the problem in early diagnosis of sporadic cancer is understanding the individual's risk to develop disease. In response to this need, global scientific research is focusing on developing predictive ...models based on non-invasive screening tests. A tentative solution to the problem may be a cancer screening blood-based test able to discover those cell requirements triggering subclinical and clinical onset latency, at the stage when the cell disorder, i.e. atypical epithelial hyperplasia, is still in a subclinical stage of proliferative dysregulation.
a well-established procedure to identify proliferating circulating tumor cells was deployed to measure the cell proliferation of circulating non-haematological cells which may suggest tumor pathology. Moreover, the data collected were processed by a supervised machine learning model to make the prediction.
the developed test combining circulating non-haematological cell proliferation data and artificial intelligence shows 98.8% of accuracy, 100% sensitivity, and 95% specificity.
this proof of concept study demonstrates that integration of innovative non invasive methods and predictive-models can be decisive in assessing the health status of an individual, and achieve cutting-edge results in cancer prevention and management.
Graft-versus
-
host disease (GvHD) causes severe mucositis, impairs feeding and favors infection. The objective of this study was to identify the impact of GvHD in the oral cavity. We reviewed all ...consecutive patients who developed oral GvHD after HSCT. The study period was over 14 years. 53 patients were identified.
M
/
F
= 1.4; median age was 48.6 years; the median follow-up was for up to 3 years and 6 months. Conditioning regimens included several drugs (e.g., busulfan, cyclophosphamide and fludarabine). In 11 cases, radiotherapy (RT) was also used. Patients treated with RT were more likely to have tooth decay requiring fillings (
p
= 0.029), to need canal root interventions (
p
= 0.005) and to have tartar requiring oral hygiene interventions (
p
= 0.011). Patients with a lymphoma diagnosis were more likely to develop perioral scleroderma and chronic oral GvHD (cGvHD) (
p
= 0.045). Oral acute GvHD (aGvHD) was seen in 26 patients (49.1%). 21 (39.6%) patients developed cGvHD. GvHD of the tongue was seen in 21 (40%) patients. Oral mucositis was seen in only 5 patients (9.4%). Conditioning regimens with RT are more likely to induce oral aGvHD. The tongue is often affected by GvHD.
Graft versus host disease (GvHD) is a clinically important complication after allogeneic hematopoietic stem cell transplantation (HSCT). Its diagnosis relies on clinical and histopathological ...findings. In order to evaluate and improve inter-institutional diagnostic agreement on histological diagnosis and grading of acute gastrointestinal GvHD, we conducted a round robin test, which included 33 biopsies from 23 patients after HSCT. Five pathologists from different institutions independently evaluated the original sections from the biopsies submitted for diagnosis. Based on their results, consensus qualitative criteria for the assessment of typical histological features of GvHD (e.g., apoptosis, crypt destruction, mucosa denudation) were proposed, including detailed descriptions as well as histological images. In a second round robin test with involvement of the same pathologists, the reproducibility of both diagnosis and grading had improved. Remaining differences were mostly related to differential diagnostic considerations, including viral infection or toxic side effects of medication, which should be resolved by integrating histopathological findings with proper clinical information.
Abstract Objective The present study assessed the clinical outcome of patients conservatively treated for cervical adenocarcinoma in situ (AIS) and their predictive factors using univariate and ...multivariate population averaged (PA) generalized estimating equation (GEE) model in a longitudinal setting. Methods A series of 166 consecutive women (mean age 39.8 yrs; range 23–63 yrs) underwent conservative treatment of AIS as the primary treatment and were followed-up (mean 40.9 mo) using colposcopy, PAP-smear, biopsy and HPV-testing with Hybrid Capture 2. Results Hysterectomy was performed as part of the primary management in 47 patients, who were excluded from the follow-up (FU) analysis. Out of 119 women closely followed-up, additional therapeutic procedures were performed in 69. At study conclusion, 7 patients (5.9%) showed persistent disease, while 8 (6.7%) had progressed to invasive adenocarcinoma (AC). Positive HR-HPV test was the only independent predictor of disease recurrence (adjusted OR = 2.72; 95%CI 1.08–6.87), and together with free cone margins (OR = 0.20; 95%CI 0.04–0.92), HR-HPV positivity was also the single most powerful predictor of disease progression to AC, with OR = 3.74; 95%CI 1.84–7.61 (p = 0.0001) in multivariate PA-GEE. Conclusions These results suggest that testing HR-HPV positive at any time point during FU is the most significant independent predictor of progressive disease, while showing free margins in cone has a significant protective effect against progression to AC. Furthermore, because 4.3% women with persistent, recurrent or progressive disease experienced a late (5th and 6th FU) diagnosis of HG-CGIN or microinvasive AC, a close surveillance should be scheduled for at least three years in conservatively treated AIS patients.
A 48-year-old woman with neurofibromatosis type 1 (NF1) experienced progressive forearm swelling coupled with impending compartment syndrome. Computed tomography angiography revealed a ruptured ...aneurysm of the proximal radial artery, multiple fusiform radial artery aneurysms, and a high independent ulnar artery origin. Compartment syndrome required prompt hematoma evacuation. Radial artery reconstruction, technically demanding due to vessel wall fragility, was deemed unnecessary because of satisfactory blood supply to the hand. Histologic findings indicated NF1-related vascular abnormalities also in the apparently normal radial artery as well as in a forearm vein, suggesting diffused vasculopathy. This case report is the first on ruptured radial artery aneurysm in NF1-related polianeurysmatic degeneration.
To evaluate the clinical accuracy of Hepika test to identify cancer/precancerous lesions of the uterine cervix.
A multicentre retrospective study was carried out in 2018 and included 330 liquid-based ...cytology samples from three Italian centres of women aged 25-64 who had been tested for the human papillomavirus (HPV) and whose histology or follow-up outcome was known. Hepika is an enzyme-linked immunosorbent assay (ELISA) targeting the protein complexes E6#p53 and E7#pRb. After excluding samples without sufficient residual material, the clinical accuracy of Hepika test was evaluated in 274 samples: adenocarcinoma (ADC) (4), squamous cell carcinoma (SCC) (7), adenocarcinoma in situ (AIS) (1), cervical intraepithelial neoplasia (CIN) grade 3 (60), CIN2 (51), CIN1 (34), and negative histology (117). Association, sensitivity, and specificity for carcinoma, CIN3+ and CIN2+ are reported.
Positive Hepika test was associated with a high probability of carcinoma (odds ratio (DOR) = 33.68, 95% confidence interval (CI) 7.0-163.1); sensitivity was 81.8%, specificity, 88.2%. A positive Hepika test showed a weaker association with CIN3+ lesions (DOR = 3.5; 95% CI 1.75-6.99) and lower sensitivity (27.8%).
The Hepika test was found to be an accurate biomarker for HPV-induced cervical carcinoma. Population-based prospective studies are needed to confirm the clinical usefulness of the Hepika test in the differential diagnosis of HPV-induced invasive lesions.
Circulating microparticles (MP) have been described in sickle cell anaemia (SCA); however, their interaction with endothelial markers remains unclear. We investigated the relationship between MP, ...protein C (PC), free protein S (PS), nitric oxide (NO), endothelin-1 (ET-1) and adrenomedullin (ADM) in a large cohort of paediatric patients.
A total of 111 children of African ethnicity with SCA: 51 in steady state; 15 in crises; 30 on hydroxyurea (HU) therapy; 15 on transfusion; 17 controls (HbAA) of similar age/ethnicity. MP were analysed by flow cytometry using: Annexin V (AV), CD61, CD42a, CD62P, CD235a, CD14, CD142 (tissue factor), CD201 (endothelial PC receptor), CD62E, CD36 (TSP-1), CD47 (TSP-1 receptor), CD31 (PECAM), CD144 (VE-cadherin). Protein C, free PS, NO, pro-ADM and C-terminal ET-1 were also measured.
Total MP AV was lower in crisis (1.26×10
6
ml
−1
; 0.56-2.44×10
6
) and steady state (1.35×10
6
ml
−1
; 0.71-3.0×10
6
) compared to transfusion (4.33×10
6
ml
−1
; 1.6-9.2×10
6
, p<0.01). Protein C levels were significantly lower in crisis (median 0.52 IU ml
−1
; interquartile range 0.43-0.62) compared with all other groups: HbAA (0.72 IU ml
−1
; 0.66-0.82, p<0.001); HU (0.67 IU ml
−1
; 0.58-0.77, p<0.001); steady state (0.63 IU ml
−1
; 0.54-0.70, p<0.05) and transfusion (0.60 IU ml
−1
; 0.54-0.70, p<0.05). In addition, levels were significantly reduced in steady state (0.63 IU ml
−1
; 0.54-0.70) compared with HbAA (0.72 IU ml
−1
; 0.66-0.80, p<0.01). PS levels were significantly higher in HbAA (0.85 IU ml
−1
; 0.72-0.97) compared with crisis (0.49 IU ml
−1
; 0.42-0.64, p<0.001), HU (0.65 IU ml
−1
; 0.56-0.74, p<0.01) and transfusion (0.59 IU ml
−1
; 0.47-0.71, p<0.01). There was also a significant difference in crisis patients compared with steady state (0.49 IU ml
−1
; 0.42-0.64 vs. 0.68 IU ml
−1
; 0.58-0.79, p<0.05). There was high correlation (R>0.9, p<0.05) between total numbers of AV-positive MP (MP AV) and platelet MP expressing non-activation platelet markers. There was a lower correlation between MP AV and MP CD62P (R=0.73, p<0.05) (platelet activation marker), and also a lower correlation between percentage of MP expressing CD201 (%MP CD201) and %MP CD14 (R=0.627, p<0.001). %MP CD201 was higher in crisis (11.6%) compared with HbAA (3.2%, p<0.05); %MP CD144 was higher in crisis (7.6%) compared with transfusion (2.1%, p<0.05); %CD14 (0.77%) was higher in crisis compared with transfusion (0.0%, p<0.05) and steady state (0.0%, p<0.01); MP CD14 was detectable in a higher number of samples (92%) in crisis compared with the rest (40%); %MP CD235a was higher in crisis (17.9%) compared with transfusion (8.9%), HU (8.7%) and steady state (9.9%, p<0.05); %CD62E did not differ significantly across the groups and CD142 was undetectable. Pro-ADM levels were raised in chest crisis: 0.38 nmol L
−1
(0.31-0.49) versus steady state: 0.27 nmol L
−1
(0.25-0.32; p<0.01) and control: 0.28 nmol L
−1
(0.27-0.31; p<0.01). CT-proET-1 levels were reduced in patients on HU therapy: 43.6 pmol L
−1
(12.6-49.6) versus control: 55.1 pmol L
−1
(45.2-63.9; p<0.05). NO levels were significantly lower in chest crisis (19.3 mmol L
−1
plasma; 10.7-19.9) compared with HU (22.2 mmol L
−1
plasma; 18.3-28.4; p<0.05), and HbSC (30.6 mmol L
−1
plasma; 20.8-39.5; p<0.05) and approach significance when compared with steady state (22.5mmol L
−1
plasma; 16.9-28.2; p=0.07).
Protein C and free PS are reduced in crisis with lower numbers of platelet MP and higher percentage of markers of endothelial damage and of red cell origin. During chest crisis, ADM and ET-1 were elevated suggesting a role for therapy inhibiting ET-1 in chest crisis.
Summary Children with sickle cell anemia may undergo acute splenic sequestration. Splenectomy is performed in an attempt to reduce further events. Histologic studies of spleens have revealed the ...presence of granuloma-like nodules, known as Gamna-Gandy bodies with amorphous inclusions; however, their significance is unknown. The medical case records and histologic samples of consecutive children with sickle cell anemia treated with splenectomy between 2001 and 2007 at Our Lady's Children's Hospital, Dublin, were reviewed. Seventeen patients were identified. Gamna-Gandy bodies were studied by scanning electron microscopy and x-ray fluorescence spectroscopy. Gamna-Gandy bodies were identified in 7 (41%) patients, and amorphous inclusions were always seen. Patient age correlated significantly with Gamna-Gandy bodies ( P = .002). Scanning electron microscopic analysis demonstrated the crystalline nature of Gamna-Gandy bodies and the chemical composition (C 47.1%; O2 29.7%; P 9.0%; K+ 0.4%; Ca2+ 6.4%; Fe2+ 7.4%), whereas x-ray diffraction studied the structure (CaPO4 ∙ FeOH). A crystal-formation gradient was observed, increasing from the red pulp to the white pulp. Our study shows that Gamna-Gandy bodies contain crystals and that their formation is age dependent. We also demonstrated the crystal structure and chemical composition and the relationship between Gamna-Gandy bodies and chest crises presplenectomy or postsplenectomy.
Allogeneic bone marrow transplantation (BMT) is a procedure mostly used for high-risk hematologic malignances. In women, follow-up protocols after BMT include gynecologic checkups with Papanicolaou ...(Pap) smears.
We evaluated 117 Pap smears in 54 women who underwent allogeneic BMT and correlated the smear morphology with the BMT-related medical treatment.
Abnormal Pap smears after BMT were found in 13 (24.1%) women. Four (7.4%) women had at least one smear with atypical squamous cells of unknown significance, six (11.1%) had a low-grade squamous intraepithelial lesion, and three (5.6%) had atypical squamous cells/high-grade lesion cannot be excluded (ASC-H). The three patients with ASC-H showed high-grade atypia mimicking cancer but had a negative follow-up. Nine women, including the three with ASC-H, had undergone a conditioning therapy for BMT that included busulfan. No association between other drugs and therapy-related atypia was found.
Pap smears after BMT show a high incidence of dysplastic lesions. Moreover, conditioning including busulfan is often associated with therapy-related cytologic atypia, which may lead to unnecessary colposcopies and biopsies. Knowledge of the patient's history and a careful evaluation of the smears are mandatory in these cases.
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