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1.
Int J Surg ; 2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38518084

ABSTRACT

BACKGROUND: Rectal-sparing approaches for patients with rectal cancer who achieved a complete or major response following neoadjuvant therapy constitute a paradigm of a potential shift in the management of patients with rectal cancer, however their role remains controversial. The aim of this study was to investigate the feasibility of rectal-sparing approaches to preserve the rectum without impairing the outcomes. METHODS: This prospective, multicentre, observational study investigated the outcomes of patients with clinical stage II-III mid-low rectal adenocarcinoma treated with any neoadjuvant therapy, and either transanal local excision or watch-and-wait approach, based on tumor response (major or complete) and patient/surgeon choice. The primary endpoint of the study was rectum preservation at a minimum follow-up of two years. Secondary endpoints were overall, disease-free, local and distant recurrence-free, and stoma-free survival at three years. RESULTS: Of 178 patients enrolled in 16 centres, 112 (62.9%) were managed with local excision and 66 (37.1%) with watch-and-wait. At a median (interquartile range) follow-up of 36.1 (30.6-45.6) months, the rectum was preserved in 144 (80.9%) patients. The 3-year rectum-sparing, overall, disease-free, local recurrence-free, distant recurrence-free survival was 80.6% (95%CI 73.9-85.8), 97.6% (95%CI 93.6-99.1), 90.0% (95%CI 84.3-93.7), 94.7% (95%CI 90.1-97.2), and 94.6% (95%CI 89.9-97.2), respectively. The 3-year stoma-free survival was 95.0% (95%CI 89.5-97.6). The 3-year regrowth-free survival in the watch-and-wait group was 71.8% (95%CI 59.9-81.2). CONCLUSIONS: In rectal cancer patients with major or complete clinical response after neoadjuvant therapy, the rectum can be preserved in about 80% of cases, without compromise the outcomes.

2.
Dig Liver Dis ; 2023 Dec 08.
Article in English | MEDLINE | ID: mdl-38071180

ABSTRACT

BACKGROUND & AIMS: Multiple colorectal adenomas (MCRAs) can result from APC (AFAP) or biallelic MUTYH (MAP) mutations, but most patients are wild type and referred to as non-APC/MUTYH polyposis (NAMP). We aim to examine the risk of colorectal cancer (CRC) and the role of endoscopy in managing patients with MCRAs, with a specific focus on clinical features and genotype. METHODS: Records of MRCAs between 2000 and 2022 were retrospectively analysed. Patients were divided according to the genotype (MAP vs. NAMP) and the number of categorised polyps' burden (group 1: 10-24, group 2: 25-49, and group 3: 50-99 adenomas). Predictors of outcome were CRC-free survival (CRC-FS) and Surgery free-survival (S-FS). RESULTS: 220 patients were enrolled (NAMP n = 178(80.0%)). CRC at diagnosis was more frequent in group 3 (p = 0.01), without significant differences between the genotypes (p = 0.20). At a follow-up of 83(41-164) months, 15(7%) patients developed CRC during surveillance. CRC-FS was not correlated to genotype (p = 0.07) or polyps' number (p = 0.33), while S-FS was similar in MAP and NAMP (p = 0.22) and lower in groups 2 and 3 (p = 0.0001). CONCLUSIONS: MAP and NAMP have the same CRC risk and no difference in treatment. Endoscopic surveillance compared favorably with surgery in avoiding CRC risk, even in patients with more severe colorectal polyposis.

3.
Genes (Basel) ; 14(5)2023 04 27.
Article in English | MEDLINE | ID: mdl-37239344

ABSTRACT

A rhabdoid colorectal tumor (RCT) is a rare cancer with aggressive clinical behavior. Recently, it has been recognized as a distinct disease entity, characterized by genetic alterations in the SMARCB1 and Ciliary Rootlet Coiled-Coil (CROCC). We here investigate the genetic and immunophenotypic profiling of 21 RCTs using immunohistochemistry and next-generation sequencing. Mismatch repair-deficient phenotypes were identified in 60% of RCTs. Similarly, a large proportion of cancers exhibited the combined marker phenotype (CK7-/CK20-/CDX2-) not common to classical adenocarcinoma variants. More than 70% of cases displayed aberrant activation of the mitogen-activated protein kinase (MAPK) pathway with mutations prevalently in BRAF V600E. SMARCB1/INI1 expression was normal in a large majority of lesions. In contrast, ciliogenic markers including CROCC and γ-tubulin were globally altered in tumors. Notably, CROCC and γ-tubulin were observed to colocalize in large cilia found on cancer tissues but not in normal controls. Taken together, our findings indicate that primary ciliogenesis and MAPK pathway activation contribute to the aggressiveness of RCTs and, therefore, may constitute a novel therapeutic target.


Subject(s)
Cilia , Colorectal Neoplasms , Humans , Cilia/genetics , Cilia/metabolism , Proto-Oncogene Proteins B-raf/genetics , Mitogen-Activated Protein Kinases/genetics , Tubulin , Colorectal Neoplasms/pathology , Cytoskeletal Proteins
5.
Pathol Res Pract ; 243: 154366, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36774759

ABSTRACT

BACKGROUND: Approximately 15 % of colorectal adenocarcinomas (CRCs) are characterized by an altered expression of DNA mismatch repair (MMR) proteins (i.e. MMR deficiency [MMRd]). Lymph node ratio (LNR) represents one of the most important prognostic markers in non-advanced CRCs. No significant data are available regarding LNR distribution depending on MMR status. PURPOSE OF THE STUDY: The aim of the present work was to compare pathological and clinical characteristics of MMRd tumors versus MMR proficient (MMRp) cases. Particular attention was paid to how these molecular sub-groups relate to the LNR. MATERIALS AND METHODS: A mono-Institutional series of 1037 consecutive surgically treated stage I-IV CRCs were retrospectively selected and data were obtained from pathological reports. Cases were characterized for MMR/MSI status by means of immunohistochemistry or for microsatellite instability (MSI) analysis. RESULTS: MMRd/MSI tumors (n = 194; 18.7 %) showed significant differences in comparison to MMRp lesions for sex (female prevalence 50.5 % vs 40.7 %; p = 0.013), age (74.2 vs 69.2; p < 0.001), location (right side; p < 0.001), diameter (larger than MMRp; p < 0.001), growth pattern (expansive pattern of growth; p < 0.001), peri- (p = 0.0002) and intra-neoplastic (p = 0.0018) inflammatory infiltrate, presence of perineural invasion (p < 0.001), stage (lower stage at presentation; p < 0.001), grade (higher prevalence of high-grade tumors; p < 0.001), and LNR (lower; p < 0.001). CONCLUSIONS: MMRd/MSI tumors are a distinct molecular CRC subtype characterized by a significantly lower LNR in comparison to MMRp lesions. These data further support the prognostic impact of MMRd/MSI status in early-stage CRCs.


Subject(s)
Adenocarcinoma , Colorectal Neoplasms , Humans , Female , DNA Mismatch Repair , Retrospective Studies , Microsatellite Instability , Colorectal Neoplasms/pathology , Adenocarcinoma/pathology
6.
Cancers (Basel) ; 15(2)2023 Jan 11.
Article in English | MEDLINE | ID: mdl-36672414

ABSTRACT

Local Excision (LE) or Watch and Wait (WW) for patients with complete clinical response or near-complete clinical response after neoadjuvant chemoradiotherapy (nCRT) were proposed to avoid morbidity and impairment of quality of life after rectal resection. The aim of this study is to perform a systematic review of the literature, and to compare rectal-sparing approaches, in terms of rectum-preservation rate, local control, and distant recurrences. A systematic review and meta-analysis were performed of studies published until July 2022 (PROSPERO, registration CRD42022341480), and the quality of evidence was assessed using a GRADE approach. Seven retrospective studies and one prospective trial were included. In six studies, patients were treated with standard long-course nCRT, and in two with Total Neoadjuvant Therapy (TNT). Overall, there were 213 and 188 patients in WW and LE group, respectively, and no difference was found between WW and LE when considering rectum-preservation rate (OR 0.80 95%CI 0.31-2.01, p = 0.63), local disease (OR 1.60 95%CI 0.75-3.42, p = 0.22), locoregional failure (OR 0.85 95%CI 0.20-3.66, p = 0.83) and distant recurrence (OR 0.76 95%CI 0.37-1.55, p = 0.45). Studies directly comparing WW and LE are still lacking, even though no differences between WW and LE in terms of rectum-preservation, local control, and distant recurrences have been found.

7.
Am Surg ; 89(4): 1267-1270, 2023 Apr.
Article in English | MEDLINE | ID: mdl-33605778

ABSTRACT

Brunner's gland hamartoma is a rare duodenal lesion. Resection for benign neoplasms of the duodenum should be considered in case of malignant potential or in case of symptomatic lesions. An accurate preoperative staging is mandatory in order to allow minimally invasive surgical approach, and to avoid under- or overtreatment. Endoscopic ultrasonography (EUS), Computed tomography (CT) scan, Magnetic Resonance Imaging (MRI) and PET/CT are techniques widely used for gastrointestinal tumor staging. We report a case of a 41-year-old female presenting a giant lesion of the second portion of the duodenum. Pathological examination of multiple forceps biopsies was inconclusive for histological characterization of the lesion. After a clinical staging including Esophagusgastroduodenoscopy, EUS, and CT scan, a Hybrid 18FDG PET/MRI was performed to assess the malignant potential of the lesion and the relation between polyp base and Vater's papilla. After multidisciplinary meeting, the patient underwent robotic transduodenal excision. The post-operative course was uneventful, and the patient was discharged on post-operative day 5. Final pathologic report consists in a histologically of Brunner's Glands Hamartoma. This is the first report on the role of 18FDG PET/MRI in staging and planning treatment of bulky low malignant duodenal lesion. An accurate staging with 18FDG PET/MRI could be very useful in the planning the management of duodenal lesion with uncertain malignant potential in order to avoid under- and overtreatment.


Subject(s)
Brunner Glands , Hamartoma , Robotic Surgical Procedures , Female , Humans , Adult , Fluorodeoxyglucose F18 , Positron Emission Tomography Computed Tomography/methods , Positron-Emission Tomography/methods , Magnetic Resonance Imaging/methods , Hamartoma/diagnostic imaging , Hamartoma/surgery , Hamartoma/pathology , Brunner Glands/pathology , Radiopharmaceuticals
8.
Dig Liver Dis ; 55(3): 336-341, 2023 Mar.
Article in English | MEDLINE | ID: mdl-35999134

ABSTRACT

Fecal immunochemical tests (FIT) are among the most commonly used tests for colorectal cancer (CRC) screening programs worldwide. However, no randomised controlled trials have been carried out evaluating the impact of FIT-based screening programs (FIT-progr) on CRC incidence and mortality rates. Italian FIT-progr represent one of the most widespread and established experience worldwide. This paper reviews the evidence on the impact of FIT-progr on CRC incidence, tumor stage at diagnosis, mortality and surgery rates, deriving from Italian routine programs, i.e., outside the research setting. Unfortunately, the application of FIT-progr in Italy can be considered as an unplanned experimental model, due to the differences between Regions, both in health system management and adherence of the target population to the screening programs. The analysis of the manuscripts considered in the review, confirms that FIT-progr are effective in reducing CRC incidence and mortality rates and in improving the rate of endoscopic treatment of early invasive lesions. The review also highlights that FIT-progr are less performing for proximal colon than for distal colon and rectum.


Subject(s)
Colorectal Neoplasms , Early Detection of Cancer , Humans , Incidence , Colorectal Neoplasms/diagnosis , Colonoscopy , Mass Screening , Occult Blood , Italy/epidemiology , Feces
9.
Genes (Basel) ; 15(1)2023 12 27.
Article in English | MEDLINE | ID: mdl-38254934

ABSTRACT

BACKGROUND: Adult pancreatoblastoma (PBL) is a rare pancreatic malignancy, with recent evidence suggesting a possible link to familial adenomatous polyposis (FAP). This study aims to review the latest evidence and explore a possible association between adult PBL and FAP. METHODS: Two independent literature reviews were conducted: (1) on PBL and FAP, and (2) on PBL in the adult population not diagnosed with FAP. RESULTS: Out of 26 articles on PBL and FAP screened, 5 were selected for systematic review, including 1 additional case. We identified eight FAP-related PBL cases, with a median age of 40 (IQR: 34-50). Of these, seven (87%) occurred in adults. We found 65 cases of adult PBL not FAP-related; thus, 7 out of 65 cases (10.7%) of adult PBL reported in the literature are associated with a clinical diagnosis of FAP or were carriers of APC germline pathogenic variants (GPVs). CONCLUSION: Data suggest a non-random association between adult PBL and FAP. Further research is essential to optimise surveillance protocols and develop more effective treatment strategies.


Subject(s)
Adenomatous Polyposis Coli , Pancreatic Neoplasms , Adult , Humans , Adenomatous Polyposis Coli/genetics , Germ-Line Mutation , Pancreatic Neoplasms/epidemiology , Pancreatic Neoplasms/genetics
10.
Genes (Basel) ; 13(11)2022 10 26.
Article in English | MEDLINE | ID: mdl-36360190

ABSTRACT

We describe a patient with constitutional mismatch repair-deficiency (CMMR-D) in whom the syndrome started at age 10 with the development of multiple adenomas in the large bowel. In the successive 25 years, four malignancies developed in different organs (rectum, ileum, duodenum, and lymphoid tissue). The patient had biallelic constitutional pathogenic variants in the PMS2 gene. We speculate that besides the PMS2 genotype, alterations of other genes might have contributed to the development of the complex phenotype. In the nuclear family, both parents carried different PMS2 germline mutations. They appeared in good clinical condition and did not develop polyps or cancer. The index case had a brother who died at age three of lymphoblastic leukemia, and a sister who was affected by sarcoidosis. Tumor tissue showed diffuse DNA microsatellite instability. A complete absence of immunoreactivity was observed for the PMS2 protein both in the tumors and normal tissues. Next-generation sequencing and multiple ligation-dependent probe amplification analyses revealed biallelic PMS2 germline pathogenic variants in the proband (genotype c.[137G>T];[(2174+1_2175-1)_(*160_?)del]), and one of the two variants was present in both parents-c.137G>T in the father and c.(2174+1-2175-1)_(*160_?)del in the mother-as well as c.137G>T in the sister. Moreover, Class 3 variants of MSH2 (c.1787A>G), APC (c.1589T>C), and CHEK2 (c.331G>T) genes were also detected in the proband. In conclusion, the recognition of CMMR-D may sometimes be difficult; however, the possible role of constitutional alterations of other genes in the development of the full-blown phenotype should be investigated in more detail.


Subject(s)
DNA Repair Enzymes , Neoplastic Syndromes, Hereditary , Male , Humans , Mismatch Repair Endonuclease PMS2/genetics , DNA Repair Enzymes/genetics , Adenosine Triphosphatases/genetics , DNA-Binding Proteins/genetics , Neoplastic Syndromes, Hereditary/genetics , Microsatellite Instability
11.
Front Oncol ; 12: 994444, 2022.
Article in English | MEDLINE | ID: mdl-36249024

ABSTRACT

Background: The aim of this study is to evaluate the correlation between body mass index (BMI) and body fat composition (measured with radiological fat parameters (RFP)) and pathological response after neoadjuvant chemoradiotherapy for locally advanced rectal cancer patients. The secondary aim of the study was to assess the role of BMI and RFP on major surgical complications, overall survival (OS), and disease-free survival (DFS). Methods: All patients who underwent surgical resection following nCRT between 2005 and 2017 for mid-low rectal cancer were retrospectively collected. Visceral fat area (VFA), superficial fat area (SFA), visceral/superficial fat area ratio (V/S), perinephric fat thickness (PNF), and waist circumference (WC) were estimated by baseline CT scan. Predictors of pathologic response and postoperative complications were investigated using logistic regression analysis. The correlations between BMI and radiologic fat parameters and survival were investigated using the Kaplan-Meier method and log-rank test. Results: Out of 144 patients included, a complete (TRG1) and major (TRG1+2) pathologic response was reported in 32 (22%) and 60 (45.5%) cases, respectively. A statistically significant correlation between BMI and all the RFP was found. At a median follow-up of 60 (35-103) months, no differences in terms of OS and DFS were found considering BMI and radiologic fat parameters. At univariable analysis, neither BMI nor radiologic fat parameters were predictors of complete or major pathologic response; nevertheless, VFA, V/S>1, and BMI were predictors of postoperative major complications. Conclusions: We found no associations between BMI and body fat composition and pathological response to nCRT, although VFA, V/S, and BMI were predictors of major complications. BMI and RFP are not related to worse long-term OS and DFS.

13.
Dig Liver Dis ; 53(4): 409-417, 2021 04.
Article in English | MEDLINE | ID: mdl-33504457

ABSTRACT

An expert consensus panel convened by the Italian Association for Inherited and Familial Gastrointestinal Tumors (Associazione Italiana per lo Studio della Familiarità ed Ereditarietà dei Tumori Gastrointestinali, AIFEG) reviewed the literature and agreed on a number of position statements regarding the definition and management of polyposis coli without an identified pathogenic mutation on the APC or MUTYH genes, defined in the document as NAMP (non-APC/MUTYH polyposis).


Subject(s)
Adenomatous Polyposis Coli/diagnosis , Adenomatous Polyposis Coli/therapy , Adenomatous Polyposis Coli Protein/genetics , Consensus , DNA Glycosylases/genetics , Germ Cells , Humans , Italy , Societies, Medical
14.
Eur J Surg Oncol ; 46(9): 1613-1619, 2020 09.
Article in English | MEDLINE | ID: mdl-32620405

ABSTRACT

BACKGROUND: The optimal surgical treatment for colonic colorectal carcinoma (CRC) in Lynch Syndrome (LS) and attenuated polyposis coli (A-FAP phenotype) patients is still debated, since there is a high risk of metachronous colonic adenomas and carcinoma after primary surgery. The aim of this study was to compare surgical outcome, functional data, and Quality of Life (QoL) after total colectomy with ileorectal anastomosis (TC-IRA) compared to right (RH) or left hemicolectomy/sigmoidectomy (LH/SI). METHODS: Patients who underwent TC-IRA (ileorectal anastomosis from 8 to 15 cm from the anal verge) for CRC and/or polyposis at our Surgical Department between 2001 and 2017 were included in the study group, and were matched one-to-one by baseline and clinical characteristics with a control group of RH and LH/SI. Morbidity and mortality data were collected (Clavien-Dindo classification). International validated questionnaires were used to investigate QoL and bowel function. RESULTS: Fifty-five patients were enrolled in each group. No differences were found on length of hospital stay, Clavien-Dindo grade III-IV complications and mortality (p > 0.05). TC-IRA showed a longer operative time than RH and LH/SI (p < 0.0001) and a major blood loss than RH (p < 0.0001). Worse bowel function and worse QoL, only for the bowel-related items, were recorded in TC-IRA group. The general QoL was similar among the groups. CONCLUSIONS: TC-IRA and segmental resection have similar morbidity and mortality. The worse bowel function in TC-IRA group does not impact on the general QoL. These data can be useful in the setting of risk-reducing surgery decision in LS and A-FAP patients.


Subject(s)
Adenomatous Polyposis Coli/surgery , Anastomosis, Surgical/methods , Colectomy/methods , Colorectal Neoplasms, Hereditary Nonpolyposis/surgery , Postoperative Complications/epidemiology , Quality of Life , Adenomatous Polyposis Coli/pathology , Adult , Aged , Aged, 80 and over , Blood Loss, Surgical , Colorectal Neoplasms, Hereditary Nonpolyposis/pathology , Female , Humans , Ileum/surgery , Length of Stay , Male , Middle Aged , Mortality , Operative Time , Rectum/surgery , Surgical Wound Infection/epidemiology
15.
J Gastric Cancer ; 20(2): 225-231, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32596005

ABSTRACT

Gastric cancer is a rare condition affecting patients with familial adenomatous polyposis (FAP). The mainstay of treatment is total gastrectomy. Since duodenal cancer is the most common cause of death after total colectomy in FAP, endoscopic surveillance for duodenal cancer is mandatory. Here, we describe the use of an isoperistaltic jejunal loop interposition technique to reconstruct the digestive tract after total gastrectomy in 2 patients with FAP. There were no early or late complications. Both patients are still alive and in good clinical condition. They did not experience weight loss or symptoms of dumping syndrome. Duodenal endoscopic surveillance after this technique was easier than after the classical Roux-en-Y reconstruction. Hence, regular follow-up was possible for both patients.

16.
Dis Colon Rectum ; 63(3): 310-318, 2020 03.
Article in English | MEDLINE | ID: mdl-31842163

ABSTRACT

OBJECTIVE: F-FDG-PET/MRI is a novel hybrid techinque that has been recently introduced in oncological imaging, showing promising results. The aim of this study is to assess the value of whole-body F-FDG-PET/MRI for predicting the pathological stage of locally advanced rectal cancer after preoperative chemoradiotherapy. DESIGN: This was a prospective observational study. SETTINGS: The study was conducted at a tertiary care hospital. PATIENTS: Thirty-six patients with locally advanced rectal cancer (25 male, median age 68.5 years) were prospectively assessed with PET/MRI and thoracoabdominal CT before and after preoperative chemoradiotherapy. Twenty-seven patients underwent low anterior or abdominoperineal resection. Nine patients with a complete clinical response underwent organ-preserving treatment (8 local excision and 1 watch-and-wait approach) with >1-year follow-up. MAIN OUTCOME MEASURES: One radiologist evaluated pelvic MRI and CT. A second radiologist and a nuclear medicine physician jointly assessed PET/MRI. The imaging was compared with histology or follow-up (ypT0 vs T ≥1 and ypN0 vs ypN+ categories). Metastases were confirmed with biopsy or a follow-up CT scan at least at 1 year after preoperative chemoradiotherapy. The sensitivity, specificity, and accuracy values of the imaging techniques were calculated using standard formulas. RESULTS: The accuracy for ypT staging was 89% and 92%, and the accuracy for ypN was 86% and 92% for MRI and PET/MRI. Compared with CT, PET/MRI correctly diagnosed 4 of 5 metastases, but it did not detect a lung metastatic nodule. In 11% of the patients, the PET/MRI changed the treatment strategy. LIMITATIONS: This study is limited by its small sample size. CONCLUSIONS: Although the whole-body PET/MRI was more accurate than the pelvic MRI alone for the prediction of tumor and node response to preoperative chemoradiotherapy, the technique performed worse than CT in detecting small lung metastasis. See Video Abstract at http://links.lww.com/DCR/B108. TOMOGRAFÍA POR EMISIÓN DE POSITRONES DE 18F- FLUORODEOXIGLUCOSA (FDG) / RESONANCIA MAGNÉTICA (TEP/RM) PARA ESTADIFICACIÓN TUMORAL TNM DE CÁNCER DEL RECTO DESPUÉS DE LA QUIMIORRADIOTERAPIA PREOPERATORIA - EXPERIENCIA INICIAL: Evaluar el valor de la tomografía por emisión de positrones de 18F-fluorodeoxiglucosa / resonancia magnética (TEP/RM) para predecir el estadio patológico del cáncer de recto localmente avanzado después de la quimiorradioterapia preoperatoria.Este fue un estudio prospectivo observacional.El estudio se realizó en un hospital de atención terciaria.Treinta y seis pacientes con cáncer rectal localmente avanzado (25 hombres, edad media de 68.5 años) fueron evaluados prospectivamente con TEP/RM y tomografía computarizada (TC) toraco-abdominal antes y después de la quimiorradioterapia preoperatoria. Veintisiete pacientes se sometieron a resección anterior baja o abdominoperineal. Nueve pacientes con una respuesta clínica completa se sometieron a un tratamiento de preservación de órganos (8 escisión local y 1 un enfoque de observar y esperar) con un seguimiento de> 1 año.Un radiólogo evaluó la RM pélvica y la TC. Un segundo radiólogo y un médico de medicina nuclear evaluaron conjuntamente TEP / RM. La imagen se comparó con la histología o el seguimiento (ypT0 vs T ≥1 y ypN0 vs ypN + categorías). Las metástasis se confirmaron con biopsia o una TC de seguimiento al menos 1 año después de la quimiorradioterapia preoperatoria. Los valores de sensibilidad, especificidad y precisión de las técnicas de imagen se calcularon utilizando fórmulas estándar.La precisión para la estadificación ypT fue del 89% y 92%, y la precisión para ypN fue del 86% y 92% para RM y TEP/RM respectivamente. En comparación con la TC, la TEP / RM diagnosticó correctamente 4 de 5 metástasis, pero no detectó un nódulo metastásico pulmonar. En el 11% de los pacientes, la TEP / RM cambió la estrategia de tratamiento.Este estudio está limitado por su pequeño tamaño de muestra.Si bien la TEP / RM de todo el cuerpo fue más precisa que la RM pélvica sola para la predicción de la respuesta tumoral y ganglionar a la quimiorradioterapia preoperatoria, la técnica funcionó peor que la TC para detectar metástasis pulmonares pequeños. Consulte Video Resumen en http://links.lww.com/DCR/B108.


Subject(s)
Chemoradiotherapy , Multimodal Imaging , Rectal Neoplasms/diagnostic imaging , Rectal Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Colectomy , Combined Modality Therapy , Female , Fluorodeoxyglucose F18 , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neoplasm Staging , Positron-Emission Tomography , Preoperative Care , Proctectomy , Prospective Studies , Radiopharmaceuticals , Rectal Neoplasms/pathology , Tomography, X-Ray Computed
17.
Int J Tryptophan Res ; 12: 1178646919890293, 2019.
Article in English | MEDLINE | ID: mdl-31798304

ABSTRACT

Familial adenomatous polyposis (FAP), a common inherited form of colorectal cancer (CRC), causes the development of hundreds to thousands of colonic adenomas in the colorectum beginning in early adolescence. In absence of a prophylactic surgery, FAP patients almost inevitably develop CRC by the age of 40 to 50. The lack of valuable prognostic biomarkers for FAP patients makes it difficult to predict when the progression from adenoma to malignant carcinoma occurs. Decreased tryptophan (TRP) plasma levels and increased indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan hydroxylase 1 (TPH1) enzymatic activities have been associated to tumour progression in CRC. In the present study, we aimed at investigating whether an altered TRP metabolism might also exist in FAP patients. Our results highlighted that plasma levels of TRP and its main catabolites are comparable between FAP patients and healthy subject. On the contrary, FAP patients presented significantly higher TRP levels with respect to high-grade adenoma (ADE) subjects and CRC patients. Obtained data lead us to evaluate IDO1 and TPH1 enzymes activity in the study groups. For both enzymes, it was possible to discriminate correctly between FAP subject and ADE/CRC patients with high sensitivities and specificities. By receiver operating characteristic (ROC) curve analysis, the cut-off values of IDO1 and TPH1 enzymatic activities associated to the presence of an active malignant transformation have been calculated as >38 and >5.5, respectively. When these cut-off values are employed, the area under the curve (AUC) is > 0.8 for both, indicating that TRP metabolism in patients with FAP may be used to monitor and predict the tumorigenic evolution.

18.
Mol Genet Genomic Med ; 7(5): e587, 2019 05.
Article in English | MEDLINE | ID: mdl-30916491

ABSTRACT

BACKGROUND: Inherited epimutations of Mismatch Repair (MMR) genes are responsible for Lynch Syndrome (LS) in a small, but well defined, subset of patients. Methylation of the MSH2 promoter consequent to the deletion of the upstream EPCAM gene is found in about 1%-3% of the LS patients and represents a classical secondary, constitutional and tissue-specific epimutation. Several different EPCAM deletions have been reported worldwide, for the most part representing private variants caused by an Alu-mediated recombination. METHODS: 712 patients with suspected LS were tested for MMR mutation in our Institute. EPCAM deletions were detected by multiplex ligation-dependent probe amplification (MLPA) and then defined by Long-Range polymerase chain reaction (PCR)/Sanger sequencing. A comprehensive molecular characterization of colorectal cancer (CRC) tissues was carried out by immunohistochemistry of MMR proteins, Microsatellite Instability (MSI) assay, methylation specific MLPA and transcript analyses. In addition, somatic deletions and/or variants were investigated by MLPA and next generation sequencing (NGS). RESULTS: An EPCAM deletion was found in five unrelated probands in Italy: variants c.556-490_*8438del and c.858+1193_*5826del are novel; c.859-1430_*2033del and c.859-670_*530del were previously reported. All probands were affected by CRC at young age; tumors showed MSI and abnormal MSH2/MSH6 proteins expression. MSH2 promoter methylation, as well as aberrant in-frame or out-of-frame EPCAM/MSH2 fusion transcripts, were detected in CRCs and normal mucosae. CONCLUSION: An EPCAM deletion was the causative variant in about 2% of our institutional series of 224 LS patients, consistent with previously estimated frequencies. Early age and multiple CRCs was the main clinical feature of this subset of patients.


Subject(s)
Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Epithelial Cell Adhesion Molecule/genetics , Gene Deletion , Gene Frequency , Adult , DNA Methylation , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Female , Humans , Male , Middle Aged , MutS Homolog 2 Protein/genetics , MutS Homolog 2 Protein/metabolism , Phenotype
19.
Eur J Cancer ; 110: 32-41, 2019 03.
Article in English | MEDLINE | ID: mdl-30739838

ABSTRACT

BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) does not achieve effective control of distant metastases. Induction chemotherapy is a promising strategy, and bevacizumab (BV) could improve the results of CRT. 5-Fluorouracil, oxaliplatin and irinotecan (FOLFOXIRI) plus BV is a treatment option in metastatic colorectal cancer. We evaluate feasibility and efficacy of neoadjuvant treatment comprising induction FOLFOXIRI plus BV followed by CRT with fluoropyrimidines plus BV. METHODS: In this phase II single-arm trial, patients node-positive or clinical T4 or high-risk T3 LARC underwent 6 cycles of induction FOLFOXIRI plus BV, followed by CRT (50.4 Gy plus concomitant capecitabine) and BV (5 mg/kg on days 1, 15 and 28). Surgery was planned 8 weeks after completion of CRT. Primary end-point was 2-year disease-free survival (DFS). RESULTS: We enrolled 49 patients: All but one (withdrewing consent after enrolment) were included in the per-protocol analyses. The study met its primary end-point: 36 patients were free of recurrence at 2 years (2-y DFS: 80.45%, 95% confidence interval [CI]: 78.79-82.10). Forty-four patients underwent surgery; pathologic complete response rate was 36.4%. Forty-six patients completed induction: neutropenia (41.6%) and diarrhoea (12.5%) were main G3/4 toxicities. Forty-five patients received CRT, but the protocol was amended and the capecitabine schedule during CRT was slightly modified after 13 patients due to the incidence of G3 hand-foot syndrome and proctitis (23.1%). After amendment, no severe events during CRT were reported. CONCLUSIONS: FOLFOXIRI plus BV followed by CRT plus BV is feasible and active. Results in terms of DFS suggest that this strategy may improve distant disease control in LARC.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Rectal Neoplasms/therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bevacizumab/administration & dosage , Bevacizumab/adverse effects , Camptothecin/administration & dosage , Camptothecin/adverse effects , Camptothecin/analogs & derivatives , Chemoradiotherapy/methods , Chemoradiotherapy/mortality , Disease-Free Survival , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Leucovorin/administration & dosage , Leucovorin/adverse effects , Male , Middle Aged , Neoadjuvant Therapy/methods , Neoadjuvant Therapy/mortality , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/adverse effects , Rectal Neoplasms/mortality , Treatment Outcome
20.
Oncologist ; 24(2): e77-e79, 2019 02.
Article in English | MEDLINE | ID: mdl-30120156

ABSTRACT

BACKGROUND: The prognostic value of primary tumor location (PTL) in patients with metastatic colorectal cancer (mCRC) was reported by recent analyses in RAS wild-type patients. Here, we investigated the prognostic value of PTL in RAS mutated mCRC patients. MATERIALS AND METHODS: PTL was defined as left or right if distal or proximal to the splenic flexure. Primary endpoint was overall survival (OS) according to PTL. Subgroup analyses were conducted according to time to metastases and RAS mutation subtypes. RESULTS: Five hundred sixty-four patients were included. Left- and right-sided cases were 65% and 35%, respectively. No difference in OS was detected according to PTL (hazard ratio [HR] = 0.99, p = .964). No difference in OS was observed in right versus left when looking at synchronous (HR 0.92, p = .557) or metachronous (HR 1.07, p = .807) patients. CONCLUSION: No OS difference was detected in RAS mutated mCRC. Molecular and clinical features able to improve prognosis and treatment strategies in this setting are needed.


Subject(s)
Colorectal Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Mutation , Prognosis , Young Adult
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