Low doses of ionizing radiation activate endothelial cells and induce angiogenesis in peritumoral tissues.

PURPOSE: During radiotherapy the peritumoral tissues are daily exposed to subtherapeutic doses of ionizing radiation. Herein, the biological and molecular effects of doses lower than 0.8 Gy per fraction (LDIR), previously described as angiogenesis inducers, were assessed in human peritumoral tissues. MATERIAL AND METHODS: Paired biopsies of preperitoneal adipose tissue were surgically collected from 16 patients diagnosed with locally advanced rectal cancer who underwent neo-adjuvant radiotherapy. One of the biopsies is located in the vicinity of the region where the tumor received the prescribed dose of radiation, and thus exposed to LDIR; the other specimen, outside all beam apertures, was used as an internal calibrator (IC). Microvessel density (MDV) was quantified by immunohistochemistry and the expression of angiogenic, pro-inflammatory, adhesion and oxidative stress genes was assessed by quantitative RT-PCR using exclusively endothelial cells (ECs) isolated by laser capture microdissection microscopy. RESULTS: LDIR activated peritumoral ECs by significantly up-regulating the expression of several pro-angiogenic genes such as VEGFR1, VEGFR2, ANGPT2, TGFB2, VWF, FGF2, HGF and PDGFC and down-regulating the pro-inflammatory IL8 marker. Accordingly, the MVD was significantly increased in peritumoral tissues exposed to LDIR, compared to the IC. The patients that yielded a larger pro-angiogenic response, also showed the highest MVD. CONCLUSIONS: LDIR activate ECs in peritumoral tissues that are associated with increased MVD. Although the technological advances in radiotherapy have contributed to reduce the damage to healthy tissues over the past years, the anatomical regions receiving LDIR should be taken into account in the treatment plan report for patient follow-up and in future studies to correlate these doses with tumor dissemination.

A fetus with an immature umbilical cord teratoma associated with exomphalos: case report and review of the literature.

OBJECTIVE: To describe the antenatal and pathological features of an immature umbilical cord teratoma associated with exomphalos, and to review the literature on this subject. CASE PRESENTATION: An abdominal wall defect, suspected to be an exomphalos, was identified during routine ultrasound examination performed at 13 weeks of gestation. The pregnancy was terminated. Fetopathological examination revealed an immature umbilical cord teratoma associated with exomphalos. Chromosomal microarray analysis was normal. CONCLUSIONS: Umbilical cord teratomas, albeit very rare, should be emphasized as a possible differential diagnosis when abdominal wall defects are detected. Since cord teratomas may lead to adverse fetal or neonatal outcomes, close follow-up of the fetus is recommended.

Efficacy, Safety, and Sample Quality of Ultrasound-Guided Synovial Needle Biopsy in Clinical Practice and Research: A Prospective Observational Study.

OBJECTIVE: To study the efficacy, tolerability, safety, and sampling variation of ultrasound (US)-guided synovial biopsies performed in clinical practice and research. METHODS: We included all patients who had a US-guided synovial needle biopsy from November 2013 to January 2018. Patients were evaluated for procedure safety and tolerability. Usefulness of synovial biopsy was considered based on contribution for achieving the proposed aims. We analyzed samples for presence and quality of synovial tissue, synovitis score/grade, and pathotype. Variation across patients, samples, section levels, and sampling order was assessed. RESULTS: A total of 64 US-guided synovial biopsies were performed (n = 52 in clinical practice, n = 12 in research). Patient tolerability (70% no/mild discomfort) was remarkably high. There was no significant aggravation of symptoms or US synovitis in the biopsied joint. Procedures were overall safe, with few minor, 2 moderate, and no major adverse events. Usefulness of US-guided synovial biopsies was high, both in clinical practice (37% direct diagnostic impact, 100% positive/95% negative predictive values for infection) and in research (92% success). Synovial tissue was retrieved in 88% of biopsies, with a median of 75% gradable samples. There was significant variation in sample quality and synovitis features across patients and samples, but not between different section levels. Samples collected later in the procedure had a lower frequency of synovial tissue and were poorly concordant in pathotype with those collected earlier. CONCLUSION: US-guided synovial needle biopsy is an effective, safe, and well-tolerated means to collect good quality synovial tissue for clinical and research purposes. Samples collected for different aims should be retrieved in parallel, rather than sequentially.

Low doses of ionizing radiation activate endothelial cells and induce angiogenesis in peritumoral tissues.

PURPOSE: During radiotherapy the peritumoral tissues are daily exposed to subtherapeutic doses of ionizing radiation. Herein, the biological and molecular effects of doses lower than 0.8 Gy per fraction (LDIR), previously described as angiogenesis inducers, were assessed in human peritumoral tissues. MATERIAL AND METHODS: Paired biopsies of preperitoneal adipose tissue were surgically collected from 16 patients diagnosed with locally advanced rectal cancer who underwent neo-adjuvant radiotherapy. One of the biopsies is located in the vicinity of the region where the tumor received the prescribed dose of radiation, and thus exposed to LDIR; the other specimen, outside all beam apertures, was used as an internal calibrator (IC). Microvessel density (MDV) was quantified by immunohistochemistry and the expression of several pro-angiogenic genes was assessed by quantitative RT-PCR using exclusively endothelial cells (ECs) isolated by laser capture microdissection microscopy. RESULTS: LDIR activated peritumoral ECs by significantly up-regulating the expression of several pro-angiogenic genes such as VEGFR1, VEGFR2, ANGPT2, TGFB2, VWF, FGF2, HGF and PDGFC. Accordingly, the MVD was significantly increased in peritumoral tissues exposed to LDIR, compared to the IC. The patients that yielded a larger pro-angiogenic response, also showed the highest MVD. CONCLUSIONS: LDIR activate ECs in peritumoral tissues that are associated with increased MVD. Although the technological advances in radiotherapy have contributed to reduce the damage to healthy tissues over the past years, the anatomical regions receiving LDIR should be taken into account in the treatment plan report for patient follow-up and in future studies to correlate these doses with tumor dissemination.

Signet Ring Cell Carcinoma, Ileal Crohn Disease or Both? - A Case of Diagnostic Challenge.

Signet ring cell carcinoma is a rare form of adenocarcinoma that predominantly affects the stomach. Signet ring cell carcinoma originated from the ileum is extremely rare and the prognosis is poor. We present a case of small bowel obstruction with features suggesting Crohn disease of the ileum. The symptoms were chronic diarrhea and abdominal pain with a family history of inflammatory bowel disease. The patient underwent surgery and histopathology revealed both aspects of signet ring cell carcinoma and Crohn disease of the ileum. An association between long-standing inflammation and the development of this subtype of tumor has been proposed but there are no established surveillance guidelines for small bowel neoplasm in inflammatory bowel disease.

O carcinoma de células em anel de sinete é uma forma rara de adenocarcinoma que afeta predominantemente o estômago. A forma primária do íleon é muito rara e apresenta mau prognóstico. Apresentamos um caso de doença de Crohn do íleon cuja forma de apresentação cursou com quadro oclusivo associado a adenocarcinoma de células em anel de sinete do íleon. A doente apresentava história prévia de diarreia crónica e tinha história familiar de doença inflamatória. Foi submetida a ressecção cirúrgica e os achados histopatológicos revelaram a presença de aspetos compatíveis com doença de Crohn do íleon e adenocarcinoma de células em anel de sinete. Foi proposta uma associação com esta forma rara de tumor e inflamação de longa duração, contudo, não existem recomendações estabelecidas de vigilância de neoplasia na doença inflamatória intestinal com atingimento ileal.

A case of post-radiotherapy gastritis: radiation does not explain everything.

Hemorrhagic gastritis is a possible late toxicity outcome after radical radiotherapy but it is nowadays a very rare condition and most likely depends on other clinical factors. We report the case of a 77-year-old woman with a symptomatic solitary extramedullary intra-abdominal plasmacytoma and multiple gastric comorbidities, treated with external beam radiotherapy. Despite the good response to radiotherapy, the patient experienced multiple gastric bleeding a few months later, with the need of multiple treatments for its control. In this paper we will discuss in detail all aspects related to the different causes of hemorrhagic gastritis.

Lipomatous hypertrophy of the interatrial septum: report of two cases where histological examination and surgical intervention were unavoidable.

Lipomatous hypertrophy of the interatrial septum (LHIS) is an increasingly recognized heart condition characterized by fatty deposits in the interatrial septum with sparing of the fossa ovalis. Its distinctive characteristic features by imaging techniques, benign nature, and the fact that most patients remain asymptomatic, has limited the need for histological confirmation and operative intervention in most cases. In this report, we describe two cases of LHIS where cardiac surgical intervention was indispensable: in the first patient, due to the presence of an additional left atrial tumour found out as mixoma and in the second, to relief a superior vena cava obstruction together with bypass grafts for severe coronary artery disease. Histological samples of the interatrial septal lesion were obtained in both cases either because of uncertainty of the diagnosis (Case 1) or to confirm the diagnosis (Case 2).