[Effectiveness of second-generation direct-acting antivirals in chronic hepatitis C]. / Efectividad de los antivirales de acción directa de segunda generación en el tratamiento de la hepatitis C crónica.

BACKGROUND: Second-generation direct-acting antivirals (DAA) have shown high sustained virologic response (SVR) for the treatment of chronic hepatitis C in clinical trials. The objective of this study is to estimate DAA effectiveness in treatment of this disease. METHODS: Hepatitis C virus (HCV) monoinfected patients and HCV-human immunodeficiency virus (HIV) coinfected pa-tients who started interferon-free DAA based regimens during 2015 were included. The primary effectiveness outcome was SVR, defined as an undetectable viral load 12 weeks after the end of treatment. RESULTS: A total of 293 patients were enrolled, and 52 (17.7%) were HIV coinfected. HCV 1b genotype was the most prevalent in monoinfected patients (41.5%) and 1a in HIV coinfected patients (40.4%). The proportion of cirrhosis was higher among HIV coinfected patients (69.2% vs 41.1%; p<0.0001), mostly Child-Pugh A. SVR was achieved by 96.9% of patients (284/293), in an intention-to-treat analysis (CI 95%: 94.9-98.9), in which just 4 people had virologic failure. Both naïve and pretreated patients had SVR higher than 95%, and in most of subgroups, according to the presence of cirrhosis, HIV coinfection and HVC genotype, effectiveness rates were near or above 90%. CONCLUSIONS: DAA are highly effective, with similar or higher rates of SVR than that found in clinical trials, and even among difficult to treat populations.

[Relation between preoperative prognostic Onodera's Index and postsurgery complications in the R0 gastric carcinoma resection]. / Relación entre el índice de Onodera pre-operatorio y las complicaciones post-cirugía R0 en el cáncer de estómago.

BACKGROUND: It has been postulated in the Asian literature that a low prognostic nutritional index (OI) could be associated with a higher rate of complications following radical gastric cancer surgery, but there is a lack of data concerning western countries. The aim is to analyze the relationship between a low preoperative OI and the frequency and severity of surgical complications in R0 gastric cancer resection. PATIENTS AND METHODS: In the present article, 124 cases of gastric cancer with R0 resection were reviewed. An OI <45 was considered pathologically low. The complication rate was compared between both groups: OI <45 vs OI =45. A multivariate analysis was performed adjusting for: age > 68 years, ASA score, preoperative hemoglobin level <12 g/dL, pTNM stage, administration of neoadyuvant therapy and type of gastrectomy. The relationship between a PNI<45 and the severity of complications graded according to the Clavien-Dindo classification was determined. RESULTS: We registered mild complications in 11.3% of cases, severe complications in 9.7% and a mortality rate of 2.4%. Patients with a OI <45 showed a higher complication rate: 37.7% versus 12.7% [odds ratio (OR) = 4.17; CI95% = (1.71 - 10.20 p = 0.001)], confirmed by multivariate analysis: [OR = 4.17; CI95% = (1.54 - 11.30); p = 0.005]. Patients with OI <45 had more severe complication-exitus: 20.8% versus 5.6% [OR = 4.39; CI95% = (1.31 - 14.68); p = 0.011]. CONCLUSIONS: We confirmed that patients with a low preoperative OI show a higher independent risk of complications after a R0 gastric cancer resection in a western country as well. Complications, in these cases with OI <45, registered a significantly higher severity grade.

[Predictive pre-treatment value of the Prognostic Nutritional Index on survival in gastric carcinoma]. / Valor predictivo pre-tratamiento del Índice Pronóstico Nutricional sobre la supervivencia del carcinoma gástrico.

BACKGROUND: The Prognostic Nutritional Index (PNI) combines the values of circulating lymphocytes and serum albumin and, in the Asian literature; it has been related with the prognosis following R0 resection of gastric cancer. No results are available in Western countries. We study the possible independent prognostic value, at the moment of the tumour's diagnosis, of PNI on survival. PATIENTS AND METHODS: We review 234 consecutive gastric carcinomas, calculating global survival and tumour-specific survival. We considered pre-treatment PNI values of < 40 to be pathological. We carried out a univariate and multivariate analysis of cases of survival according to PNI, including the following adjustment variables: age > 70 years, ASA anaesthetic at the time of diagnosis, size of the neoplasia > 5cm, macroscopic type, undifferentiated degree and TNM clinical stage through echoendoscopy and/or CAT. RESULTS: The univariate analysis registered greater global and specific survival in cases with PNI ≥ 40 versus PNI < 40: [HR = 2.28; CI 95% = (1.60-3.26); p< 0.001] and [HR = 2.35; CI 95% = (1.63-3.39); p< 0.001], respectively. The multivariate analysis confirmed a better independent prognosis in cases with OI ≥ 40: global survival: [HR = 1.48; CI 95% = (1.02-2.16); p = 0.040], specific survival: [HR = 1.51; CI 95% = (1.03-2.23); p = 0.036]. CONCLUSIONS: At the moment of diagnosis of gastric cancer and including all registered cases, a PNI ≥ 40 is accompanied by a signifi-cantly greater global and tumour-specific survival. In our series, this better prognosis is independent of the patient's age group, his/her ASA classification, the size and degree of differentiation of the neoplasia and its TNM clinical stage.

[Prognostic value of Onodera's index in colorectal cancer survival]. / Valor pronóstico del índice de Onodera en la supervivencia del cáncer colorrectal.

BACKGROUND: Onodera's prognostic nutritional index (OPNI), which is calculated using total lymphocyte count and serum albumin level, has been used as a marker of nutritional status, with its potential prognostic value in colorectal cancer having recently been postulated in Japan and China. There is still no data on the predictive value of OPNI in a Western population. PATIENTS AND METHODS: A consecutive case series of 207 patients scheduled for colorectal cancer resection with curative intent was reviewed. Pre-treatment OPNI was calculated using the formula: [10 x serum albumin (g/dl) + 0.005 x lymphocytes/mm²]. OPNI values under 40 were considered low. Univariate and multivariate analysis were performed on survival curves, comparing cases with OPNI values less than, equal to or greater than 40 (Cox model, stepwise), in the overall series and in pTNM stage II. RESULTS: The median for clinical follow-up was 81 months (interquartile range 60-96). Twenty-six patients (12.6%) had a low OPNI (≤ 40). In the multivariate analysis, patients with low OPNI showed less favourable survival curves, both in the overall series: [p <0.001; HR = 3.16; 95% CI = 1.67-5.94] and in the 78 cases in pTNM stage II: [p <0.004; HR = 4.36; 95% CI = 1.61-11.76]. CONCLUSIONS: A low pre-treatment OPNI (<40) has an independent, unfavourable predictive value on survival in European patients with resected colorectal cancer, both in the overall series and in pTNM stage II.

Endoscopic localization of colorectal cancer: study of its accuracy and possible error factors.

INTRODUCTION: accurate preoperative localization of colorectal cancer (CRC) is very important, with a wide range of published error rates. AIMS: to determine accuracy of endoscopic localization of CRC in comparison with preoperative computed tomography (CT). To analyse variables that could be associated with a wrong endoscopic localization. PATIENTS AND METHODS: endoscopic and CT localization of a series of CRC without previous surgery were reviewed. We studied the concordance between endoscopic and radiologic localization against operative findings comparing accuracy of endoscopy and CT. We analysed the frequency of wrong endoscopic diagnoses with regard to a series of patient, endoscopy and tumor variables. RESULTS: two hundred thirty seven CRC in 223 patients were studied. Concordance with surgical localization was: colonoscopy = 0.87 and CT = 0.69. Endoscopic localization accuracy was:91.1%; CT: 76.2%: p = 0.00001; OR = 3.22 (1.82-5.72). Obstructive cancer presented a higher rate of wrong localization: 18 vs. 5.7% in non-obstructive tumors (p = 0.0034; OR = 3.65 (1.35-9.96). Endoscopic localization mistakes varied depending on tumor location, being more frequent in descending colon: 36.3%, p = 0.014; OR = 6.23 (1.38-26.87) and cecum: 23.1%, p = 0.007; OR = 3.92 (1.20-12.43). CONCLUSIONS: endoscopic accuracy for CRC localization was very high and significantly better than CT accuracy. Obstructive tumor and those located in the descending colon or cecum wereassociated with a significant increase of the error risk of CRC endoscopic localization.

[Tissue expression of mismatch repair proteins and tumor lymphocytic infiltration: prognostic significance in resected colorectal carcinoma]. / Expresión tisular de proteínas reparadoras e infiltración linfocítica tumoral: significado pronóstico en el carcinoma colorrectal resecado.

BACKGROUND: In colorectal cancer there is discussion about the possible relation between the mismatch repair protein expression (MMRPE) and tumour lymphocytic infiltration (TLI), as well as the possible prognostic effect of both factors. METHODS: A review was made of 243 colorectal cancers, consecutively resected. We made an immunohystochemical study of the MMRPE of MLH1, MSH2 and MSH6. The TLI was evaluated through CD3 staining in the tumoural epithelium. We compared mortality and post-operative tumoural progression amongst the cases with and without MMRPE and with and without TLI. Additionally, we studied mortality and tumoural progression amongst MMRPE (+) cases, according to whether or not they presented TLI. RESULTS: Thirteen point six percent of the tumours expressed MMRPE (+) and 25.5% TLI (+). The follow-up was: 73.8±34.6 months. The frequency of TLI (+) turned out to be similar between MMRPE (+) tumours: 27.3% and MMRPE (-): 25.2% (p = 0.80). The MMRPE (+) cases showed less mortality: 12.1% versus 23.3% (p = 0.15) and less tumoural progression: 21.2% versus 29% (p = 0.35). The ITL neoplasias (+) had a lower mortality: 9.7% versus 26% [p = 0.007; OR = 3.27(1.25-9.05)] and tumoural progression: 12.9% versus 33.1% [p = 0.002; OR = 3.35 (1.42-8.15)]. The 9 MMRPE (+) and ILT (+) tumours did not present mortality or tumoural progression, against a mortality: 16.7% and progression: 29.2% of the 24 MMRPE (+) and TLI (-) cases p = 0.19 and p = 0.07 respectively. CONCLUSIONS: No relation was found between MMRPE and TLI, with very similar rates of TLI (+) between cases with and without MMRPE. The LTI (+) showed a favourable prognostic effect higher than that of the MMRPE (+). The combination of LTI (+) and MMRPE (+) seems to have an accumulative protective effect, although its limited frequency reduces the significance of the finding.

[Incidence and characteristics of eosinophilic esophagitis in adults]. / Incidencia y características de la esofagitis eosinofílica (EE) en adultos.

Eosinophilic esophagitis (EE) is a disease characterised by the infiltration of esophageal mucous by eosinophils, whose incidence in adults seems to have been increasing in recent years, in a way that is similar to what is occurring with other diseases of a probable immunoallergic aetiology. It predominates in young adults and is mainly expressed by dysphagia and esophageal food impactation. Treatment is based on eliminating the allergen that is potentially involved and the administration of corticoids. This article offers a retrospective review of EE cases diagnosed in the Hospital de Navarra between January 2002 and August 2008, with 25 patients found, which represents an incidence of 2.13 cases/105 inhabitants/year. Seventy-two percent of our patients showed dysphagia and 52% a history of food bolus impaction, with endoscopic alterations found in 23 of the 25 cases. Out of 24 patients studied, 76% showed an alimentary allergy or neumoallergens, which supports the immunoallergic basis of the disease and the need for an allergy exam in all patients with EE. The majority of our patients (22 out of 24 evaluated) presented a good clinical response to treatment, which was based on avoiding exposure to the potentially involved allergen and/or the administration of corticoids (topical or systemic) and/or the administration of proton pump inhibitors.

[General malaise and diarrhea as the main manifestations of Giardia lamblia infection]. / Síndrome general y diarrea como manifestación de infección por Giardia lamblia.

Giardia lamblia is a ubiquitous intestinal protozoan. Transmission, which is fecal-oral, occurs after cyst ingestion, excystation and enterocyte adhesion. Symptoms include diarrhea, abdominal pain and other less frequent manifestations such as nausea, anorexia and weight loss. Enzyme immunoassay and direct fluorescent-antibody assay for antigen detection in stool samples, and small intestine biopsy provide the best diagnostic sensitivity. When an infection is suspected, duodenal biopsy should be carried out, even though endoscopic appearance may be normal. The most effective drugs in the treatment of this infection are metronidazole and tinidazole. We report a case of G. lamblia infection. The patient reported a clinical history of 4 months' duration with general malaise and diarrhea for the previous month. This form of presentation is rarely found in adults with this parasitosis. The diagnosis was based on the results of duodenal biopsy. The patient showed satisfactory response to treatment with metronidazole.

[Duodenal gangliocytic paraganglioma]. / Paraganglioma gangliocítico duodenal.

We present the case of an 85 year old male who was admitted to hospital with abdominal pain and jaundice. Different explorations were performed for this reason, with a mass observed in his 2nd duodenal portion. Histological study showed that it was a duodenal gangliocytic paraganglioma. The clinical characteristics of this infrequent tumour are described and we review the diagnosis and treatment.

[Acute hepatitis C virus infection]. / Infección aguda por el VHC.

Acute hepatitis C virus infection produces clinical and biochemical features that is non-specific and indistinguishable from those caused by other hepatotropic viruses. The specific diagnosis of acute hepatitis C virus infection is based on the detection of serum RNA-HCV through a technique of PCR whose result will be positive after 1-2 weeks of the initial contact with the virus. The anti-bodies against HCV are detected later (after 7-8 weeks on average), and are not useful, as an isolated determination, in distinguishing acute infection from chronic infection or in clearing the virus (spontaneous or following treatment). Fifty-five to eighty-five percent of patients with acute HCV infection do not clear the virus and develop a chronic infection with risk of evolution to cirrhosis and of developing hepatocellular carcinoma. For this reason, the present tendency is to treat with interferon all those patients in whom RNA-HCV remains positive after 3-4 months following diagnosis of acute infection

[Chronic hepatitis C virus infection]. / Infección crónica por el VHC.

Following acute hepatitis C virus infection (HCV), a significant percentage of patients do not clear the virus and develop a chronic hepatitis C. The symptoms, when they exist, are usually unspecific. Besides, approximately one third of the patients present extrahepatic manifestations of the infection, basically due to the lymphotropism of HCV. Outstanding amongst these, due to their clear association with HCV, are mixed cryoglobulinaemia and the production of autoantibodies (autoAb). Other diseases such as non-Hodgkin lynphoma (NHL) or autoimmune thyroiditis do not have a clearly established association. Although the majority of patients with chronic hepatitis C have slight or moderately high levels and fluctuations of transaminases, as many as one third of those infected can show persistently normal levels of transaminases. The diagnosis of chronic HCV infection is based on serological tests, which detect the presence of antibodies against HCV, and on virological tests that detect RNA of the HCV, which confirm the existence of active infection. Finally, an important topic of chronic HCV infection, following diagnosis, is to ascertain the stage of fibrosis and the degree of inflammation, since both characteristics are very important for predicting the natural evolution and the need for treatment. Nowadays, this information can only be obtained through liver biopsy, which is recommended in patients with chronic HCV infection and high transaminases. Whether liver biopsy should be performed in patients with normal transaminases is still subject of controversy.

[Treatment of chronic hepatitis C virus infection]. / Tratamiento de la infección crónica por el VHC.

At present the treatment of chronic hepatitis C virus infection is based on the combination of pegylated interferon (PEG-INF) and rivabirin (RBV) and basically attempts to eradicate the viral infection (sustained viral response). The pattern depends above all on the viral genotype, hence, patients with genotype 1, 4 and 5 require 48 weeks of treatment and high doses of RBV, while those with genotype 2 and 3 require 24 weeks of treatment and low doses of RBV. All patients with chronic C infection are possible candidates for antiviral therapy. However, given that the response to treatment is variable, that the treatment has secondary effects and supposes a high economic cost, it is recommendable in patients with hypertransaminasemia and moderate-severe chronic hepatitis in the histological study, as long as there are no counter-indications. This does not exclude other groups of patients who should be evaluated individually. In those patients with compensated hepatic cirrhosis, treatment can stabilise the disease and reduce the risk of complications appearing, although the rate of response is lower and some adverse effects are more frequent. In patients who have received previous antiviral treatment with standard interferon, alone or in association with RBV, without response to this or with response but later relapse, the decision on treatment must be individual. In patients with coinfection by human immunodeficiency virus (HIV), special attention must be paid to the degree of evolution of the disease due to HCV and to HIV, as well as the possible hepatoxicity of the antiretroviral treatment and the risk of secondary effects.

Digestive anisakiasis: clinical manifestations and diagnosis according to localization.

OBJECTIVES: Digestive anisakiasis is a parasitic disease whose clinical manifestations depend on the effect of Anisakis simplex on the digestive tract wall. Larvae are acquired by eating raw or poorly cooked fish. It is estimated that this entity is currently under-diagnosed, although publications are becoming increasingly common. We analyse our series of digestive anisakiasis checking localization and studying its relationship with symptoms and method of diagnosis. PATIENTS AND METHOD: We review 23 cases of digestive anisakiasis registered between 1989 and 2001, and confirmed by the measurement of specific serum Ig E antibodies. We analyse clinical symptoms and method of diagnosis according to whether localization was gastro-duodenal or intestinal, evaluating whether surgical intervention was needed for a correct diagnosis. The statistical analysis is made using Fisher's test. RESULTS: 23 patients were included between 1989 and 2001, 8 with gastro-duodenal localization and 15 with intestinal localization. All patients with intestinal localization had abdominal pain. Symptoms were less severe for gastro-duodenal cases, and diagnosis was made by clinical suspicion and subsequent gastroscopy, whereas more than a half of intestinal cases required histological examination of a surgical specimen for correct diagnosis. In the remaining half, diagnosis was made by abdominal ultrasonography. We also observed that the need for surgery has decreased with time from 6/6 cases in the 1989-1996 period of time to 2/9 in the 1997-2001 period of time. CONCLUSIONS: Clinical manifestations of anisakiasis vary depending on localization, symptoms being more severe in intestinal forms. The diagnosis of gastro-duodenal anisakiasis did not need surgery and was based mainly on gastroscopy findings, whereas intestinal forms frequently required histological examination of the surgical specimen. In our hospital, a higher index of clinical suspicion allowed us to diagnose intestinal anisakiasis without examination of surgical specimens in the last years.

Sarcoma de Monte de Venus: una presentación infrecuente / Testicular germ-cell tumor in two siblings: a propos of a new case

Los sarcomas de partes blandas son raros. Tan sólo representan el 0,7 por ciento de los tumores malignos en el adulto, y el 1-3 por ciento de los tumores de vulva. Embriológicamente derivan del mesenquima primitivo y pueden asentar en cualquier parte del organismo.Existe gran variedad de tipos histológicos con más de 30 subtipos, siendo difícil la distinción entre ellos.A propósito de un caso de sarcoma en el Monte de Venus tratado en nuestro servicio realizamos una revisión de la bibliografía existente (AU)

[Abdominal pain and infection by the varicella-zoster virus following bone marrow transplant]. / Dolor abdominal e infección por el virus varicela zoster tras trasplante de médula ósea.

Infection by the varicella-zoster virus (VZV) is an important cause of morbidity and mortality in patients who have received a bone marrow transplantation (BMT), both autologue and alogenic. Infection is generally produced in the first post-transplant year and, in its disseminated form, it can show itself through abdominal pain that translates the visceral affectation, pain that can precede the appearance of the characteristic cutaneous lesions by days, making diagnosis difficult. The clinical case described belongs to a patient who, 10 months after a bone marrow transplant, showed an infection by varicella-zoster virus, manifested through abdominal pain due to hepatic affectation, with an interval of 2 days between the start of pain and the appearance of cutaneous lesions. The diagnosis and treatment of these patients is discussed.

[Cost effectiveness study on the use of somatostatin for reduction of acute pancreatitis after ERCP]. / Estudio de coste-efectividad del empleo de somatostatina para la disminución de pancreatitis agudas post-CPRE.

OBJECTIVES: Recent studies show that intravenous injection of somatostatin before endoscopic retrograde cholangiopancreatography (ERCP) is associated with a significant reduction in the rate of post-ERCP acute pancreatitis. The lack of data in our environment led us to study the possible economic benefits of somatostatin administration, obtained through the reduction of costs due to post-ERCP acute pancreatitis. MATERIAL AND METHODS: Theoretical study of the direct costs of post-ERCP acute pancreatitis using Markov's tree decisions. The costs of the group pre-treated with intravenous administration of 3 mg of somatostatin were compared with those of the control group. Post-ERCP rates of pancreatitis of 10% were accepted in the control group and rates of 3% were accepted in the somatostatin group. The costs of the different types of pancreatitis were as follows: costs with and without complications and with surgical intervention were based on the diagnosis related group-weights applied by the Ministry of Health in the Contract-program of the Health Service of Navarre for 1999. A sensitivity analysis was carried out to determine the rate of post-ERCP pancreatitis from which an economic benefit would be obtained in the group pre-treated with somatostatin. RESULTS: Mean theoretical cost per procedure was 121,640 pesetas for the control group and 105,539 for the group pre-treated with somatostatin. Saving per patient was 13.26% (16,101 pesetas). The sensitivity analysis revealed that in the control group premedication produced an economic benefit starting from a pancreatitis rate of 4.2%. CONCLUSIONS: Independently of the clinical benefit signifying the reduction of post-ERCP pancreatitis, somatostatin administration led to a saving of 16,101 pesetas per patient. Accepting that the pancreatitis rate in the treated group was proportionately reduced, the sensitivity analysis showed that premedication produced an economic benefit starting from a pancreatitis rate of 4.2% in the control group.

[Upper digestive haemorrhage due to Mallory-Weiss syndrome. Role of endoscopic sclerotherapy]. / Hemorragia digestiva alta por síndrome de Mallory-Weiss. Papel de la escleroterapia endoscópica.

BACKGROUND: Although Mallory-Weiss syndrome is responsible for between 0.5 and 17% of the cases of upper digestive haemorrhage, the information existing on the endoscopic treatment of this syndrome is scarce. MATERIAL AND METHODS: We made a retrospective study of 71 patients with haemorrhage due to Mallory-Weiss syndrome, dividing them into two groups according to the treatment they had received (medical or medical-endoscopic). Hence, 60 patients (30 with clean laceration, 9 with signs of prior haemostasia and 21 with fresh clotting) had been treated with procinetics and/or antisecretories alone, while the 11 remaining (8 with active haemorrhage, 2 with visible vessel and 1 with fresh clotting) had also received endoscopic treatment with sclerotherapy. We compared the clinical and analytical characteristics and the evolution of both groups of patients, analysing the data by means of the Mann-Whitney U and the chi 2 test. RESULTS: The endoscopic sclerosis group showed maelenas more frequently and more severe analytical data of haemorrhage (p<0.01). Endoscopic sclerosis brought initial control of the haemorrhage in all the patients, with a low index of haemorrhage relapse, similar to the group receiving exclusively medical treatment. CONCLUSIONS: In our series, the patients with Mallory-Weiss syndrome with active bleeding or visible vessel presented a haemorrhage with a greater clinical and analytical repercussion. In this group of patients, endoscopic sclerotherapy controlled the haemorrhage and/or prevented rebleeding, in the absence of complications.