Primary hyperparathyroidism (HPT) is caused by a parathyroid adenoma, hyperplasia or carcinoma. Difficulties for the histologic diagnosis of abnormal parathyroid tissue are widely recognized. The aim of the study was to evaluate the reproducibility of the morphologic criteria through a concordance study among three pathologists. Representative slides of 40 patients with biochemically primary HPT stained with hematoxylin and eosin were blindly reviewed by three pathologists. Each pathologist established the diagnosis of adenoma or hyperplasia and assessed the presence of fat cells, a rim of normal tissue, a fibrous capsule, the number of cellular types, the lobular pattern, and the characteristics of the blood vessel's wall. A concordance analysis was then performed. Mean age of the group was 55 +/- 14 yr, 7 were males and 33 females. The concordance analysis among the three pathologists for the differential diagnosis between adenoma and hyperplasia, showed a Kappa index of 0.5. Kappa index for the presence of fat cells was 0.56, for the presence of a rim of normal tissue 0.47, and for the number of cellular types 0.29. The concordance for the differential diagnosis between parathyroid adenoma and hyperplasia in this study was low.

[Neutropenic enteropathy associated with autoimmune diseases. A more aggressive presentation]. / Enteropatía neutropénica asociada a enfermedades autoinmunes. Una presentación más agresiva.

BACKGROUND: There is just one case report dealing with neutropenic enteropathy associated with autoimmune diseases. METHOD: An autopsy analysis of neutropenic enteropathy in autoimmune and hematologic diseases was carried on. Gross findings and slides were reviewed. A blind analysis is of the mucosal lesions in small and large intestine as well as of the clinical course was made. RESULTS: Seventeen cases of neutropenic enteropathy were found a once period of 13 years (1,068 autopsies). Fourteen cases were seen in patients with hematologic diseases and three in patients with autoimmune diseases. Acute symptoms had a 6-day evolution and were characterized by abdominal pain, diarrhea, ascitis, and fever in autoimmune diseases. Extension of colonic damage was 58 and 13% in small bowel. Cases associated with hematologic diseases had longer clinical course with fever abdominal pain and colonic lesions in 21% of the surface and small bowel lesions in 6% of the mucosa. No acute inflammatory infiltrate around the necrotic zones was observed in either group Azathioprine, steroids, methotrexate, and alkylating agents were associated to neutropenia. CONCLUSIONS: Clinical evolution and morphologic findings were more severe in neutropenic enteropathy associated with autoimmune diseases than in patients with hematologic diseases.

[Primary lipoma of the liver]. / Lipoma primario de hígado.

A case of lipoma of the liver is reported in a 57-year-old woman with a 10-month history of non-insulin dependent diabetes mellitus and 3 days with abdominal pain, distention, nausea, and vomiting. On medical examination, the liver was palpable 5 cm below the right costal margin without splenomegaly or ascites. A CT scan revealed a well-defined fat attenuation tumor and an MR demonstrated a well-circumscribed lesion with bright signal intensity. An extended right hepatic lobectomy was performed. The resected specimen measured 28.6 x 18.3 x 8.2 cm and weighed 2,200 g. The yellow and well-circumscribed tumor measured 15 x 9.5 cm and was composed of mature adipose cells pushing the liver tissue at the periphery. The patient was asymptomatic 6 months after surgery.