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PURPOSE: Colorectal adenomatous polyposis is characterized by the onset of tens to thousands of adenomas in the colorectal epithelium and, if not treated, leads to a lifetime increased risk of developing colorectal cancer compared to the general population. Thus, prophylactic surgery is recommended. This study aims to investigate the quality of life of colorectal adenomatous polyposis patients following prophylactic surgery and indirectly compares these findings with those of healthy adults of the normative sample. METHODS: All patients who underwent prophylactic surgery for polyposis and were in follow-up at the hereditary digestive tract tumors outpatient department of our institute were eligible for the study. The Short Form-36 questionnaire and 21 ad hoc items were used at the time of clinical evaluation. RESULTS: A total of 102 patients were enrolled. For the SF-36 domains, mean values ranged from 64.18 for vitality to 88.49 for physical functioning, with the highest variability for role-physical limitations; the minimum value of functioning was reached for role-physical limitations, role-emotional limitations, and social functioning. The maximum value of functioning was reached for role-emotional limitations (73.96%) and role-physical limitations (60.42%). In total, 48.96% and 90.63% of patients reported no fecal or urinary incontinence episodes, respectively; 69.79% of patients did not have problems in work/school resumption or the personal sexual sphere. CONCLUSION: Quality of life following prophylactic surgery for these patients seems to be good when indirectly compared to HP-normative samples'. Young adult patients appear to quickly manage and adapt to changes in bowel functioning. A minority of patients may experience social and sexual issues.
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Poliposis Adenomatosa del Colon , Neoplasias Colorrectales , Proctocolectomía Restauradora , Humanos , Calidad de Vida , Poliposis Adenomatosa del Colon/cirugía , Poliposis Adenomatosa del Colon/patología , Neoplasias Colorrectales/prevención & control , Neoplasias Colorrectales/cirugía , ColectomíaRESUMEN
PURPOSE: The coronavirus 2019 (COVID-19) pandemic has had profound consequences also for non-infected patients. This study aimed to evaluate the impact of the pandemic on the quality of life of a population with hereditary gastrointestinal cancer predisposition syndromes and on the surveillance/oncological care program of patients enrolled in a dedicated registry. METHODS: The study was conducted by means of an online self-report survey during the first Italian national lockdown. The survey comprised four sections: demographics; perception/knowledge of COVID-19; impact of the COVID-19 pandemic on surveillance and cancer care; health status (SF-12 questionnaire). RESULTS: 211 complete questionnaires were considered. 25.12% of respondents reported being not at all frightened by COVID-19, 63.98% felt "not at all" or "a little" more fragile than the healthy general population, and 66.82% felt the coronavirus to be no more dangerous to them than the healthy general population. 88.15% of respondents felt protected knowing they were monitored by a team of dedicated professionals. CONCLUSION: Patients with hereditary gastrointestinal cancer predisposition syndromes reported experiencing less fear related to COVID-19 than the healthy general population. The study results suggest that being enrolled in a dedicated registry can reassure patients, especially during health crises.
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COVID-19 , Neoplasias Colorrectales , COVID-19/epidemiología , Control de Enfermedades Transmisibles , Humanos , Pandemias , Calidad de Vida/psicología , Sistema de Registros , SARS-CoV-2 , Encuestas y Cuestionarios , SíndromeRESUMEN
INTRODUCTION: Mutations of the APC (adenomatous polyposis coli) gene correlate mainly with familial adenomatous polyposis (FAP), but can occasionally be pathogenic for medulloblastoma (MBL) wingless-related integration site (WNT) subtype, the course of which has only recently been described. METHODS: We retrieved all patients with documented germline APC mutations and a diagnosis of MBL to examine their outcome, late effects of treatment, and further oncological events. RESULTS: Between 2007 and 2016, we treated six patients, all with a pathogenic APC variant mutation and all with MBL, classic histotype. None had metastatic disease. All patients were in complete remission a median 65 months after treatment with craniospinal irradiation at 23.4 Gy, plus a boost on the posterior fossa/tumor bed up to 54 Gy, followed by cisplatin/carboplatin, lomustine, and vincristine for a maximum of eight courses. Five of six diagnostic revised MRI were suggestive of the WNT molecular subgroup typical aspects. Methylation profile score (in two cases) and copy number variation analysis (chromosome 6 deletion in two cases) performed on four of six retrieved samples confirmed WNT molecular subgroup. Four out of six patients had a positive family history of FAP, while gastrointestinal symptoms prompted its identification in the other two cases. Four patients developed other tumors (desmoid, MELTUMP, melanoma, pancreatoblastoma, thyroid Tir3) from 5 to 7 years after MBL. DISCUSSION: Our data confirm a good prognosis for patients with MBL associated with FAP. Patients' secondary tumors may or may not be related to their syndrome or treatment, but warrant adequate attention when planning shared guidelines for these patients.
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Poliposis Adenomatosa del Colon/epidemiología , Neoplasias Cerebelosas/epidemiología , Meduloblastoma/epidemiología , Calidad de Vida , Poliposis Adenomatosa del Colon/complicaciones , Poliposis Adenomatosa del Colon/diagnóstico , Poliposis Adenomatosa del Colon/terapia , Adolescente , Adulto , Neoplasias Cerebelosas/complicaciones , Neoplasias Cerebelosas/diagnóstico , Neoplasias Cerebelosas/terapia , Niño , Manejo de la Enfermedad , Femenino , Humanos , Masculino , Meduloblastoma/complicaciones , Meduloblastoma/diagnóstico , Meduloblastoma/terapia , Linaje , Pronóstico , Adulto JovenRESUMEN
BACKGROUND: Rhabdomyosarcoma (RMS), an aggressive soft tissue sarcoma of the skeletal muscle generally affecting children and adolescents, shows extensive heterogeneity in histology, site and age of onset, clinical course, and prognosis. Tumorigenesis of RMS is multifactorial and genetic predisposition together with the family history of cancer may provide critical information to enhance the current knowledge and foster genetic counseling and testing. METHODS: In our study, we evaluated the possible correlation of oncological family history with clinical outcomes in a cohort of RMS 512 patients and treated at the Pediatric Oncology Unit of our Institute. Family history was retrospectively collected from the specific ad hoc form available in medical records and filled in through an interview with the patients' parents at the time of RMS diagnosis. RESULTS: While our series did not show a specific association between oncological family history and clinical variables, we observed an association with survival probabilities: among patients with a history of cancer-affected first-degree relatives at the time of the diagnosis, all children with alveolar RMS (ARMS) died of disease. CONCLUSION: Our study not only reports an interesting and not previously described association between a poor clinical outcome and ARMS in patients with young cancer-affected relatives, but also stimulates the discussion on oncological family history in RMS, to improve the clinical management of these young patients and their families.
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BACKGROUND: APC gene pathogenic variants are characterized by a lifetime risk of nearly 100% to develop a colorectal carcinoma. International guidelines suggest a prophylactic surgery in the second decade. METHODS: A descriptive analysis was performed evaluating a surgical series of adolescent patients with familial adenomatous polyposis (FAP) enrolled in the prospectively maintained hereditary polyposis registry. RESULTS: Thirty-eight adolescent patients (median age 16 years; range, 7-19) underwent laparoscopic prophylactic surgery. APC gene pathogenic variants were detected in all patients, and six patients were proband. No patients were converted to open surgery. Median postoperative stay was five days (4-16). Early postoperative complications were one dural puncture and one anastomotic leakage. Regarding late complications, we observed one patient having small bowel obstruction 56 months after surgery. Pathological reports showed one patient with pTis adenocarcinoma in two separate sites; 33 patients with low-grade dysplasia, four with high-grade dysplasia. One patient developed a desmoid tumor 37 months after surgery. After a median follow-up of 40.5 months, no patients died or had a second abdominal surgery because of cancer in rectal stump. CONCLUSIONS: Rectal sparing surgery was the first choice in the major respect of patients' quality of life. Laparoscopic prophylactic surgery for FAP is well accepted from adolescents. It represents a safe option due to the low incidence of post-surgical desmoids and quick postoperative recovery.
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Adenocarcinoma/cirugía , Poliposis Adenomatosa del Colon/cirugía , Laparoscopía/métodos , Complicaciones Posoperatorias , Calidad de Vida , Adenocarcinoma/patología , Poliposis Adenomatosa del Colon/patología , Adolescente , Adulto , Niño , Femenino , Estudios de Seguimiento , Humanos , Masculino , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Risk factors for metachronous colorectal cancer (mCRC) in Lynch Syndrome (LS) patients are essential for colorectal cancer (CRC) treatment strategy to perform not only a curative but also preventive surgery. The aim of this study was to evaluate the risk factors for mCRC development in LS patients to define the patient subset that may benefit an extended curative and preventive surgical resection. METHODS: Patient's clinical history, oncological, molecular and follow-up were collected retrospectively from the Hereditary Digestive Tumors Registry at the National Cancer Institute of Milan. The age-related cumulative risk of mCRC was calculated using the Kaplan-Meier method. Factors significantly associated with mCRC were analyzed with a Cox regression model. Overall and specific competitive risks were also calculated. RESULTS: In a total of 1346 CRC patients, 159 (11.8%) developed a mCRC after a mean follow-up of 138 months from the primary tumor. The independent risk factors reported by a multivariate analysis were: pathogenetic variants in MLH1 and MSH2 (HR 2.96 and 1.91, respectively) and history of colorectal adenomas (HR 1.54); whereas female sex and extended surgery were protective (HR 0.59 and 0.79, respectively). CONCLUSIONS: Among a high-risk population for CRC, in particular LS, an extended surgery may be considered in CRC patients with specific risk factors (MLH1 or MSH2 germline pathogenic variants, history of colorectal adenomas) to reduce the risk of mCRC development.
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Neoplasias Colorrectales Hereditarias sin Poliposis/patología , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Neoplasias Primarias Secundarias/patología , Adulto , Anciano , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Homólogo 1 de la Proteína MutL/genética , Proteína 2 Homóloga a MutS/genética , Neoplasias Primarias Secundarias/genética , Neoplasias Primarias Secundarias/mortalidad , Sistema de Registros , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Creative spirit and art are used as part of the Youth Project in Milan, a program dedicated to adolescents and young adults (AYA) with cancer. The "Summer is you" music project involved 45 patients (15-26 years old): with professional help, the patients wrote music and lyrics, sang their song, and recorded a video clip, sharing with us not only their hopes and fears, but also their romantic encounters and their urge to travel (https://youtu.be/Q5FSCMUVg0E). This project exploited the power of music to bring young people with cancer together in a novel form of support that can complement the more conventional psychological approaches.
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Esperanza , Musicoterapia/métodos , Música/psicología , Neoplasias/psicología , Adolescente , Adulto , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
Cutaneous melanoma is rare in children, but has greater incidence in adolescents and young adults (AYAs). Diagnosis may be challenging due to its rarity in these age groups. Few studies have specifically addressed the topic of AYA melanoma. Though young-age melanoma may have particular biological characteristics, available data suggest that its clinical history is similar to that of adults. However, advances in treatment of adult melanoma have not been reflected in the treatment of AYAs. There is no standard treatment, and access to clinical trials is difficult for AYAs. Further efforts are needed to overcome these issues by improving cooperation with experts on adult melanoma.
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Melanoma , Neoplasias Cutáneas , Adolescente , Femenino , Humanos , Masculino , Adulto Joven , Melanoma Cutáneo MalignoRESUMEN
BACKGROUND: Gastrointestinal (GI) carcinomas are very rare in the pediatric and adolescent age range. We report the clinical features, treatment, and outcome of a series of children and adolescents with GI carcinoma prospectively registered in the Italian Tumori Rari in Età Pediatrica (TREP) project. METHODS: The TREP project developed diagnostic and therapeutic guidelines based on recommendations currently in use for adults. Clinical data were centrally registered and reviewed. RESULTS: Fifteen patients were registered over the years 2000-2016. Most of the tumors were colorectal carcinomas (12 cases). All but one patient had advanced-stage disease (American Joint Committee on Cancer stages III-IV), and the majority of patients had aggressive histological subtypes, i.e. poorly differentiated (G3) (five patients), mucinous (four patients), and signet ring (two patients) adenocarcinomas. Surgery was performed in 13 of 15 patients, and was radical in nine of 13 patients. Only one patient received postoperative radiotherapy. All patients received chemotherapy, with the addition of bevacizumab in two cases. Nine patients were still alive at the time of the present report, but two of them had only just completed their treatment program and one patient is still on treatment. Six patients died due to disease progression. CONCLUSIONS: This prospective report on pediatric GI tract carcinomas confirms the rarity and biological aggressiveness of these diseases in pediatric and adolescent age. Further prospective studies are needed to explore the distinct biology of tumor in this age group in order to find new therapeutic targeted agents.
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Neoplasias Gastrointestinales/diagnóstico , Neoplasias Gastrointestinales/terapia , Adolescente , Niño , Femenino , Neoplasias Gastrointestinales/mortalidad , Neoplasias Gastrointestinales/patología , Humanos , Masculino , Estudios ProspectivosRESUMEN
Unrestrained activation of the proteolytic systems in anastomotic tissue during repair has been implicated in the pathogenesis of anastomotic leakage. We hypothesized that this mechanism may promote an up-regulation of the urokinase-type plasminogen activator system and a spillover of soluble urokinase-type plasminogen activator receptor (suPAR) into blood. In this retrospective analysis patients with anastomotic leakage were compared with a group of matched uncomplicated patients. Anastomotic leakage complicated patients had significantly higher suPAR (p = 0.04) levels until day 3 after surgery. The area under the receiver-operating characteristic (ROC) for suPAR was higher than that CRP (0.874 vs. 0.836). Their analysis suggests the possible use of suPAR as serum marker to characterize the persistent inflammatory response that lead to tissue damage and surgical complication.
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Fuga Anastomótica/sangre , Mediadores de Inflamación/sangre , Inflamación/sangre , Inflamación/patología , Complicaciones Posoperatorias/sangre , Receptores del Activador de Plasminógeno Tipo Uroquinasa/sangre , Biomarcadores/sangre , Femenino , Humanos , Masculino , Valor Predictivo de las Pruebas , Curva ROC , Estudios Retrospectivos , Regulación hacia ArribaAsunto(s)
Arteterapia/métodos , COVID-19 , Neoplasias/psicología , Fotograbar , Adolescente , Adulto , Femenino , Humanos , Masculino , SARS-CoV-2 , Adulto JovenRESUMEN
INTRODUCTION: APC-associated polyposis is a rare hereditary disorder characterized by the development of multiple adenomas in the digestive tract. Individuals with APC-associated polyposis need to be managed by specialized multidisciplinary teams in dedicated centers. AREAS COVERED: The study aimed to review the literature on Familial adenomatous polyposis (FAP) to provide an update on diagnostic and surgical management while focusing on strategies to minimize the risk of desmoid-type fibromatosis, cancer in anorectal remnant, and postoperative complications. FAP individuals require a comprehensive approach that includes diagnosis, surveillance, preventive surgery, and addressing specific extracolonic concerns such as duodenal and desmoid tumors. Management should be personalized considering all factors: genotype, phenotype, and personal needs. Total colectomy and ileo-rectal anastomosis have been shown to yield superior QoL results when compared to Restorative Procto colectomy and ileopouch-anal anastomosis with acceptable oncological risk of developing cancer in the rectal stump if patients rigorously adhere to lifelong endoscopic surveillance. Additionally, a low-inflammatory diet may prevent adenomas and cancer by modulating systemic and tissue inflammatory indices. EXPERT OPINION: FAP management requires a multidisciplinary and personalized approach. Integrating genetic advances, innovative surveillance techniques, and emerging therapeutic modalities will contribute to improving outcomes and quality of life for FAP individuals.
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Poliposis Adenomatosa del Colon , Colectomía , Calidad de Vida , Humanos , Poliposis Adenomatosa del Colon/terapia , Poliposis Adenomatosa del Colon/cirugía , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Grupo de Atención al Paciente , Medicina de Precisión , Fenotipo , Genotipo , Fibromatosis Agresiva/terapia , Fibromatosis Agresiva/patologíaRESUMEN
Lynch Syndrome is an autosomal dominant cancer predisposition syndrome caused by germline pathogenic variants or epimutation in one of the DNA mismatch repair genes. De novo pathogenic variants in mismatch repair genes have been described as a rare event in Lynch Syndrome (1-5%), although the prevalence of de novo pathogenic variants in Lynch Syndrome is probably underestimated. The de novo pathogenic variant was identified in a 26-year-old woman diagnosed with an adenocarcinoma of the caecum with mismatch repair protein deficiency at immunohistochemistry and a synchronous neuroendocrine tumor of the appendix with normal expression of mismatch repair proteins. DNA testing revealed deletion of exon 6 of the MLH1 gene. It appeared to be a de novo event, as the deletion was not detected in the patient's parents. The presence of a mosaicism in the patient was excluded and haplotype analysis demonstrated the paternal origin of the chromosome harboring the deletion. The de novo deletion probably originated either from a very early postzygotic or a single prezygotic mutational event, or from a gonadal mosaicism. In conclusion, the identification of de novo pathogenic variants is crucial to allow proper genetic counseling and appropriate management of the patient's family.
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Neoplasias Colorrectales Hereditarias sin Poliposis , Femenino , Humanos , Adulto , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Mutación de Línea Germinal , Mutación , Asesoramiento Genético , Células Germinativas/patología , Homólogo 1 de la Proteína MutL/genética , Reparación de la Incompatibilidad de ADNRESUMEN
Lynch syndrome (LS) is an inherited condition characterized by an increased risk of developing cancer, in particular colorectal cancer (CRC). Microsatellite instability (MSI) is the main feature of (pre)cancerous lesions occurring in LS patients. Close endoscopic surveillance is the only option available to reduce CRC morbidity and mortality. However, it may fail to intercept interval cancers and patients' compliance to such an invasive procedure may decrease over the years. The development of a minimally invasive test able to detect (pre)cancerous colorectal lesions, could thus help tailor surveillance programs in LS patients. Taking advantage of an endoscopic surveillance program, we retrospectively assessed the instability of five microsatellites (BAT26, BAT25, NR24, NR21, and Mono27) in liquid biopsies collected at baseline and possibly at two further endoscopic rounds. For this purpose, we tested a new multiplex drop-off digital polymerase chain reaction (dPCR) assay, reaching mutant allele frequencies (MAFs) as low as 0.01%. Overall, 78 plasma samples at the three time-points from 18 patients with baseline (pre)cancerous lesions and 18 controls were available for molecular analysis. At baseline, the MAFs of BAT26, BAT25 and NR24 were significantly higher in samples of patients with lesions but did not differ with respect to the grade of dysplasia or any other clinico-pathological characteristics. When all markers were combined to determine MSI in blood, this test was able to discriminate lesion-bearing patients with an AUC of 0.80 (95%CI: 0.66; 0.94).
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Neoplasias Colorrectales Hereditarias sin Poliposis , Inestabilidad de Microsatélites , Humanos , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Neoplasias Colorrectales Hereditarias sin Poliposis/patología , Biopsia Líquida/métodos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Adulto , Estudios Retrospectivos , Lesiones Precancerosas/genética , Lesiones Precancerosas/patología , Lesiones Precancerosas/diagnóstico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/diagnóstico , Biomarcadores de Tumor/genéticaRESUMEN
BACKGROUND: Dietary interventions have been proposed as therapeutic approaches for several diseases, including cancer. A low-inflammatory Mediterranean dietary intervention, conducted as a pilot study in subjects with Familial Adenomatous Polyposis (FAP), reduced markers of local and systemic inflammation. We aim to determine whether this diet may modulate faecal microRNA (miRNA) and gene expression in the gut. METHODS: Changes in the faecal miRNome were evaluated by small RNA sequencing at baseline (T0), after the three-month intervention (T1), and after an additional three months (T2). Changes in the transcriptome of healthy rectal mucosa and adenomas were evaluated by RNA sequencing at T0 and T2. The identification of validated miRNA-gene interactions and functional analysis of miRNA targets were performed using in silico approaches. RESULTS: Twenty-seven subjects were included in this study. It was observed that the diet modulated 29 faecal miRNAs (p < 0.01; |log2 Fold Change|>1), and this modulation persisted for three months after the intervention. Levels of miR-3612-3p and miR-941 correlated with the adherence to the diet, miR-3670 and miR-4252-5p with faecal calprotectin, and miR-3670 and miR-6867 with serum calprotectin. Seventy genes were differentially expressed between adenoma and normal tissue, and most were different before the dietary intervention but reached similar levels after the diet. Functional enrichment analysis identified the proinflammatory ERK1/2, cell cycle regulation, and nutrient response pathways as commonly regulated by the modulated miRNAs and genes. CONCLUSIONS: Faecal miRNAs modulated by the dietary intervention target genes that participate in inflammation. Changes in levels of miRNAs and genes with oncogenic and tumour suppressor functions further support the potential cancer-preventive effect of the low-inflammatory Mediterranean diet. CLINICAL TRIAL NUMBER REGISTRATION: NCT04552405, Registered in ClinicalTrials.gov.
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MicroARNs , Neoplasias , Humanos , Inflamación/genética , Inflamación/prevención & control , Complejo de Antígeno L1 de Leucocito , MicroARNs/genética , Proyectos PilotoRESUMEN
INTRODUCTION: Colorectal carcinoma (CRC) is one of the most common tumors in adult, but is extremely rare in children. In childhood, CRC often presents unfavorable aggressive histotypes, advanced clinical stage at onset and a worse prognosis. Pediatric CRC series are limited and include few patients, therefore information about treatment strategy and pharmacotherapy is scarce. For this reason, management of these patients represents a real challenge for pediatric oncologists. AREAS COVERED: The authors provide an overview of the general features and management strategies of pediatric CRC with specific attention to systemic treatment. Literature data regarding pharmacotherapy in published pediatric series are summarized and analyzed in detail, according to adult treatment standards. EXPERT OPINION: In the absence of specific recommendations for pediatric CRC, the general therapeutic strategy should follow the same principles as for adults and should be the result of a multidisciplinary discussion. Patient access to optimal treatment is difficult due to the lack of new drugs approved for the pediatric age group and non-availability of clinical trials. Collaboration between pediatric and adult oncologists is considered crucial in order to overcome these issues and find solutions to increase knowledge and improve the outcome of such a rare disease in children.
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Neoplasias Colorrectales , Adulto , Humanos , Niño , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , PronósticoRESUMEN
This short piece describes a new project developed by the adolescent patients with cancer involved in the Youth Project at the Istituto Nazionale dei Tumori in Milan, Italy. This is a scheme dedicated to young cancer patients with the dual aim of optimizing medical aspects of their care and promoting a holistic approach to their needs. "I was only sixteen" is a ballad, written in English by the patients, that became a song with the help of professional musicians (and among them international star Tony Hadley, former frontman of Spandau Ballet). This song sounds like hymn to life for teenagers with cancer in the world. It emphasizes again the value of giving young patients novel creative ways to express themselves.
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Vascular cyclooxygenase (COX)-2-dependent prostacyclin (PGI(2)) may affect angiogenesis by preventing endothelial activation and platelet release of angiogenic factors present in platelet α-granules. Thus, a profound inhibition of COX-2-dependent PGI(2) might be associated with changes in circulating markers of angiogenesis. We aimed to address this issue by performing a clinical study with celecoxib in familial adenomatous polyposis (FAP). In nine patients with FAP and healthy controls, pair-matched for gender and age, we compared systemic biosynthesis of PGI(2), thromboxane (TX) A(2), and prostaglandin (PG) E(2), assessing their urinary enzymatic metabolites, 2,3-dinor-6-keto PGF(1α) (PGI-M), 11-dehydro-TXB(2) (TX-M), and 11-α-hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (PGE-M), respectively. The impact of celecoxib (400 mg b.i.d. for 7 days) on prostanoid biosynthesis and 14 circulating biomarkers of angiogenesis was evaluated in FAP. Intestinal tumorigenesis was associated with enhanced urinary TX-M levels, but unaffected by celecoxib, suggesting the involvement of a COX-1-dependent pathway, presumably from platelets. This was supported by the finding that in cocultures of a human colon adenocarcinoma cell line (HT-29) and platelets enhanced TXA(2) generation was almost completely inhibited by pretreatment of platelets with aspirin, a preferential inhibitor of COX-1. In FAP, celecoxib profoundly suppressed PGE(2) and PGI(2) biosynthesis that was associated with a significant increase in circulating levels of most proangiogenesis proteins but also the antiangiogenic tissue inhibitor of metalloproteinase 2. Urinary PGI-M, but not PGE-M, was negatively correlated with circulating levels of fibroblast growth factor 2 and angiogenin. In conclusion, inhibition of tumor COX-2-dependent PGE(2) by celecoxib may reduce tumor progression. However, the coincident depression of vascular PGI(2), in a context of enhanced TXA(2) biosynthesis, may modulate the attendant angiogenesis, contributing to variability in the chemopreventive efficacy of COX-2 inhibitors such as celecoxib.