Volvulus of a wandering spleen in a pediatric patient.

Wandering spleen is a rare condition in children that is often caused by the loss or weakening of the splenic ligaments. Its clinical presentation is variable; 64% of children with wandering spleen have splenic torsion as a complication. A 13-year-old boy who had been showing abdominal pain in the hypogastric region accompanied by vomit and an enormous tumefaction in the suprapubic region came to our observation. Considering the ovoid morphology at ultrasound exam, the echostructure and the marked reduction of parenchymal vascularization, suspicion for torsion of an ectopic spleen arose. Ultrasound evaluation has a primary role in the diagnosis of a suspected wandering spleen and, to avoid potentially life-threatening complications, immediate surgery is often times required.

Magnetic foreign body ingestion in pediatric age.

OBJECTIVES: To assess the clinical complications reported after the ingestion of magnetic foreign bodies (FBs) in pediatric age, along with their incidence among all FB ingestions and clinical presentation. STUDY DESIGN: We've consecutively recruited all children aged 0-14 years who were admitted for single or multiple magnet ingestion from May 2015 to December 2022. Patient demographics, admission sources and discharge status were accurately recorded, along with their clinical management and outcomes. RESULTS: Sixty-one children were enrolled, of whom 49/61 (80.3%) had ingested a single magnet and 12/61 (19.7%) multiple magnets. Only 1/49 children with single magnet required endoscopic removal due to esophageal retention. Among children having ingested multiple magnets, 5/12 (41.7%) undergo endoscopic removal since magnets were amenable to endoscopic retrieval whereas in 7/12 (58.3%) magnets could not be promptly removed. Among these, 4/12 (33.3%) later developed intestinal ischemia/necrosis or perforation and required FB surgical intervention whereas 3/12 (25%) uneventfully evacuated magnets. CONCLUSIONS: Our data confirm that multiple magnet ingestion, unlike single magnet ingestion, pose a serious health hazard. Parents and caregivers should remove them from the reach of children. Medical providers should maintain a high index of suspicion of their ingestion since prompt evaluation and likely removal may be lifesaving and intestine saving.

Long gap esophageal atresia repair using the foker tecnique: a 19 years experience.

Esophageal atresia (EA) with a 3-cm gap or longer and a very short distal segment represents the extreme of this disorder's spectrum, the treatment of which can be challenging. Management of newborns with long-gap esophageal atresia (LGEA) remains a challenge for pediatric surgeons. The inclusion criteria in the study were as follows: long gap esophageal atresia, Foker technique, at least 10 years follow up. We sought to examine our experiences with LGEA using Foker technique. RESULTS: From 2001 to 2020 were operated for esophageal atresia at the UOC Surgery of the AORN Santobono 290 children of whom 16 patients meet our inclusion criteria. 6 had a type I EA, 2 had a type II and 8 had a type III. Mean gap length was 4 cm (range 3-5), In 9 patients gastrostomy and Foker technique was performed in the same time (around the 1stto the 4th day of life), while in 7 patients gastrostomy was performed in 1st-2nd day of life and the Foker technique was delayed due to clinical needs with a mean of 76 days (range 26-96 days) . In the study group, 11/16 (68,75%) patients underwent multiple endoscopic dilatations ( means 5 sessions per patient); 3 out of 16 cases of early complications occurred: 2 perforations and 1 dehiscence. Gastroesophageal reflux was common during the first 6 years of life and 2 had a fundoplication due to gastroesophageal reflux disease resistant to maximal medical therapy and 1 had an esophageal diverticulum at 5 years. 7 out of 16 (43,7%) (average age 13,5 years) perform therapy cycles with pump inhibitors for an average period of 12 weeks. CONCLUSIONS: Foker procedure for esophageal lengthening in patients with LGEA was successful in mobilizing the esophagus and obtaining a repair in the majority of our patients after 12 to 15 days of traction and it should be considered in LGEA cases to preserve the native esophagus as often as possible.

Gastrointestinal function after surgical correction of Hirschsprung's disease: long-term follow-up in 81 patients.

BACKGROUND: Despite significant developments in understanding the pathological anatomy and physiology of Hirschsprung's disease (HD), the follow-up of children with HD remains far from clear. Treatment results for HD are not uniformly successful and the interpretation of the result by the parents and child may differ from that of the surgeon. Our goal is to analyze quality of life and differences in functional outcomes in children operated on using the pediatric incontinence / constipation scoring system (PICSS) validated in a regulatory group. METHODS: A retrospective questionnaire was performed for all children operated for HD between 1995 and 2017 at the Pediatric Surgery Unit. The use of PICSS defined children with continence or incomplete constipation. RESULTS: 125 patients were operated on for HD between 1995 and 2017 in our Pediatric Surgery Unit and 81 families gave their consent to participate. The median age at the interview was 94.5 months (range 12-283 months). Complete aganglionosis was in 2% of cases. Treatments included a Soave procedure in 96%. Colostomy was performed in 15.8% (13/81). Decompressive enterostomy was performed in a child. The rate of normal bowel function was 66.6% (n = 54). The percentage of cases with incomplete continence and with constipation were 4.9% (n = 4) and 16% (n = 13), respectively. CONCLUSIONS: HD results aren't always as good as surgeons may perceive; long-term follow-up is important. Over time, most schoolage children improve significantly for fecal continence, but it can also be acquired in late adolescence.

Computational Analysis of Dipyrone Metabolite 4-Aminoantipyrine As A Cannabinoid Receptor 1 Agonist.

BACKGROUND: Cannabinoid receptor 1 has its crystallographic structure available in complex with agonists and inverse agonists, which paved the way to establish an understanding of the structural basis of interactions with ligands. Dipyrone is a prodrug with analgesic capabilities and is widely used in some countries. Recently some evidence of a dipyrone metabolite acting over the Cannabinoid Receptor 1has been shown. OBJECTIVE: Our goal here is to explore the dipyrone metabolite 4-aminoantipyrine as a Cannabinoid Receptor 1 agonist, reviewing dipyrone characteristics, and investigating the structural basis for its interaction with the Cannabinoid Receptor 1. METHOD: We reviewed here recent functional studies related to the dipyrone metabolite focusing on its action as a Cannabinoid Receptor 1 agonist. We also analyzed protein-ligand interactions for this complex obtained through docking simulations against the crystallographic structure of the Cannabinoid Receptor 1. RESULTS: Analysis of the crystallographic structure and docking simulations revealed that most of the interactions present in the docked pose were also present in the crystallographic structure of Cannabinoid Receptor 1 and agonist. CONCLUSION: Analysis of the complex of 4-aminoantipyrine and Cannabinoid Receptor 1 revealed the pivotal role played by residues Phe 170, Phe 174, Phe 177, Phe 189, Leu 193, Val 196, and Phe 379, besides the conserved hydrogen bond at Ser 383. The mechanistic analysis and the present computational study suggest that the dipyrone metabolite 4-aminoantipyrine interacts with the Cannabinoid Receptor 1.

Advances in the Understanding of the Cannabinoid Receptor 1 - Focusing on the Inverse Agonists Interactions.

BACKGROUND: Cannabinoid Receptor 1 (CB1) is a membrane protein prevalent in the central nervous system, whose crystallographic structure has recently been solved. Studies will be needed to investigate CB1 complexes with its ligands and its role in the development of new drugs. OBJECTIVE: Our goal here is to review the studies on CB1, starting with general aspects and focusing on the recent structural studies, with emphasis on the inverse agonists bound structures. METHODS: We start with a literature review, and then we describe recent studies on CB 1 crystallographic structure and docking simulations. We use this structural information to depict protein-ligand interactions. We also describe the molecular docking method to obtain complex structures of CB 1 with inverse agonists. RESULTS: Analysis of the crystallographic structure and docking results revealed the residues responsible for the specificity of the inverse agonists for CB 1. Most of the intermolecular interactions involve hydrophobic residues, with the participation of the residues Phe 170 and Leu 359 in all complex structures investigated in the present study. For the complexes with otenabant and taranabant, we observed intermolecular hydrogen bonds involving residues His 178 (otenabant) and Thr 197 and Ser 383 (taranabant). CONCLUSION: Analysis of the structures involving inverse agonists and CB 1 revealed the pivotal role played by residues Phe 170 and Leu 359 in their interactions and the strong intermolecular hydrogen bonds highlighting the importance of the exploration of intermolecular interactions in the development of novel inverse agonists.

Survey of KRAS, BRAF and PIK3CA mutational status in 209 consecutive Italian colorectal cancer patients.

Molecular testing for KRAS and BRAF mutations in tumor tissue is a fundamental tool to identify patients with metastatic colorectal cancer (CRC) who are eligible for anti-EGFR monoclonal antibody therapy. We here report a molecular analysis by high-resolution melting analysis and direct sequencing of KRAS, BRAF and PIK3CA hot spot mutations in 209 Italian CRC patients. One hundred and ten patients (51%) were identified who were potentially nonresponders to anti-EGFR therapy: 90/209 patients (43%) harboring KRAS mutations, 13/117 (11.1%) with the V600E BRAF mutation, and 7/209 (3.3%) with mutations in PIK3CA exon 20. The prevalence of BRAF and PIK3CA mutations was significantly higher in patients older than 65 years (p=0.014 and p=0.018), while patients with triple-negative tumors were significantly younger than mutation carriers (p=0.000011). Patients with gene mutations also showed a trend towards preferential tumor location in the colon (p=0.026). Moreover, although involving a relatively small number of samples, we report the presence of a discordant mutational profile between primary tumors and secondary lesions (3/9 patients), suggesting that it is worthwhile to test other available tissues in order to better define the efficacy of targeted therapy. Further correlations of specific clinical features with tumor mutational profile could be helpful to predict the response of CRC patients to monoclonal antibody therapy.

Blocking p38/ERK crosstalk affects colorectal cancer growth by inducing apoptosis in vitro and in preclinical mouse models.

We recently demonstrated that p38α is required to maintain colorectal cancer (CRC) metabolism, as its inhibition leads to FoxO3A activation, autophagy, cell death, and tumor growth reduction both in vitro and in vivo. Here we show that inhibition of p38α is followed by TRAIL-mediated activation of caspase-8 and FoxO3A-dependent HER3 upregulation with consequent overactivation of the MEK-ERK1/2 survival pathway. p38α and MEK combined inhibition specifically induces apoptosis by enabling TRAIL signaling propagation through t-Bid and caspase-3, and fosters cell death in CRC cells and preclinical mouse models. Current MEK1-directed pharmacological strategies could thus be exploited, in combination with p38α inhibition, to develop new approaches for CRC treatment.

Retrobulbar metastasis from gallbladder carcinoma after laparoscopic cholecystectomy. A case report.

Extra-abdominal metastases from gallbladder cancer are very rare; the sites outside the abdomen most frequently affected are the skin, bone and central nervous system. In the literature, only one case of orbital metastasis from gallbladder cancer has been reported, in a patient previously treated by open cholecystectomy. We report the case of a 53-year-old woman who underwent a laparoscopic cholecystectomy for symptomatic gallbladder stones. Postoperative histological examination revealed an unsuspected gallbladder adenocarcinoma. One month later she came to our observation after having developed diplopia and ophthalmic pain due to an orbital metastasis. We decided not to perform a surgical second look because of the already rapid dissemination of the malignant tumor. The few cases of uncommon gallbladder cancer metastases after laparoscopic cholecystectomy described in the literature are discussed, as well as the possible role of laparoscopy in the dissemination and localized seeding of malignant cells.

[Granular cell tumors of the colon. Clinical case and review of the literature]. / Tumori a cellule granulose del colon. Caso clinico e revisione della letteratura.

Abrikossoff's tumours are better known as granular cell tumours because of the typical microscopic aspect of their cytoplasm. They are uncommon neoplasms, probably of neurogenic origin, typically subepithelial and often benign. Rarely, they may be localised in the digestive tract, where they are mostly asymptomatic and tend to be discovered incidentally during endoscopic examinations indicated for other diseases. Histological examination with immunohistochemical staining usually yields the definitive diagnosis. Most authors agree as to the indication for endoscopic resection because of the possible, though rare, aggressive biological behaviour of these tumours. In the present paper we report on a case of granular cell tumour of the caecum, endoscopically resected and staining positively at the immunohistochemical search for the S100 protein.

Human anisakiasis in Italy: a report of eleven new cases.

The authors report on eleven new human cases of anisakiasis occurring in Italy, and emphasize the importance of the infection in clinical medicine, histopathology and public health. For ten of these cases, the diagnosis was based on histological findings: an eosinophilic granuloma associated with a larva of Anisakis sp. For one of them, the larva was removed from the stomach by endoscopy. Nine of the subjects were from Apulia and two from Molise (regions of southern and central Italy, respectively). Ten of them were surgically treated, and in one case the endoscopical extraction of the parasite resolved the situation. In two cases, the gastric wall was affected, in three the intestinal wall, in a further three the omentum, in one the spleen, and in the final two the mesentery and the epiploic appendix. In all the cases, the parasite was discovered unexpectedly during surgical treatment of the patients for supposed illnesses, which had originally been misdiagnosed. In three cases, the patients were also affected by cancer. Human anisakiasis must be taken into account in the differential diagnosis of acute, abdominal synddromes in subjects who have ingested raw fish or squid a few hours to a few days before the onset of symptoms. Histopathologists should consider the possibility of this parasitic infection when confronted with an eosinophilic granuloma of the digestive tract, mesentery or peritoneum. The incidence of anisakiasis in Italy is probably higher than reported, as some cases might not be diagnosed and others might heal spontaneously.