GALV expression enhances the therapeutic efficacy of an oncolytic adenovirus by inducing cell fusion and enhancing virus distribution.

The limitations of the current oncolytic adenoviruses for cancer therapy include insufficient potency and poor distribution of the virus throughout the tumor mass. To address these problems, we generated an oncolytic adenovirus expressing the hyperfusogenic form of the gibbon-ape leukemia virus (GALV) envelope glycoprotein under the control of the adenovirus major late promoter. The oncolytic properties of the new fusogenic adenovirus, ICOVIR16, were analyzed both in vitro and in vivo, and compared with that of its non-fusogenic counterpart, ICOVIR15. Our results indicate that GALV expression by ICOVIR16 induced extensive syncytia formation and enhanced tumor cell killing in a variety of tumor cell types. When injected intratumorally or intravenously into mice with large pre-established melanoma or pancreatic tumors, ICOVIR16 rapidly reduced tumor burden, and in some cases, resulted in complete eradication of the tumors. Importantly, GALV expression induced tumor cell fusion in vivo and enhanced the spreading of the virus throughout the tumor. Taken together, these results indicate that GALV expression can improve the antitumoral potency of an oncolytic adenovirus and suggest that ICOVIR16 is a promising candidate for clinical evaluation in patients with cancer.

Abdominal tumors in patients with neurofibromatosis type I: Genotype-phenotype relationships.

BACKGROUND: Gastrointestinal stromal tumors have been detected in 25% of the necropsies performed on NF1 patients, but have been reported only in 7% of NF1 patients in the largest series. Such data imply an important gap between the true presence of tumors and those diagnosed. Few genotype-phenotype relationships have been described but to date none referring to abdominal tumors. OBJECTIVES: Evaluate retrospectively the efficacy of a regular and proactive follow-up of NF1 patients to early diagnose abdominal tumors and report their mutations. METHODS: Cohort study performed between 2010 and 2020, with 43 NF1 adult patients followed at our Dermatology department. RESULTS: Eight abdominal tumors were diagnosed in six patients, meaning that 14% of the followed patients developed an abdominal tumor. Five patients (83%) were asymptomatic. Five (83.3%) had a family history of NF1 with abdominal tumors (patients 1,2 and 3,4,5 were relatives). CONCLUSIONS: Although currently gastrointestinal routine screening investigations for asymptomatic patients are not recommended in the guidelines, the family aggregation in our series suggests it should be considered a close follow-up of the relatives of a patient with an NF1-related abdominal tumor. Also, for the first time, two mutations [c.2041C > T (p.Arg681Ter) and c.4537C > T (p.Arg1513*)] have been associated with family aggregation of abdominal tumors in NF1 patients.

Adjuvant therapy for true ampullary cancer: a systematic review.

BACKGROUND: Given the lack of evidence on the best adjuvant approach, this review closely examines optimal adjuvant management for resected true ampullary cancer and its histological subtypes. MATERIALS AND METHODS: A comprehensive literature search of PubMed was performed to identify studies on resected true ampullary cancers, published between January 2010 and December 2018. Data including the use of radiation, chemotherapy or chemoradiation and the outcomes were extracted. RESULTS: A total of 116 records were identified, of which 65 screened were selected. Finally, nine studies were included. Only two of the studies reported separately the outcomes of pancreatobiliary and intestinal subtypes. Patients in the selected studies were treated with a pancreaticoduodenectomy with negative margins. Patients treated with adjuvant therapy were more likely to be pT3-4 and have positive nodes; median survival ranged from 30 to 47 months. A significant benefit for adjuvant treatment was observed in four of the studies, restricted to patients at stage IIB or higher. Likewise, patients with positive nodes may have a longer median survival with adjuvant chemoradiation compared to observation. CONCLUSIONS: The present review suggests a benefit for adjuvant treatment for patients with locally advanced tumors. Randomized trials are needed to ascertain the topic, as well as studies reporting toxicity and quality of life of resected true ampullary cancer patients.

Atraumatic laparoscopic intraperitoneal mesh fixation using a new laparoscopic device: an animal experimental study.

PURPOSE: Laparoscopic ventral and incisional hernia repair (LVIHR) has become a common procedure because of its feasibility and safety, but it is not free of complications. Acute and chronic post-operative pain and bleeding caused by traumatic fixation of the mesh are frequently prolonging the hospital stay. The aim of this study was to analyze the behavior of n-butyl-cyanoacrylate (GLUBRAN® 2) as only mesh fixation METHODS: Ten female pigs were involved in the study and were divided into two groups of five (A and B). Animals in each group underwent a laparoscopic procedure in which two meshes were placed intraperitoneally and fixed with the same synthetic glue only. Animals in group A were sacrificed after 3 weeks, and those in group B were sacrificed after 12 weeks. We studied the morphological, biomechanical, and histological characteristics of the intraperitoneal mesh-tissue interface RESULTS: No disruption, migration or folding was observed in any of the pigs. In group A, the mean tensile strength was 1.4 N/cm (± 0.2) while in group B, the mean tensile strength was 2.5 N/cm (± 0.8). Histological analyses, in areas where mesh was fixed using the glue, showed a chronic lymphocytic inflammatory reaction with a granulomatous component and a marked desmoplastic reaction made up of immature collagen and numerous fibroblasts acquiring myofibroblastic characteristics. In some areas corresponding to fixation, the desmoplastic reaction originated from mature lamellar bone tissue with osteocytes and osteoblasts. CONCLUSION: Laparoscopic mesh fixation with only the synthetic comonomer glue GLUBRAN® 2 is feasible, effective, and safe in intraperitoneal incisional/ventral hernia repair in this animal model.

The use of gastric ultrasonography in the evaluation of a new antiflatulent preparation in human volunteers.

A method is described for inducing experimental aerogastria (flatulence) in human volunteers by the ingestion of "whipped" egg-white. Abdominal ultrasonography was used to measure the distension of the stomach and its interference with the visualization of organs such as gall bladder, pancreas and left kidney lying behind the stomach. A double-blind crossover comparison of Flatoril, a mixture of dimethicone (200 mg) and clebopride (0.5 mg) against placebo clearly demonstrated the superior antifoaming activity of the former both in terms of reduced gastric distension and of improved visualization of organs otherwise hidden by the foam-filled stomach.

[Gastric emptying in reflux esophagitis. Effect of metoclopramide and cinitapride]. / Vaciado gástrico en esofagitis por reflujo. Efecto de la metoclopramida y del cinitapride.

The gastric emptying of solids was evaluated with radionuclide techniques in 16 patients with reflux esophagitis, demonstrated by two of the following methods: endoscopy, pathology, and/or pH measurement. The percentage of radionuclide remaining within the stomach was 80.8 +/- 17% after 45 minutes, 63.3 +/- 10% after 75 minutes, and 48.8 +/- 19% after 105 minutes, with a half time (T1/2) of gastric emptying of 103.4 +/- 6 minutes. These results showed significant differences in T1/2 with those from a control group of healthy individuals, the gastric emptying being slower in patients with esophagitis (103.4 min vs 85.3 min; p less than 0.01). Subsequently, a double blind study to assess the effect of metoclopramide and cinitapride on gastric emptying in patients with reflux esophagitis was carried out. Cinitapride accelerated the gastric emptying of solids with statistically significant differences when compared with placebo (84 min vs 104 min, p less than 0.05). In this study, metoclopramide showed a tendency to accelerate gastric emptying, although it did not achieve a significant difference with placebo.

[Thorotrast-related hepatosis]. / Thorotrastosis hepática.

The clinical, pathological and laparoscopic data of five patients with liver disease due to Thorotrast are presented. Laparoscopy showed various degrees of fibrosis and nodularity. One patient developed cholangiocarcinoma and two showed dysplasia at biopsy. The laparoscopic appearance is practically diagnostic.

[Endoscopic cytology in the diagnosis of carcinoma of Vater's ampulla]. / Citología endoscópica en el diagnóstico de carcinoma de la ampolla de Vater.

An endoscopic cytology procedure was performed in 25 patients with a final diagnosis of carcinoma of the ampulla of Vater. A diagnosis of malignancy was made cytologically in 22 instances, and in 9 patients cytology was the only positive finding before operation. In two cases endoscopic biopsy was positive while the cytologic examination did not confirm the histological diagnosis.

[The accidents and complications of laparoscopy. A review of 8,915 cases]. / Accidentes y complicaciones de la laparoscopia. Revisión de 8.915 casos.

Complications occurring in 8,915 laparoscopies done during 1957-1991 are analyzed. Complications were classified as major or minor, according to the need of surgical intervention for their management, and also in relation to pneumoperitoneum, introduction of the laparoscope, during the examination or after laparoscopy. The total number of major accidents was 54 (0.60%). Half of them as a consequence of the instrumentation or of liver biopsy. There were 442 minor complications (4.96%). Mortality included 10 patients (0.11%) as a sequel of uncontrolled haemorrhage, 5 of them after liver biopsy. The complications of laparoscopy cannot be ignored; as all invasive techniques it may have a risk, even in the most expert hands. Half of the major accidents and of the mortality were due to complications from liver biopsy.

[Value of ultrasonography in the early diagnosis of hepatocellular carcinoma]. / Valor de la ecografía en el diagnóstico precoz del carcinoma hepatocelular.

The size and the treatment of 135 hepatocellular carcinomas (HCC) has been analyzed, comparing patients diagnosed by a US screening program (group 1) and these diagnosed outside this program (group 2) to determine whether US screening on patients with chronic liver disease is able to diagnose (HCC) at an early stage. alpha-fetoprotein levels above 500 U/ml were considered as diagnostic. Twenty (46.5%) out of 43 patients from group 1 showed a HCC < 5 cm. vs. 14/92 (15.2%) in group 2 (p = 0.001). Only 5.9% of the HCC < 5 cm. showed AFP > 500 U/ml. vs. 29.7% of the advanced HCC (p = 0.003). 88.3% of patients of group 1 vs. 63% of group 2 received specific treatment for HCC (p = 0.002). By means of US screening it is possible to diagnose HCC of smaller size and more susceptible to treatment. AFP is not useful in the early diagnosis of HCC.

[The duration of the effect of norfloxacin on the fecal flora in cirrhosis patients]. / Duración del efecto de la norfloxacina sobre la flora fecal en pacientes cirróticos.

The aim of the study has been to assess if intermittent treatment with norfloxacin could be able to maintain selective intestinal decontamination in cirrhotic patients in order to prevent bacterial infections. Group I (n = 10, subgroup Ia, n = 5, hospitalized cirrhotics, subgroup Ib, n = 5, outpatient cirrhotics) received 400 mg/24 h norfloxacin 7 days. Group II (n = 5, outpatient cirrhotics) received 400 mg/12 h norfloxacin 7 days. Gram-negative aerobic bacilli of the fecal floral were strongly suppressed in all patients at the end of the treatment, and they totally (Group I) or partially (Group II) recovered the initial concentrations 7 days after the end of the treatment. There were not significant differences between subgroups Ia and Ib. These results suggest that prophylactic treatment with norfloxacin in cirrhotic patients at high risk of infection should be continuous during the period in whom patients must be submitted to selective intestinal decontamination.

[Comparative multicentric study of omeprazole versus ranitidine in the treatment of duodenal ulcer]. / Estudio comparativo multicéntrico de omeprazol frente a ranitidina en el tratamiento de la úlcera duodenal.

A total of 158 patients, aged 19-78 years and with endoscopically verified duodenal ulcer of at least 5 mm in maximum diameter were recruited. 79 patients were randomised to treatment with omeprazole, a proton-pump inhibitor of the parietal cell, and 79 patients were treated with ranitidine. This double blind study is the first clinical trial with omeprazole in Spain. Using "intention to treat" analysis there was no difference in healing rates at 2 weeks between the omeprazole group (70%) and the ranitidine group (59%) with p = 0.13. At four weeks, however, omeprazole healed significantly more patients (92%) than ranitidine (76%) with p = 0.005. Using per protocol analysis a similar result was obtained with no significant difference between omeprazole (71%) and ranitidine (63%) at two weeks (p = 0.3) but significantly greater healing on omeprazole at 4 weeks (97%) compared with ranitidine (83%) with p = 0.008. The influence of additional prognostic factors was assessed using a multivariate analysis. At two and four weeks, there was a significant effect of ulcer size on healing rate. At four weeks there was also a significant effect of treatment. Symptom relief was rapid in both treatments but the omeprazole group had significantly fewer days of pain and better patient's overall evaluation than ranitidine group. No serious adverse events were reported. In conclusion omeprazole healed significantly more duodenal ulcers than ranitidine and symptom relief was more rapid during omeprazole therapy.

Education and training in gastroenterology. Report from the OMGE symposia at the International Congress of Gastroenterology, Lisbon, Portugal, September 1984, and at the 8th World Congress of Gastroenterology, São Paulo, Brazil, September 1986.

Gastroenterology is recognized as a speciality in most countries, especially in Europe and North America. The requirements for being acknowledged as a specialist vary from 1 1/2 to 4 years of training and education in gastroenterology in addition to 1-6 years of training and education in internal medicine/surgery. The requirement of theoretical education varying from 40 to 300 h is practiced in some countries only. In some countries training in endoscopy is separated from gastroenterology. A formal examination and post-specialization training program is required in only some of the countries answering the questionnaire. The number of centres per million inhabitants recognized for training and education also varied greatly. The number of specialists per million inhabitants was 3.6 to 15. In the Middle and Far East the organisation of gastroenterology was much inferior to that in Europe and North America because of insufficient education and organization programs and lack of economic support to perform them. The answers from the gastroenterological associations and personal reporters agreed on the following: A speciality in medical and surgical gastroenterology should be established in all countries around the world. Programs for training and education should be agreed upon in recognized teaching and training institutions of gastroenterology, probably of 3 years' duration in combination with a speciality in internal medicine. A gastroenterologist will in most cases be dealing with other diseases as well. The number of specialists per million inhabitants may be estimated to 10, the exact number not being possible to determine at present. In most countries the post-specialization programs were not required but were offered, a problem that has to be clarified.(ABSTRACT TRUNCATED AT 250 WORDS)

Guidelines for biomarker testing in gastroenteropancreatic neuroendocrine neoplasms: a national consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology.

The annual incidence of neuroendocrine tumours in the Caucasian population ranges from 2.5 to 5 new cases per 100,000 inhabitants. Gastroenteropancreatic neuroendocrine tumours is a family of neoplasms widely variable in terms of anatomical location, hormone composition, clinical syndromes they cause and in their biological behaviour. This high complexity and clinical heterogeneity, together with the known difficulty of predicting their behaviour from their pathological features, are reflected in the many classifications that have been developed over the years in this field. This article reviews the main tissue and clinical biomarkers and makes recommendations for their use in medical practice. This document represents a consensus reached jointly by the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Pathology (SEAP).