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.

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).

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.

Nuclear IKK activity leads to dysregulated notch-dependent gene expression in colorectal cancer.

Nuclear functions for IkappaB kinase (IKK), including phosphorylation of histone H3 and nuclear corepressors, have been recently described. Here, we show that IKK is activated in colorectal tumors concomitant with the presence of phosphorylated SMRT (silencing mediator of retinoic acid and thyroid hormone receptor) corepressor that is aberrantly localized in the cytoplasm. In these tumors, IKKalpha associates to the chromatin of specific Notch targets, leading to the release of SMRT. Abrogation of IKK activity by BAY11-7082 or by expressing dominant negative IKKalpha restores the association of SMRT with Notch target genes, resulting in specific gene repression. Finally, BAY11-7082 significantly reduces tumor size in colorectal cancer xenografts (CRC-Xs) implanted in nude mice.

Prevalence of thyroid autoantibodies is not increased in blood donors with hepatitis C virus infection.

Serum autoimmune reactions are found in many patients with hepatitis C. A high prevalence of thyroid dysfunction and antithyroid antibodies in patients with chronic hepatitis C was recently reported. We have compared the prevalence of thyroid dysfunction and antithyroid peroxidase antibodies in blood donors with hepatitis C virus (HCV) infection (study group) and in seronegative anti-HCV donors (control group). One hundred and ninety-two blood donors were studied: 96 were anti-HCV positive by ELISA 2 (48 males and 48 females; age 48 +/- 12.9 years, mean +/- SD), and 96 were HCV seronegative (55 males and 41 females; age 37 +/- 14.8 years). In all patients, serum TSH (0.25-4.2 mU/l) and fT4 (9-23 pmol/l) were measured by immunochemiluminiscent assays and antithyroid peroxidase antibodies (normal < 100 U/ml) by RIA. In all anti-HCV positive donors, hepatitis C viremia was tested using the nested polymerase chain reaction. Thyroid dysfunction was found in three females (3.1%) in the anti-HCV positive group (three cases of hypothyroidism), and in four (4.1%) anti-HCV negative blood donors (three cases of hypothyroidism, two females and one male; one case of hyperthyroidism, a female), (p = NS). Antithyroid peroxidase antibody titers were above normal values in 5 (5.2%) anti-HCV positive individuals and in eight (8.3%) anti-HCV negative blood donors (p = NS). These results do not show an increase prevalence of thyroid dysfunction and antithyroid peroxidase antibodies in blood donors with HCV infection when compared with a control group.

Omeprazole versus ranitidine as adjunct therapy to endoscopic injection in actively bleeding ulcers: a prospective and randomized study.

BACKGROUND AND STUDY AIMS: Although high rates of initial hemostasis can be achieved with endoscopic injection therapy in actively bleeding ulcers, the incidence of rebleeding is not negligible. Optimal conditions for clotting may require achieving deep and sustained acid inhibition to avoid the deleterious effect of acid and pepsin secretions on the hemostatic process. The aim of this study was to assess whether omeprazole could improve the efficacy of ranitidine as an adjunct treatment in endoscopic injection therapy to avoid rebleeding. PATIENTS AND METHODS: Eighty-six patients with active arterial bleeding from a peptic ulcer disclosed at emergency endoscopy were included in this prospective trial. All patients received injections of 1:10,000 adrenaline. Subsequently, they were randomized to receive either intravenous omeprazole (n = 45), with an initial dose of 80 mg followed by 40 mg every eight hours for four days and thereafter with oral administration; or ranitidine (n = 41), 50 mg every six hours for 12 to 24 hours and thereafter with oral administration. RESULTS: The two groups were well matched in terms of clinical and endoscopic data. There were no statistically significant differences between the groups with regard to: further bleeding (29% in both groups), need for emergency surgery (20% in the omeprazole group vs. 22% in the ranitidine group), transfusion requirements (2.4 +/- 2.2 vs. 2.2 +/- 2.1 units), length of hospital stay (14.1 +/- 13.9 vs. 15.3 +/- 15.4 days), or mortality (7% vs. 2%). CONCLUSIONS: Our results suggest that omeprazole does not improve the efficacy of ranitidine after endoscopic injection therapy in patients with an active arterial bleeding ulcer.

Controlled trial of tamoxifen in patients with advanced hepatocellular carcinoma.

Thirty-six consecutive patients with advanced hepatocellular carcinoma and chronic liver disease were randomly allocated to two groups: group I included 20 patients who were treated with 10 mg bid. tamoxifen and group II with 16 non-treated patients. The two groups were homogeneous according to clinical and analytical data. Survival curves in the tamoxifen-treated patients improved significantly when compared with the non-treated group (p = 0.01). Cumulative survival at the end of the first year was 48.5% in the treated patients and 9.1% in controls. Median survival was 261 days in the treated group vs. 172 in the non-treated group (p < 0.05). Complications of cirrhosis and worsening of the performance status test occurred less in the treated patients than in the controls, but not significantly so. Tamoxifen was well tolerated and no marked side effects were observed. In this series, tamoxifen improved survival in patients with advanced hepatocellular carcinoma.

Value of second-look endoscopy after injection therapy for bleeding peptic ulcer: a prospective and randomized trial.

A prospective and randomized trial involving 104 patients was performed to assess whether second-look endoscopy could improve the efficacy of injection therapy for bleeding ulcers. The inclusion criteria were the presence of active arterial bleeding or a non-bleeding visible vessel at emergency endoscopy. All the patients received emergency injection of 1:10,000 adrenaline and were subsequently randomized (52 patients in each group) according to whether or not they would receive a second elective endoscopy within the first 24 hours with repeated injection if a visible vessel was still identified. Both groups were well matched for clinical and endoscopic data. A tendency towards better results was noted in the group that received a second-look endoscopy; the two groups were compared in regard to further bleeding (21% versus 29%, 95% confidence interval of the difference = -24.3 to 8.5), need for emergency surgery (8% versus 15%, 95% confidence interval of the difference = -19.9 to 4.5), transfusion requirements (1.7 +/- 1.9 versus 2.5 +/- 2.5 units, 95% confidence interval of the difference = -1.6 to 0.07), length of hospital stay (9.3 +/- 8.6 versus 11.8 +/- 10.8 days, 95% confidence interval of the difference = -6.2 to 1.4), and mortality rate (2% versus 4%). Although these trends did not achieve statistical significance, a type II error cannot be ruled out. However, according to our results, several hundred patients would be required to demonstrate statistically these relatively small differences.(ABSTRACT TRUNCATED AT 250 WORDS)

[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.

Endoscopic injection therapy of bleeding ulcer: a prospective and randomized comparison of adrenaline alone or with polidocanol.

In a prospective randomized trial involving 63 patients with bleeding peptic ulcer, we assessed whether the addition of 1% polidocanol improved the results achieved by 1/10(4) adrenaline alone for injection therapy. The inclusion criterion was the presence of active arterial bleeding or a nonbleeding visible vessel at emergency endoscopy. Thirty patients were treated with 1/10(4) adrenaline (group A) and 33 with adrenaline plus 1% polidocanol (group B). Initial hemostasis was achieved in 97% of cases in both groups and permanent hemostasis in 87% patients in group A and in 76% in group B (p = NS). Mortality was 6% in group A and 3% in group B. There were no differences between the two groups regarding requirements for emergency surgery, the number of transfusions, or the length of hospital stay. One patient in group B had a perforation. No other relevant complications were noted. In conclusion, combined therapy does not improve the results achieved with adrenaline alone.

Is endoscopic gastric cytology worthwhile? An evaluation of 903 cases of carcinoma.

From 1978 to 1989, 4,772 endoscopic cytological examinations of the stomach have been done in our laboratory, including 903 patients with a final diagnosis of gastric carcinoma. There were seven false-positive results among 3,810 examinations done in patients without malignant disease (specificity 99.8%). Cytology yielded positive results in 785 of 903 carcinomas (sensitivity 86.9%), while biopsies were positive in 826 of 895 cases (sensitivity 92.3%). Both techniques combined resulted in positive diagnoses in 886 of 903 malignancies (sensitivity 98.1%). Cytology was positive in 52 patients with negative biopsies as well as in eight patients in whom biopsies had not been obtained. Thus cytology added 60 positive diagnoses (6.7%) to the overall diagnostic results. These results suggest that endoscopic cytology is useful for avoiding unnecessary delays caused by having to perform repeated endoscopic biopsies. It should be done as a routine procedure in those institutions in which significant numbers of gastric carcinomas are studied and where an experienced gastrointestinal cytology laboratory is available.

[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.

[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.