Paediatric interventional cardiology in Costa Rica: diagnostic reference levels and estimation of population dose.

The goal of the present study was to propose a set of national diagnostic reference levels (DRLs) in Costa Rica for paediatric interventional cardiology (IC) procedures classified by age and weight and to estimate the collective dose of the paediatric population from these intervention practices. The data collection period was May 2016 to May 2017. The third quartile of patient dose data distributions for kerma-area product (KAP) values was set as the national DRLs. A sample of 154 paediatric IC procedures (collected in the national paediatric hospital with a single x-ray system) was used and divided into four age ranges and five weight ranges. The national DRLs obtained for KAPs by age range were 1.79 Gy cm2 (<1 year) to 23.0 Gy cm2 (10-15 years). The national DRLs obtained for KAPs by weight range were 1.0 Gy cm2 (<10 kg) to 49.6 Gy cm2 (50-79 kg). The contribution to the collective dose of the population of Costa Rica amounted to 0.78 person Sv.

Analgesia in patients with acute abdominal pain.

BACKGROUND: For decades, analgesia for patients with acute abdominal pain was withheld until a definitive diagnosis was established for fear of masking the symptoms, changing physical findings or ultimately delaying diagnosis and treatment of a surgical condition. This non-evidence-based approach has been challenged by recent studies demonstrating that the use of analgesia in the initial evaluation of patients with acute abdominal pain leads to significant pain reduction without affecting diagnostic accuracy. However, early administration of analgesia to such patients can greatly reduce their pain and does not interfere with a diagnosis, which may even be facilitated due to the severity of physical symptoms being reduced. OBJECTIVES: To determine if the currently available evidence supports the use of opioid analgesia in patient management with acute abdominal pain; and to assess changes in a patient comfort while awaiting definitive diagnosis and final treatment decisions. SEARCH STRATEGY: Trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, issue 4, 2006), MEDLINE (1966 to 2006) and EMBASE (1980 to 2006). Randomized controlled trial filter for MEDLINE and EMBASE search. Trials will also be identified by "related articles". The searches were not limited by language or publication status. SELECTION CRITERIA: Randomized controlled trials (RCTs) that include adult patients with acute abdominal pain, without gender restriction, comparing any opioid analgesia regime to no analgesia administered prior to any intervention regardless of outcomes. DATA COLLECTION AND ANALYSIS: Two authors looked independently at the titles and abstracts of reports. Potentially relevant studies selected by at least one reviewer were retrieved in full text versions for potential inclusion. Allocation concealment was important to avoid bias and was graded using the Cochrane approach. The data from studies included was reviewed qualitatively and quantitatively using the Cochrane Collaborations methodology and statistical software RevMan Analysis 1.0.5. In the case of homogeneity or non- worrying heterogeneity, a random effects model was used. Sensitivity analysis was performed based on quality assessment. MAIN RESULTS: Six studies fulfilled the inclusion criteria. Improvement with use of opioid analgesia was verified in variables patient comfort, reduction of pain, changes in physical examination. AUTHORS' CONCLUSIONS: The review provide some evidence to support the notion that the use of opioid analgesics in patients with acute abdominal pain is helpful in terms of patient comfort and does not retard decisions to treat.

Effect of hyaluronic acid on the regulation of inflammatory mediators in osteoarthritis of the temporomandibular joint: a systematic review.

Osteoarthritis is one of the most frequent pathologies affecting the temporomandibular joint (TMJ). There is evidence that the use of intra-articular hyaluronic acid (HA) for the treatment of this disorder achieves positive effects through a reduction in inflammatory mediators. A systematic review of the available evidence regarding the regulation of inflammatory mediators when applying HA in osteoarthritis of the TMJ in humans was performed. The Web of Science, Embase, ScienceDirect, MEDLINE, Scopus, EBSCOhost, and LILACS databases, SciELO library, and search engine Trip Database were searched systematically. Two thousand eight hundred and sixty-three related articles were found, of which only two met the selection criteria (both were clinical trials and evidence level 2b for treatment studies). These two articles represented a population of 87 patients. Both articles reported that the application of HA had a positive effect on the regulation of inflammatory mediators; the mediators studied were those of the plasminogen activator system and levels of nitric oxide. The limited evidence available suggests that the application of HA regulates various inflammatory mediators in osteoarthritic processes in the TMJ. Nevertheless, further evidence in this regard is required, through the study of specific pathologies of the TMJ, complementing the assessment of clinical parameters with molecular studies, and generating good quality clinical studies with larger sample sizes.

Floating stoma: An alternative strategy in the context of damage control surgery.

INTRODUCTION: Floating stoma (FS) is a strategy to be considered in the context of damage control surgery (DCS). The purpose of this study is to describe the technique used and the results of a series of patients where FS was used. METHODS: Case series of relaparotomized patients at two emergency services in Temuco, Chile (2005-2014). In all of them, once drainage of septic focus or damage was controlled, the abdomen was left open with a Bogota bag (BB) and FS. Outcome variables were FS indications, morbidity, time to first replacement of BB, definitive maturation of the stoma (DMS), time to withdraw the BB and mortality. RESULTS: FS was performed in 46 patients with a mean age of 49.3±21.1 years; 63% were female. The indication of FS was abdominal sepsis by secondary peritonitis (69.6%), abdominal trauma (17.4%), and mesenteric ischemia (13.0%). Morbidity was 37.0%. Median time to first replacement of BB, DMS and time to withdraw the BB were 84hours, 3.5 days and 49 days, respectively. Mortality was 19.6%. CONCLUSION: FS is a temporary resource reserved for special surgical cases. It is associated with morbidity and mortality inherent with the severity of the patients on whom it can be used.

Laparoscopic pericystectomy for liver hydatid cysts.

BACKGROUND: The laparoscopic approach for managing of liver echinococcosis is a controversial issue because of scarce experience worldwide. The aim of this report is to describe the technical details of our laparoscopic method and present our results. METHODS: Consecutive cases of liver echinococcosis managed by laparoscopic surgery are reported. Thoracic x-ray and abdominal ultrasound had been performed previously. The following aspects were considered as selection criteria: unique cyst located in segments III, IV, V, VI, and VIII; diameter less than 7 cm; and no evidence of infection or calcification. An evacuating puncture was performed, germinative membrane removed, and pericystectomy performed, which extirpated the pericystic structure with the surrounding liver parenchyma. Specimens were removed in a plastic bag through one of the ports. Surgical morbidity, hospital stay, time until return to work, and evidences of hydatid recurrence were measured. RESULTS: Surgery was performed on eight patients (5 women and 3 men) with a mean age of 44.9 years (range, 22-83 years) who had a liver hydatid cyst with a mean diameter of 6.6 cm (range, 5-7 cm). During a mean follow-up period of 30 months (range, 23-44 months), no morbidity or hydatid recurrence were verified. Hospital stay was 2 days in all cases, and return to work was within 15 days. CONCLUSION: This laparoscopic technique, applied with selective criteria, can be a useful alternative for treating patients with liver hydatidosis because its results are comparable with those for open surgery studies involving similar follow-up time.

Design of a scale for measuring post-surgical complications in third molar surgery.

The aim of this study was to design a scale for measuring the extent and severity of post-surgical complications in third molar surgery. A multi-stage study using a quantitative methodology and qualitative interview strategy was employed. The degree of importance of signs and symptoms in the evaluation of post-surgical complications was initially observed using a self-report questionnaire administered to maxillofacial surgeons and surgical residents at the International Conference of Oral and Maxillofacial Surgeons in 2011. Then, using exploratory factor analysis, the items and components of the scale were established, with internal consistency determined using Cronbach's alpha. Finally, a group of experts performed a face validity analysis and provided conceptual definitions for the items and components. Thirty-six signs and symptoms were evaluated by 100 respondents, with the most relevant being 'suppuration' and 'abscess'. Factor analysis of the results identified three factors, defined as 'secondary complication', 'soft tissue infection', and 'osseous involvement' (Cronbach's alpha>0.7). Finally, a preliminary scale was designed comprised of these three components and 10 items. In this way, a preliminary scale for measuring post-surgical complications was designed to standardize the semiological concepts of post-surgical assessment. This scale will be assessed in a future investigation.

Uso de la Fibrina Rica en Plaquetas Inyectable (i-PRF) en Defectos Infra Óseos en Terapia Periodontal no Quirúrgica. Reporte de Dos Casos / Use of Injectable Platelet-Rich Fibrin (i-PRF) in Infra Osseous Defects in Non-Surgical Periodontal Therapy. Report of Two Cases

RESUMEN: Entre los concentrados plaquetarios de segunda generación, ha suscitado creciente interés, el uso de fibrina rica en plaquetas y leucocitos inyectable (i-PRF); que se obtiene a partir de la centrifugación inmediata de sangre venosa del propio individuo, y que aporta concentraciones elevadas de factor de crecimiento vascular endotelial, factor de crecimiento transformante beta, y factor de crecimiento derivado de plaquetas, entre otras proteínas que inician y coordinan el proceso reparativo. Su nula citotoxicidad y consistencia líquida abren un nuevo campo de estudio y experimentación en el ámbito de la Cirugía Oral y de la Periodoncia, como sustancia para irrigar. El objetivo de este manuscrito fue reportar el uso del i-PRF como irrigador subgingival en el tratamiento periodontal convencional de defectos infra óseos con 6 meses de seguimiento. En ambos casos, se verificó un efecto positivo de irrigación, lo que abre el debate al uso de productos farmacéuticos tradicionales como la clorhexidina versus preparados autólogos sin efectos adversos reportados a la fecha.

ABSTRACT: Second generation platelet concentrates include the use of injectable platelet-rich fibrin (i-PRF), which has generated increasing interest because it is derived from immediate centrifugation of venous blood from the patients themselves. It provides high concentrations of vascular endothelial growth factor, transforming growth factor beta, and platelet-derived growth factor, among other proteins that initiate and coordinate the healing process. Its null cytotoxicity and liquid consistency has opened new research lines in the field of oral surgery and periodontics, as an irrigation substance. The aim of this manuscript was to report the use of i-PRF, as a subgingival irrigator in conventional periodontal treatment of infra osseous defects, with six months follow-up. In both cases, a positive effect of irrigation was confirmed. These findings, open the debate as regards the use of traditional pharmaceutical products (such as chlorhexidine), versus autonomous preparations without adverse effects reported to date.

L-PRF y Ciclo Celular. Revisión Narrativa / L-PRF and cell cycle. Narrative Review

RESUMEN: Los concentrados plaquetarios han emergido como un potencial material regenerativo, utilizado de forma aislada o como andamiaje para otros materiales de injerto. Son extractos de sangre, obtenidos después de procesar una muestra de sangre completa, mediante centrifugación. El primer reporte data de 1970, con un CP utilizado como pegamento para mejorar cicatrización de heridas de piel. En 1998, se usaron en cirugía oral y maxilofacial. Desde entonces, se han desarrollado diferentes técnicas y una variedad de preparaciones. Entre ellas, cabe destacar el plasma rico en plaquetas, fibrina rica en plaquetas y leucocitos (L-PRF) y plasma rico en factores de crecimiento (PRGF). El desarrollo de estos biomateriales, se debe en parte, a la posibilidad de alterar la concentración de mediadores químicos liberados en una lesión que provoque la formación de un coágulo, que pueda madurar conforme transcurran las fases del proceso inflamatorio y concluya con la regeneración íntegra del tejido dañado. El objetivo de este manuscrito fue describir las principales vías de señalización intracelular que se activan en presencia del L-PRF en cirugía oral, y sus efectos en la regulación del ciclo celular.

ABSTRACT: Platelet concentrates (PC) have emerged as a potential regenerative material, used in isolation or as scaffolding for other graft materials. They are blood extracts, obtained after processing a sample of whole blood, by centrifugation. The first report dates from 1970, with a PC used glue to improve the healing of skin wounds. In 1998, they were used in oral and maxillofacial surgery. Since then, different techniques and a variety of preparations have been developed. These include platelet-rich plasma, fibrin rich in platelets and leukocytes (L-PRF) and plasma rich in growth factors (PRGF). The development of these biomaterials, is due in part to the possibility of altering the concentration of chemical mediators released in a lesion that causes the formation of a clot, which can mature as the phases of the inflammatory process pass and conclude with the complete regeneration of the damaged tissue. The aim of this manuscript was to describe the main intracellular signaling pathways that are activated in the presence of LPRF in oral surgery, and its effects on the regulation of the cell cycle.

[Second neoplasm after treatment of localized prostate cancer]. / Segunda neoplasia tras el tratamiento del cáncer prostático localizado.

INTRODUCTION: Prostate cancer (PC) treatment in early stages is radical prostatectomy (RP) or external radiotherapy (ER). There is some uncertainty regarding the development of new ER induced malignant tumors or second primary tumor (SPT), a fact influencing the choice of therapy. The purpose of this study is to determine the best therapeutic alternative for localized PC, in regards to incidence and time of development of. MATERIAL AND METHODS: A systematic review of the literature is proposed by means of evaluation of studies conducted with localized PC and treated with RP or ER, published between 1990 and 2010. The Mega searchers used were Cochrane Library and Trip Database, and the data bases used were MEDLINE, OVID, Science Direct, SciELO and LiLACS, using MeSH terms and free words. The studies selected were analyzed using the MINCIR score of methodological quality (MQ) to compare articles with different design. The variables were considered to be number of patients treated, localization of lesions, global incidence of STP and MQ of the studies. Averages, medians and weighted averages (WA) were calculated. The study groups were compared using the 95% confidence intervals of the medians. RESULTS: Eleven articles fulfilled the screening criteria (retrospective cohorts and case series); providing 13 series for the study. The average of MQ was 14.7 points (13 and 16 points). The most frequent localizations of STP were bladder, rectum and long. The WA of the global incidence of STP for the series was 3.6% (4.1% for ER and 2.2% RP) CONCLUSION: The information existing did not make it possible to demonstrated an association between the appearance of STP and therapies for localized PC, it even though there was a superior tendency in irradiated patients.

Instrucciones para la utilización de la escala mincir para valorar calidad metodológica de estudios de terapia / Instructions for the use of mincir scale to assess methodological quality in therapy studies

La calidad metodológica (CM) es un constructo multidimensional complejo que evalúa diferentes variables. Una aproximación al tema fue la generación de escalas para valorar CM de estudios de terapia, diagnóstico y pronóstico por parte de nuestro grupo de trabajo; todas ellas validadas. El objetivo de este artículo es entregar una pauta para estandarizar la aplicación para la escala MINCir, para valorar CM de estudios de terapia. Se realiza una descripción detallada de cada ítem y dominio que conforman la escala MINCir Terapia, junto con una guía de cómo dar respuesta a cada uno de ellos. Se generó una guía de usuario para aplicar la escala MINCir Terapia.

Methodological quality (MQ) is a complex multidimensional construct that tests different types of variables. An approach to this issue was the potential to generate a group of valid scales to assess MQ in therapy, diagnosis and prognosis studies. The aim of this article is to provide a guideline to standardize the implementation of a MinCir scale to assess MQ in therapy studies. A detailed description of each item and discipline of the therapy MinCir scale is provided, along with guidelines on how to respond each query. A user guide for applying the therapy MinCir scale was generated.

[24 hour esophageal pH monitoring in healthy individuals]. / Registro continuo de pH intraesofágico de 24 horas en individuos sanos.

BACKGROUND: Twenty four hour esophageal pH monitoring is considered the gold standard investigation for gastroesophageal reflux disease. This test allows the linkage of symptoms to occurrence of reflux episodes and is used to record the frequency of reflux and the amount of esophageal acid exposure that results from reflux. AIM: To know the acid esophageal exposure in healthy Chilean subjects. SUBJECTS AND METHODS: Thirty two asymptomatic volunteers aged 30 to 76 years old (24 female) underwent 24 h esophageal pH monitoring with a digitrapper Mark II Gold (Synectics Medical Stockholm). Total reflux episodes, episodes greater than 5 min, the longest reflux episode, the lapse with pH < 5, the percentage of time with pH < 4 and the score suggested by Johnson and De Mester were analyzed. RESULTS: There was a mean of 20.9 reflux episodes per subject and 0.1 episodes of more than 5 min. The longest episode lasted 8 min and the mean total time of acid reflux was 10 min/24 h. Total percentage pH below 4 was 0.7% and the mean score was 3.2. No subject reported symptoms during the test. CONCLUSIONS: For practical purposes, the upper limit of normal acid exposure in Chilean subjects is 2.4%.

Pilonidal disease: 25 cases treated by the Dufourmentel technique.

Twenty-five patients with pilonidal disease were treated by the Dufourmentel technique between 1984 and 1989. In this series, 18 patients (72 percent) were women and 7 (28 percent) were men (mean age, 24 years); hospital stay averaged 4 days. There were no recurrences and no reports of surgical wound infection. Diagnosis was confirmed histologically in all cases.

[Construction and validation of a gastroesophageal reflux symptom scale. Preliminary report]. / Construcción y validación de un instrumento de medición de síntomas de enfermedad por reflujo gastroesofágico. Informe preliminar.

BACKGROUND: Gastroesophageal reflux symptoms are frequent in the general population, but there is a lack of information about its prevalence and valid and reliable scales to determine it. AIM: To design a valid and reliable scale to determine gastroesophageal reflux disease. SUBJECTS AND METHODS: A Cross-sectional study with patients and controls was conducted. The diagnosis of gastroesophageal reflux was based of clinical plus radiological, endoscopic or pathologic criteria. A structured questionnaire was built, containing items covering different clinical manifestations of gastroesophageal reflux disease. All subjects were subjected to 24 h esophageal pH monitoring. Internal consistency of items, interobserver reliability, criterion and construct validity, sensitivity, specificity and predicted values were obtained. RESULTS: One hundred thirteen subjects (74 female and 39 male with a mean age of 46 years old) were studied. Seventy three had gastroesophageal reflux and 40 were controls. Internal consistency of the score was 0.82. Inter observer reliability was greater than 0.80 and a significant association was observed between the score and 24 h esophageal pH monitoring (p < 0.001). Instrument sensitivity was 97% and specificity 83%. CONCLUSIONS: The designed scale proved to be a valid and reliable instrument to measure gastroesophageal reflux symptoms, that can be used for future prevalence studies.

Effects of red wine on 24-hour esophageal pH and pressures in healthy volunteers.

The purpose of this study was to assess the effects of red wine taken with meals on esophageal motility, esophageal exposure to acid, and gastric pH. Following a randomized design, 14 healthy male volunteers (mean age 25 years, range 18-35 years were given 360 ml of red wine or tap water during lunch or dinner. All subjects underwent ambulatory 24-hr esophageal motility and esophagogastric pH monitoring studies. Three different periods were analyzed: during meals (30 min), postprandial (3 hr), and 8-hr supine. Two volunteers complained of heartburn after wine ingestion. An increase in the number of high amplitude waves (> 125 mm Hg, 95th percentile of our motility unit controls) was observed during meals accompanied by wine: water 1.2 (0-10.2), wine 1.6 (0-32.6), P = 0.02 [median (range)]. No other esophageal motility changes occurred. Percent reflux time increased during the postprandial period after wine ingestion in comparison with water: 1.7 (0-14.9) vs 0.1 (0-0.8), P < 0.05. Gastric pH was unaffected by the type of drink. Ingestion of moderate amounts of red wine with meals increases postprandial esophageal exposure to gastric acid in healthy persons.

Prevalence of esophageal disorders in patients with recurrent chest pain.

The objective of this study is to determine the prevalence of esophageal disorders (ED) associated with recurrent chest pain (RCP) and the utility of esophageal functional tests (EFT) in the study of these patients. The cross-sectional study was conducted at Hospital Clínico de La Frontera, Chile. One hundred and twenty-three patients with RCP were studied using esophageal manometry, edrophonium stimulation and 24-h pH monitoring. The performance of EFT was considered acceptable when they were capable of finding ED. To state the probability that RCP had an esophageal origin, patients were classified according to whether their pain had a probable, possible or unlikely esophageal origin. The prevalence of ED was determined according to diagnoses obtained after applying EFT and a multivariate analysis was performed to examine the association between the esophageal origin of RCP and ED. Rates of correct diagnosis of 65.9%, 56.9% and 31.7% was verified for 24-h pH monitoring, esophageal manometry and edrophonium stimulation, respectively. In 38.2% of patients with RCP, the pain was probably of esophageal origin, in 42.3% there was a possible esophageal origin and in 19.5% an unlikely esophageal origin. A 44.7% prevalence of GERD, 26.8% of GERD with secondary esophageal motor dysfunction and 8.9% of pure esophageal motor dysfunction were verified. The multivariate analysis allowed us to verify the association between the probability of esophageal origin of RCP, the variables RCP duration, esophagitis and dysphagia coexistence (P= 0.037, P= 0.030 and P= 0.024, respectively), and a statistically significant association between ED and dysphagia coexistence (P= 0.028). A high prevalence of ED was identified in patients with RCP.

[Cholangiohydatidosis. An evolutive complication of hepatic hydatidosis]. / Colangiohidatidosis. Una complicación evolutiva de la hidatidosis hepática.

Hydatidosis is and endemic disease in the south of Chile, especially in Region IX where remain rates of high prevalence. Cholangiohydatidosis is an infrequent complication of liver hydatidosis. The objective of this paper is to describe clinical features of a series of patients with cholangiohydatidosis. Series of cases of cholangiohydatidosis treated consecutively and the corresponding follow-up is reported. Clinical, laboratory and images characteristics are described. Descriptive statistic was used its incidence was calculated. In the studied period, 13 patients with cholangiohydatidosis were recruited, 9 men (69.2%) and 4 women (30.7%). Observed laboratory abnormalities were an increment of leukocytes in 8 patients (61.5%) and hepatic cholestasis with hepatocyte signs of cytolysis in 11 patients (84.6%). Choledocus diameter average measured by ultrasonography was 24.7 mm. All the patients had at least one liver cyst whose diameter average was of 12.1 cm. At surgery, evidence of biliary communications was detected in all patients and biliary decompression was carried out through a choledocostomy in 12 patients (92.3%) and by choledocoduodenal anastomoses in one case (7.7%). With a mean follow-up of 38.7 months morbility was 23% and mortality 7.7%. Accumulated incidence of this entity was of 0.07 cases in 5 years. Cholangiohydatidosis is an uncommon complication of liver hydatidosis that presents considerable morbidity and mortality rates.

[Hepatocellular carcinoma. General aspects of diagnosis and treatment]. / Carcinoma hepatocelular. Aspectos generales del diagnóstico y tratamiento.

Hepatocellular carcinoma is the most frequent form of primary hepatic cancer and has a high dissemination capacity. About 90% of tumors develop over a pre-existing cirrhosis but they also may occur in a normal liver. It has a higher frequency among males and 80% of tumors have clinical manifestations. It is associated to hepatitis B and C virus infection, alcoholism, cirrhosis of any etiology, consumption of aflatoxin Bl, oriental race and familial history. Patients are staged using classifications proposed by Okuda, Child-Pugh and the performance status test. Alpha feto protein is useful for diagnosis and follow up Abdominal ultrasound, hepatic scintiscan, angiography with lipiodol, CAT scan and nuclear magnetic resonance have a high diagnostic yield. Non surgical therapeutic alternatives include intratumoral alcoholization, chemoembolization and other such as tamoxifen and monoclonal antibodies. Surgical treatment is based on hepatic resection, whose magnitude depends on hepatic function. Hepatic transplantation is a new therapeutic alternative for patients in whom resection is not feasible and have a single small tumor without metastases.

[Carcinoma hepatocellular. Description of verified clinical characteristics in a region of Southern Chile]. / Hepatocarcinoma. Descripción de características clínicas verificadas en una Región del sur de Chile.

BACKGROUND: Hepatocellular carcinoma is the most frequent primary tumor of the liver. It is associated to chronic liver diseases and has a high prevalence in some regions of Africa and Asia. AIM: To describe the clinical characteristics of patients with hepatocellular carcinoma, admitted to two hospitals of the IX region of southern Chile. MATERIAL AND METHODS: Prospective study of 29 consecutive patients admitted to two hospitals in Temuco, Chile. Clinical features, laboratory values and viral markers were analyzed. RESULTS: Eighteen patients were male and ages ranged from 29 to 75 years old. The most frequent presenting symptom was abdominal pain in 21 patients. Seven subjects had a history of alcoholism. Serum bilirubin values ranged from 0.1 to 15.8 mg/dl, alkaline phosphatases ranged from 171 to 3476 U/l, ASAT from 24 to 5400 U/l and alpha feto protein from 1.4 to 350 ng/ml. Two patients had a positive hepatitis B surface antigen and all had negative hepatitis C virus antibodies. Mean tumoral diameter was 9.6 cm and the most common presentation was nodular. Mean survival after the diagnosis was 6.3 months. CONCLUSIONS: These patients with hepatocellular carcinoma have a low frequency of positive viral markers and tumors of large sizes on presentation.