Epidermal Growth Factor Receptor (EGFR) gene copy number (GCN) correlates with clinical activity of irinotecan-cetuximab in K-RAS wild-type colorectal cancer: a fluorescence in situ (FISH) and chromogenic in situ hybridization (CISH) analysis

<p>Abstract</p> <p>Background</p> <p>K-RAS wild type colorectal tumors show an improved response rate to anti-EGFR monoclonal antibodies. Nevertheless 70% to 40% of these patients still does not seem to benefit from this therapeutic approach. FISH EGFR GCN has been previously demonstrated to correlate with clinical outcome of colorectal cancer treated with anti-EGFR monoclonal antibodies. CISH also seemed able to provide accurate EGFR GCN information with the advantage of a simpler and reproducible technique involving immunohistochemistry and light microscopy. Based on these findings we investigated the correlation between both FISH and CISH EGFR GCN and clinical outcome in K-RAS wild-type colorectal cancer treated with irinotecan-cetuximab.</p> <p>Methods</p> <p>Patients with advanced K-RAS wild-type, colorectal cancer receiving irinotecan-cetuximab after failure of irinotecan-based chemotherapy were eligible.</p> <p>A cut-off value for EGFR GCN of 2.6 and 2.12 for FISH and CISH respectively was derived from ROC curve analysis.</p> <p>Results</p> <p>Forty-four patients were available for analysis. We observed a partial remission in 9 (60%) and 2 (9%) cases with a FISH EGFR GCN ≥ 2.6 and < 2.6 respectively (p = 0.002) and in 10 (36%) and 1 (6%) cases with a CISH EGFR GCN ≥ 2.12 and < 2.12 respectively (p = 0.03). Median TTP was 7.7 and 6.4 months in patients showing increased FISH and CISH EGFR GCN whereas it was 2.9 and 3.1 months in those with low FISH and CISH EGFR GCN (p = 0.04 and 0.02 respectively).</p> <p>Conclusion</p> <p>FISH and CISH EGFR GCN may both represent effective tools for a further patients selection in K-RAS wild-type colorectal cancer treated with cetuximab.</p

Dark sputum: An atypical presentation of primary pulmonary malignant melanoma

Primary melanoma of the lung is an extremely rare clinical entity. We found only 32 cases reported in literature, and in two of these multiple brain metastases were present. We describe a case of primary lung melanoma with brain and skin metastases that presented with an initial clinical diagnosis of pneumonia. A 55-year-old white man presented with cough productive of dark sputum and fever. A chest x-ray showed a right lung infiltration. After failure to respond to usual treatment for pneumonia, bronchoscopy examination and CT scan revealed a right pulmonary mass. The CT-guided biopsy confirmed a diagnosis of malignant melanoma. The primary lung origin of the tumor was demonstrated by the characteristic junctional pattern of melanoma cells. Further evaluation revealed metastases in the brain and in skin. Primary lung melanoma is an uncommon neoplasm that may be confused with more conventional types of lung cancer. Careful interpretation of histopathological information in correlation with all other clinical, laboratory and imaging studies may be needed to establish a diagnosis. Evaluation for metastases should include looking at the eyes, brain, skin. Due to the small number of cases reported in literature, there is no experience on the management and the prognosis of the disease

Primary Osteosarcoma of the Breast: A Case Report

Introduction. Primary osteosarcoma of the breast is a rare soft-tissue form of osteosarcoma without involvement of the skeletal system. Due to the rarity of the disease, its clinical features and optimal treatment remain unclear. Case Presentation. This case report deals with a 62-year-old woman with pure osteosarcoma of the breast. Conclusions. The prognosis of primary osteosarcoma of the breast is poor. Recurrence is frequent, and it is often associated with haematogenous spread of the disease to the lung. Treatment follows the model of sarcomas affecting other locations and must be planned in a multidisciplinary fashion. Adjuvant chemotherapy should be considered for patients with tumors showing aggressive features

Integrated Diagnostic Model That Incorporates Epstein-Barr Virus DNA, Imaging, and Nasal Endoscopy to Stratify Primary Tumor and Lymph Nodes in a Patient with N1 Nasopharyngeal Carcinoma: Multidisciplinary Management

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy, with a high metastatic potential. Epstein-Barr virus (EBV) infection plays a fundamental role, even if it is not well understood. The diagnosis of the disease in its early stage is infrequent. Imaging studies, positron emission tomography scans in addition to clinical examination, endoscopic examination, and biopsy provide information on the extent of the disease. The application of neoadjuvant chemotherapy followed by concomitant chemoradiation can improve the control of NPC. In March 2016, a 54-year-old male with NPC cT1 cN2 cM0, stage III (8th edition of American Joint Committee on Cancer (AJCC) staging system) underwent to a two-step treatment: induction chemotherapy by TPF regimen (docetaxel, cisplatin, 5-fluorouracil), followed by concomitant chemoradiotherapy (weekly cisplatin). The quantity of free plasma EBV-DNA can be related to the disease stage, and the detection of EBV-DNA during follow-up can be predictive of distant metastases. Especially, either plasma or serum EBV-DNA titer is estimated to reflect tumor volume. Biologically, such EBV-DNA reflects reproduced or released DNA from dead or dying tumor cells. On the other hand, EBV-specific DNA released as exosome may reflect the biological feature of the alive NPC tumor cell. The follow-up is ongoing after 21 months from a complete response

Isolation and characterization of mesenchymal cells from human fetal membranes

Bone marrow (BM) multipotent mesenchymal stromal cells (MSCs) present with multipotent differentiation potential and immunomodulatory properties. As an alternative to bone marrow, we have examined fetal membranes, amnion and chorion, of term human placenta as a potential source of multipotent MSCs. Here we show that amnion mesenchymal cells (AMCs) and chorion mesenchymal cells (CMCs), isolated by mechanical separation and subsequent enzymatic digestion, demonstrate plastic adherence and fibroblast-like morphology and are able to form colonies that could be expanded for at least 15 passages. By FACS analysis, AMCs and CMCs were shown to be phenotypically similar to BM-MSCs and, when cultured in differentiation media, they demonstrated high morphogenetic plasticity by differentiating into osteocytes, chondrocytes and adipocytes. In an attempt to isolate cells with MSC characteristics from human fetal membranes, AMCs and CMCs expressing CD271 were enriched by immunomagnetic isolation and were demonstrated to possess higher clonogenic and osteogenic differentiation potential than CD271-depleted fractions. Based on these findings, amnion and chorion can be considered as a novel and convenient source of adult MSC

Retrospective analysis of factors influencing oncologic outcome in 590 patients with early-intermediate glottic cancer treated by transoral laser microsurgery

BACKGROUND: The purpose of this study was to identify the factors influencing oncologic outcomes for patients with early-intermediate glottic cancer treated by transoral laser microsurgery (TLM). METHODS: This was a retrospective mono-institutional study. A total of 590 patients with cTis-cT3 glottic cancer underwent TLM with curative intent. RESULTS: TLM alone was performed in 538 patients (91.2%) and TLM followed by adjuvant radiotherapy (RT) was done in 52 (8.8%). Five-year recurrence-free survival (RFS) and 10-year overall survival (OS) were 85.3% and 74.7%, respectively. The larynx-preservation ratio was 95.9%. In particular, from our data, we found that occult metastases were rare (1.2%); preventive tracheotomy was not necessary; the local recurrence rate of Tis was similar to that in the T2 and T3 group; and no major or lethal complications were observed. CONCLUSION: Age (>60 vs ≤60), type of cordectomy (≥IV vs ≤III), status of margins, fixed arytenoid, and pathologic T classification, were the variables associated with RFS, OS, and organ-preservation rat

Preinvasive colorectal lesion transcriptomes correlate with endoscopic morphology (polypoid vs. nonpolypoid)

Improved colonoscopy is revealing precancerous lesions that were frequently missed in the past, and ∼30% of those detected today have nonpolypoid morphologies ranging from slightly raised to depressed. To characterize these lesions molecularly, we assessed transcription of 23,768 genes in 42 precancerous lesions (25 slightly elevated nonpolypoid and 17 pedunculated polypoid), each with corresponding samples of normal mucosa. Nonpolypoid versus polypoid morphology explained most gene expression variance among samples; histology, size, and degree of dysplasia were also linked to specific patterns. Expression changes in polypoid lesions frequently affected cell-cycling pathways, whereas cell-survival dysregulation predominated in nonpolypoid lesions. The latter also displayed fewer and less dramatic expression changes than polypoid lesions. Paradigmatic of this trend was progressive loss through the normal > nonpolypoid > polypoid > cancer sequence of TMIGD1 mRNA and protein. This finding, along with TMIGD1 protein expression patterns in tissues and cell lines, suggests that TMIGD1 might be associated with intestinal-cell differentiation. We conclude that molecular dysregulation in slightly elevated, nonpolypoid, precancerous colorectal lesions may be somewhat less severe than that observed in classic adenomatous polyps

Double-outlet left ventricle: single-center experience and literature review

Double-outlet left ventricle (DOLV) is an abnormal ventriculo-arterial connection characterized by origin of both great arteries, or more than 50% of each arterial root, from the morphological left ventricle. The aim of our paper is to describe the anatomic, echocardiographic, and multi-modality imaging characteristics of DOLV and associated malformations, and to assess its surgical outcomes. Methods: From 2011 to 2022, we retrospectively reviewed case records, intra-operatory reports and follow-up data of patients diagnosed with DOLV at Bambino Gesu Children’s Hospital. A systematic search was developed in MEDLINE, EMBASE and Web of Science databases, to identify original reports between January 1, 1975 and May 30, 2022, assessing the morphology and surgical outcomes of DOLV. Retrospective cohort studies, cross-sectional and case series were included in the analysis. Single case reports and reviews were excluded. Results: At our center, four cases of DOLV were identified. Patient 1 was diagnosed with (S,D,D) DOLV and hypoplastic right ventricle. The aorta overrode a large, doubly-committed VSD with absence of infundibular septum. A tenuous mitro-aortic discontinuity and a well-developed subpulmonary conus were present. Associated abnormalities included crossed pulmonary arteries and two adjacent, side-by-side coronary ostia, located in the anterior facing sinus, which gave origin to the left anterior descending (LAD) and the right coronary artery (RCA). Left circumflex artery (LCx) had a retro-aortic course and originated from the RCA. After pulmonary artery banding, Damus-Kaye-Stansel and Glenn intervention were proposed as first-stage of univentricular palliation. Patient 2 and 3 were diagnosed with (S,D,D) DOLV, subaortic VSD and pulmonary stenosis. Patient 2 underwent Rastelli operation and no anatomic detail were available. Patient 3 showed absence of the infundibular septum and mitro-pulmonary continuity, whereas subaortic conus was well developed. Anomalous origin of the LCx, originating from the posterior facing sinus with retro-aortic course was present. Rastelli procedure was performed to reconstruct right ventricular outflow tract. LCA and RCA were respectively caudal to subvalvular and supravalvular segments of the RV-to-PA conduit. After a 6-years follow-up, severe stenosis of the RV-to-PA conduit was present, nevertheless percutaneous conduit dilatation was contraindicated, due to coronary abnormality, and an aortic homograft was implanted Patient 4 was diagnosed with (S,D,L) DOLV with subaortic VSD and mitro-pulmonary fibrous continuity. A large subaortic conus was present. Reparation à l’etage ventriculaire was performed to reconstruct RVOT. Follow-up MRI at 8 years showed severe pulmonary artery regurgitation with mild RV dilatation (indexed volume 99mL/m2) and normal RV ejection fraction (54 %) Systematic review:Through our systematic research strategy we scrutinized 96 records for inclusion criteria (Figure 4). After systematic evaluation, a total of 9 reports fulfilled eligibility criteria and were included in our study. Morphological findings and surgical outcomes are summarized in Table 1. Among 191 cases of DOLV included, the most common subtypes of VSD were subaortic (128/191), subpulmonary (23/191) or doubly committed (14/191) (Figure 5). d-transposition of the aorta was present in 117/191 (61%) cases, whereas l-transposition was reported in 63/191 (32%) (Figure 6