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Biomedical subjects

C Castoro

Publications and source records attributed to C Castoro.

18 recordsLinked to original sources

The role of circulating tumor DNA (ctDNA) to detect minimal residual disease in locally advanced gastroesophageal carcinoma: the BUTTERFLY study.

BACKGROUND: Despite advances in perioperative and neoadjuvant strategies, patients with locally advanced gastroesophageal cancers remain at high risk of recurrence after curative intent treatment. No validated biomarkers are available to detect minimal residual disease (MRD) or to guide post-operative risk-adapted management. Circulating tumor DNA (ctDNA) has emerged as a noninvasive tool for disease monitoring; single-parameter or tumor-informed assays, however, may lack sensitivity in low-tumor burden settings. Multimodal, tumor-agnostic approaches may overcome these limitations. METHODS: The BUTTERFLY study is a prospective, multicenter observational study enrolling patients with stage II-III gastric, gastroesophageal junction, or esophageal cancer treated with perioperative chemotherapy or neoadjuvant chemoradiotherapy followed by surgery. It evaluates the diagnostic performance and prognostic value of an academic, tumor-agnostic, multimodal ctDNA assay for MRD detection and prognostic stratification. Serial plasma samples are collected from baseline through post-operative follow-up and at relapse. Cell-free DNA is analyzed using the Agnostic Liquid Biopsy Multimodal Advancement (ALMA) platform, integrating tumor fraction estimation, somatic copy number alterations, fragmentomic features, single-nucleotide variants, and whole-genome methylation profiling. Multimodal features are combined with clinical variables using machine learning-based models to enhance MRD detection and relapse risk stratification. The primary endpoint includes sensitivity and specificity of ALMA-defined ctDNA/MRD status at the 4-8 weeks after surgery landmark, whereas secondary endpoints assess diagnostic performance at other time points and associations between ctDNA status and dynamics with disease-free survival, overall survival, treatment response, and lead time to recurrence. FUTURE PERSPECTIVES: If validated, this tumor-agnostic, multimodal ctDNA approach may enable earlier molecular relapse detection and support personalized post-operative management strategies.

circulating tumor DNA (ctDNA)

Tumor-associated trypsin inhibitor (TATI) in primary esophageal carcinoma.

Esophageal carcinoma has a catastrophic clinical course with a very low 5 year survival rate of 5%. A circulating tumor marker with good specificity and sensitivity would be useful in the management strategy of the disease. So far, no tumor marker effective in esophageal carcinoma has been identified. Preliminary reports suggest satisfactory positivity rates of tumor-associated trypsin inhibitor (TATI) in esophageal carcinoma. We measured TATI levels in 71 patients with primary squamous cell esophageal carcinoma as well as in 30 tissue samples from both carcinoma and normal esophageal mucosa. Detectable TATI levels were not found in tumor tissue samples. The marker showed significantly higher serum levels in patients than in controls, with an overall positivity rate of 28%. TATI levels were significantly lower in patients with a high number of tumor-positive lymph nodes. No relationship was found between TATI and several other clinical and pathological parameters. High TATI levels correlated with a lower probability of overall survival as well as in cases without clinical evidence of lymph node metastases. TATI did not show any relationship with CEA, TPA, ferritin or SCC. The results of the present study suggest that TATI shows a satisfactory positivity rate in esophageal carcinoma, and TATI levels are related to local disease spread and prognosis.

Biomarkers, Tumor

[Advanced carcinoma of the thoracic esophagus: CT, MR, and echo-endoscopy in the staging after chemotherapy].

Thirteen patients affected with advanced epidermoid carcinoma of the thoracic esophagus were examined by means of CT, MR and endoscopic US (EUS) before and after chemotherapy. Eleven patients underwent esophagectomy and esophagogastroplasty. An intraesophageal prosthesis was positioned in 2 patients since chemotherapy had not modified tumour stage. Post-chemotherapy CT, MR and EUS parameters were compared with the corresponding pathologic findings. As for MR imaging, post-chemotherapy signal intensity variations in T1 and T2 sequences were also evaluated. MR imaging was more accurate than CT in depicting the involvement of mediastinal fatty layers, the relationships between mass and cardiovascular structures, and the cellularity. CT and MR exhibited limitations in identifying metastatic mediastinal lymph nodes, in which case EUS proved to be the most accurate technique. Both CT and MR failed to satisfactorily assess the infiltration of tracheobronchial tree, which was best demonstrated by endoscopy.

Adult

Surgical treatment of carcinoma of the gastric cardia.

The ideal surgical treatment for adenocarcinoma of the gastric cardia is still controversial. In 189 consecutive patients who underwent resection, 127 esophagogastric resections and 62 total gastrectomies plus esophageal resection were performed. Short- and long-term results of the two surgical procedures were compared in order to define the specific indications for each. Abdominal nodes were metastatic in 73.5% of the cases, and mediastinal nodes in 29.1% of the patients who were also approached through the thorax. Neoplastic permeation of the esophageal resection margin occurred in 3.2% of the patients. No positive resection margins were found in the cases in whom 10 or more cm. of uninvolved esophagus were resected. The superiority of the laparotomy and right thoracotomy approach was thus evident in terms of oncologic radicality. Anastomotic leakage occurred in 8.7% of esophagogastric resection, and in 6.5% of total gastrectomy plus esophageal resection, patients. No correlation between the stage of the tumor or the neoplastic permeation of the section margin and the incidence of anastomotic leakage was found. Operative mortality was 3.9% after esophagogastric resection, and 6.5% after total gastrectomy plus esophageal resection; this may suggest that esophagogastric resection is the procedure of choice in poor risk and elderly patients. After curative resection, locoregional or systemic neoplastic recurrence was observed in 15.0% of the cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma

[Cancer of the hypopharynx and cervical esophagus].

Between 1975 and 1988 we observed 169 patients with carcinoma of the cervical esophagus, 85 with a carcinoma involving the hypopharynx and the cervical esophagus, and 27 patients with a carcinoma of the cervical esophageal region arising after laryngectomy for laryngeal cancer. The mean age was 57.5 years (range 41-73). 167 patients underwent surgical exploration (operability rate 59.5%) and in 152 cases the tumor was resected (resectability rate 91.1%). The resection was complete in 129 patients (84.5%) and palliative in 23 (14.5%). In 33 cases a segmental laryngo-pharyngo-cervical esophagectomy with free intestinal loop transplantation was performed with an operative mortality of 6.1%. 101 patients underwent total laryngo-pharyngo esophagectomy and the gastrointestinal tract was reconstructed by means of pharyngo-gastrostomy and pharyngo-colostomy in 85 and 16 cases, with an operative mortality of 12.9% and 18.3%, respectively. Total esophagectomy without laryngectomy was performed in 18 patients with a carcinoma of the distal cervical esophagus refusing laryngectomy with a hospital mortality of 5.5%. The overall 5-year actuarial survival, excluding the operative mortality, was 15.8%. After complete resection, better results were recorded with patients operated for carcinoma of the hypopharynx than with patients with carcinoma of the cervical esophagus: the 2-year and 5-year actuarial survival was 59% vs 26% and 43% vs 17%, respectively. No patient undergoing palliative resection was alive at the 3-year interval.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Surgical management of carcinoma of the hypopharynx and cervical esophagus.

Between 1975 and 1988 we observed 169 patients with carcinoma of the cervical esophagus, 85 with a carcinoma involving the hypopharynx and the cervical esophagus, and 27 with a carcinoma of the cervical esophageal region that developed after laryngectomy for laryngeal cancer. The mean age of the patients was 57.5 years (range: 41-73). One hundred and sixty-seven patients underwent surgical exploration (operability rate 59.5%), and in 152 cases the tumor was resected (resectability rate 91.1%). The resection was complete in 129 patients (84.5%) and palliative in 23 (14.5%). In 33 cases a laryngopharyngo-cervical segmental esophagectomy with free intestinal loop transplantation was performed, with an operative mortality of 6.1%. One hundred and three patients underwent laryngo-pharyngo-total esophagectomy, and the digestive tract was reconstructed by means of pharyngo-gastrostomy and pharyngo-colostomy in 85 and 16 cases, with an operative mortality of 12.9% and 18.3%, respectively. Total esophagectomy without laryngectomy was performed in 18 patients with a carcinoma of the distal cervical esophagus who refused laryngectomy, with an hospital mortality of 5.5%. The overall 5-year actuarial survival, excluding the operative mortality, was 15.8%. After complete resection, better results were recorded in patients operated on for carcinoma of the hypopharynx than in patients with carcinoma of the cervical esophagus: the 2-year and 5-year actuarial survival was 59% vs. 26% and 43% vs. 17%, respectively. No patient undergoing palliative resection was alive at the 3-year interval.(ABSTRACT TRUNCATED AT 250 WORDS)

Colon

[Surgical treatment of carcinoma of the hypopharynx and cervical esophagus].

Between 1975 and 1988 we observed 169 patients with carcinoma of the cervical esophagus, 85 a carcinoma involving the hypopharynx and the cervical esophagus, and 27 patients with a carcinoma of the cervical esophageal region arose after laryngectomy for laryngeal cancer. The mean age was 57.5 years (range 41-73). 167 patients underwent surgical exploration (operability rate 59.5%) and in 152 cases the tumor was resected (resectability rate 91.1%). The resection was complete in 129 patients (84.9%) and palliative in 23 (14.1%). In 33 cases of laryngo-pharyngo-cervical segmentary esophagectomy with free intestinal loop transplantation was performed with an operative mortality of 6.1%. 101 patients underwent laryngo-pharyngo-total esophagectomy and the digestive tract was reconstructed by means of pharyngo-gastrostomy and pharyngo-colostomy in 85 and 16 cases, with an operative mortality of 12.9% and 18.3%, respectively. Total esophagectomy without laryngectomy was performed in 18 patients with a carcinoma of the distal cervical esophagus refusing laryngectomy with an hospital mortality of 5.5%. The overall 5-year actuarial survival, excluding the operative mortality, was 15.8%. After complete resection, better results were recorded with patients operated for carcinoma of the hypopharynx than with patients with carcinoma of the cervical esophagus: the 2-year and 5-year actuarial survival was 59% vs 26% and 43% vs 17%, respectively. No patient undergoing palliative resection was alive at the 3-year interval.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Cancer of the hypopharynx and cervical esophagus. Role and limits of the surgical treatment].

From 1975 to 1988, we observed 169 patients with a carcinoma of the cervical esophagus, 85 with a carcinoma involving the hypopharynx and the cervical esophagus, and 27 with a carcinoma of the cervical esophagus occurring after laryngectomy for laryngeal carcinoma. The average age was 57.5 years (41-73). Exploration was surgical for 167 patients (operability ratio 59.5%), and the lesion was resected in 152 cases (resectability ratio 81.1%). Resection was complete in 129 patients (84.5%) and palliative in 23 (14.5%). A laryngopharyngoesophagectomy involving the cervical esophagus and requiring the transplantation of a free intestinal loop was performed in 33 cases, with an operative mortality rate of 6.1%. Pharyngolaryngectomy with total esophagectomy was performed in 101 patients, and the digestive tract was reconstructed by means of pharyngogastrostomy or pharyngocolostomy (respectively 85 and 16 cases) with an operative mortality rate of 12.9% and 18.3%, respectively. Complete esophagectomy without laryngectomy was performed for 18 patients with carcinoma of the distal cervical esophagus who refused laryngectomy, the hospital mortality rate being of 5.5%. The actuarial survival rate after 5 years (not including operative mortality) was 15.8%. Better results were achieved after complete resection for carcinoma of the hypopharynx than for carcinoma of the cerebral esophagus. The actuarial survival rates after 2 and 5 years were 59% vs. 26% and 43% vs. 17% respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis

[Esophagectomy without thoracotomy as a treatment of esophageal cancer. Indications, technical features and results].

Between 1980 and 1989, 229 patients with squamous cell carcinoma of the esophagus underwent esophagectomy without thoracotomy. The tumor was located in cervical and thoracic esophagus in 112 and 117 cases, respectively. Out the patient with a tumor of the thoracic esophagus, the mean age was 63 years (range 32-81). There were 90 males and 27 females. The locations inside the thoracic esophagus were as follows: upper thoracic 39, middle thoracic 40, lower thoracic 38 cases. A complete resection of the tumor was performed in 87 patients and in 30 cases the procedure was palliative. The digestive tract was reconstructed by means of esophago-gastrostomy in 101 patients, esophago-colostomy in 13, esophago-jejunostomy in 2, and pharyngo-colostomy in 1 patient, respectively. The post-operative morbidity was as follows: pulmonary complications 13.6%, anastomotic leak 17.1%, necrosis 5.1%, recurrent laryngeal nerve injuries 10.2%. The overall hospital mortality was 7.6%. Actuarial survival rates after curative and palliative resection were 82.4% and 47.1% at 7 year, 46.3% and 8.1% at 2 years, 39.0% and 0% at 3.5 and 6 years. In our experience, esophagectomy without thoracotomy is an excellent technique, with low morbidity but with oncologic limitations. Patients with carcinomas of the thoracic esophagus in whom thoracotomy is contraindicated can be resected with this technique with morbidity and mortality rates comparable to those of patients undergoing transthoracic esophagectomy.

Actuarial Analysis

How does liver dysfunction influence serum CA 19-9 in pancreatic cancer?

Serum CA 19-9 was determined in 83 control subjects, 99 patients with pancreatic cancer, 104 with chronic pancreatitis and 137 with extra-pancreatic diseases mainly of gastrointestinal origin in order to evaluate whether hepatic factors can influence circulating CA 19-9 in pancreatic cancer. Sensitivity, specificity and accuracy of this test in determining pancreatic malignancy were: 74%, 83% and 57%. We divided patients into two groups: group A (159 cases) and group B (181 cases) with and without anatomical liver damage (presence of primary or metastatic cancer, cirrhosis, hepatitis, steatofibrosis, cholangitis). Group A presented higher CA 19-9 values as compared to group B. Significant correlations were found in group B but not in group A between CA 19-9 and ALT, ALP and total bilirubin. Multiple regression analysis (CA 19-9 dependent and ALT, ALP and total bilirubin predictor variables) was significant only in group B. The standardized partial regression coefficients found to be significant were those of ALP and total bilirubin. We can conclude that CA 19-9 is an index of pancreatic cancer with satisfactory sensitivity and specificity. The presence of anatomical liver damage seems to increase the value of this index, probably releasing CA 19-9 into the bloodstream. Extra-hepatic cholestasis may also be an important factor in elevating CA 19-9 probably by reducing the hepatic catabolism of this glycoprotein.

Adult

Tumor markers in serum of patients with primary squamous cell carcinoma of the esophagus.

Serum levels of several tumor markers were studied in 96 patients with untreated primary squamous cell carcinoma of the esophagus. Three markers specific for digestive tract malignancies--CEA, CA19.9 and CA50--and two non organ specific indicators of malignancy--ferritin and TPA--were evaluated. Positivity rates of CA19.9 and CA50 were very low (4.4% and 8.6% respectively); the markers were therefore considered ineffective in the disease. CEA, TPA and ferritin showed a fair positivity rate (27.1%, 28.1%, 33.7% respectively); CEA and TPA were directly related to clinical stage, CEA levels being significantly higher in stage IV than in stage III cases (p = 0.016). TPA preoperatory levels were also directly related to a lower survival probability (p = 0.004). CEA showed significantly lower levels in tumors of lower than in those of middle (p = 0.03) and upper esophagus (p = 0.004). TPA showed a similar behaviour with lower levels in tumors of lower than of middle esophagus (p = 0.03). These findings could be due to a bulky metabolism of tumor markers drained via portail vein in the liver. From our data the following conclusions may be drawn: 1) CEA and TPA may be useful in the staging of esophageal cancer as an ancillary tool to assess the extent of the disease; 2) tumor location is an important variable when evaluating blood levels of tumor markers in patients with esophageal cancer.

Adult

[Use of a latissimus dorsi myocutaneous flap in locally advanced breast cancer].

Locally advanced breast cancer has a poor prognosis. Skin infiltration, ulceration and invasion of the chest wall, in the absence of distant metastases, worsen dramatically the quality of life. The Authors report 4 cases of one time wide resection and reconstruction using a pedicled myocutaneous flap of latissimus dorsi. This technique allowed good and rapid palliation of local symptoms.

Aged

[Early cancer of the esophagus: results in 61 operated cases].

From 1980 to 1987, 1338 patients with esophageal cancer were observed and 703 underwent esophagectomy. Pathologic exam of the operative specimen showed 61 early cancers of the esophagus: 10 mucosal and 51 submucosal. Hospital mortality in patients operated on (2 cases) for early esophageal cancer was 3.3% (2 cases). The 5-year survival rate in the cases of mucosal and submucosal tumors was 100% and 33%, respectively. The location of neoplastic recurrence was detected in 9 patients, all of whom had a submucosal tumor. The recurrence was local-regional in 4 cases, and remote in 5. The authors think that submucosal cancers of the esophagus may need a multimodality therapeutic approach to improve prognosis and prevent recurrence. Patients who are not surgical candidates and in whom the diagnosis of early cancer is likely on the basis of clinical staging may undergo endoscopic laser therapy.

Adult

Mastectomized woman's acquired knowledge about and attitude towards breast reconstruction. A prospective survey on 100 cases.

A prospective, study was carried out on 100 mastectomized women. Each patient was given a questionnaire concerning her awareness of the diagnosis, reaction to the operation, relationship with her own body, cosmetic solution chosen, feminine ideal, sources of information about breast reconstruction, acquired knowledge about it, attitude and motivation towards a possible plastic operation. This survey underlines that the relationship between the doctor and the neoplastic patient is hindered by the patient's lack of knowledge about her disease and about the possibility of rehabilitation by means of reconstructive surgery. 42% of the patients actually ignored the reason for their mutilation, and 53% of the women interviewed were shown not to be sufficiently informed about the possibility of plastic surgery, even though this kind of information has been recognised by many authors as fundamental for the patient's physical, psychological and esthetic welfare. 59% reported to have been informed by sources other than physicians although they are the most qualified. However 82% of all women showed a positive attitude towards the possibility of breast reconstruction: the mutilation experienced seemed to be such a strong motivation that factors such as sociocultural background and acquired knowledge about reconstruction itself were apparently unimportant.

Adult

Tumor markers in squamous cell carcinoma of esophagus: immunometric assay in cytosol and membrane fraction.

Carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), ferritin, and the monoclonal antibody-detected tumor-associated antigens CA19.9 and CA50 were measured by radioimmunoassay in tissue fractions of carcinoma and normal esophageal mucosa from 59 patients with untreated primary squamous cell carcinoma of the esophagus. Tumor markers were measured in cytosol (118 samples) and in a membrane-enriched fraction (32 samples). CEA, TPA and ferritin were detected in almost all the cytosol samples evaluated, CA19.9 and CA50 in 66% and 50% of cases respectively. Ferritin was significantly higher in carcinoma than in normal mucosa. The cytosol concentrations of CEA, TPA, CA19.9 and CA50 were not significantly different in carcinoma and normal tissue. Concentrations of CEA, CA19.9 and CA50 in the membrane fraction tended to be higher in normal tissue than in carcinoma, whereas the cytosol-to-membrane ratio was significantly higher in carcinoma. For CEA, CA19.9 and CA50, the phenotypic pattern of the malignant transformation seems to involve a different intracellular distribution rather than a quantitative change. No correlations were found between tissue and serum concentrations of the tumor markers, the former being related to the phenotypic characteristics of the tumor, the latter to the tumor burden.

Adult