Massive foreign body reaction and osteolysis following primary anterior cruciate ligament reconstruction with the ligament augmentation and reconstruction system (LARS): a case report with histopathological and physicochemical analysis.

BACKGROUND: Autologous hamstrings and patellar tendon have historically been considered the gold standard grafts for anterior cruciate ligament reconstruction (ACLR). In the last decades, the utilization of synthetic grafts has re-emerged due to advantageous lack of donor site morbidity and more rapid return to sport. The Ligament Augmentation and Reconstruction System (LARS) has demonstrated to be a valid and safe option for ACLR in the short term. However, recent studies have pointed out the notable frequency of associated complications, including synovitis, mechanical failure, and even chondrolysis requiring joint replacement. CASE PRESENTATION: We report the case of a 23-year-old male who developed a serious foreign body reaction with wide osteolysis of both femoral and tibial tunnels following ACLR with LARS. During first-stage arthroscopy, we performed a debridement of the pseudocystic mass incorporating the anterior cruciate ligament (ACL) and extending towards the tunnels, which were filled with autologous anterior iliac crest bone graft chips. Histological analysis revealed the presence of chronic inflammation, fibrosis, and foreign body giant cells with synthetic fiber inclusions. Furthermore, physicochemical analysis showed signs of fiber depolymerization, increased crystallinity and formation of lipid peroxidation-derived aldehydes, which indicate mechanical aging and instability of the graft. After 8 months, revision surgery was performed and ACL revision surgery with autologous hamstrings was successfully carried out. CONCLUSIONS: The use of the LARS grafts for ACLR should be cautiously contemplated considering the high risk of complications and early failure.

Increased visceral adipose tissue in male patients with non-clear cell renal cell carcinoma.

BACKGROUND: It is well known that there is a link between obesity and oncogenesis in many sites, including the kidney. Adiposopathy is characterized by an excessive accumulation of adipose tissue, principally visceral, which can lead to adipocyte and adipose tissue-related disorder, promoting metabolic syndrome. Visceral adipocytes secrete growth factors, proinflammatory cytokines and adipokines, regarded as mediating factors associated with the oncogenesis of obesity-related tumors. In this study, we evaluate the relationship between visceral adipose tissue (VAT) and non-clear cell renal cell carcinoma (nccRCC) in male patients. METHODS: In this retrospective study, two groups were included: nccRCC group and control group. Total adipose tissue (TAT) area, VAT area and subcutaneous adipose tissue (SAT) area were measured in both groups. VAT/SAT ratio was subsequently calculated. RESULTS: Statistically significant differences between the two groups were found in TAT area (p = 0.05), VAT area (p < 0.01) and VAT/SAT ratio (p < 0.05), while no significant difference was found in SAT area. CONCLUSIONS: This study demonstrates an increased visceral adipose tissue in male patients with nccRCC.

Morphometric analysis of atypical glandular cells correctly classifies normal, reactive, and atypical cells in cervical smears.

The 2014 Bethesda System diagnostic criteria for atypical glandular cells (AGC) aid in the classification of atypical cells in cervical cytology. Anyway, AGC diagnosis remains challenging, due to low frequencies of this finding (approximately 0.5%-1% of Pap test results), abundance of AGC mimics, and significant interobserver variability. We developed an algorithm based on nuclear areas parameter that can help to differentiate AGC from Normal and Reactive glandular cells. Nuclear areas and perimeters were measured on 16 Pap smears with AGC and 18 with Reactive glandular cells of women aged between 30 and 77. Glandular cells from nonpathological Pap smears were used as controls. For each case, the means, medians, standard deviations, and the minimum and maximum values of both nuclear areas and perimeters of the cells of interest were calculated. The nuclear area analysis showed a 100% specificity in discriminating Normal from Altered cells (either Reactive or AGC), whereas the nuclear perimeter analysis showed a lower specificity (87.5%). Both nuclear area and perimeter variability analysis resulted in high specificity values in distinguishing Reactive cells from AGC. Therefore, a stepwise two-step algorithm using nuclear areas to discriminate Normal from Altered cells, and nuclear area variability to distinguish Reactive from AGC, allowed us to reliably classify the cells into these three categories. The morphometric analysis of nuclear area is a valuable and reliable aid in AGC diagnosis and standardization, easily integrable into common automatic algorithms.

Heterogeneous risk profiles among B3 breast lesions of uncertain malignant potential.

BACKGROUND: Most cases of breast lesions of uncertain malignant potential (B3) undergo surgical intervention. We aimed to analyze the outcome of B3 lesion subtypes in a large series of screen-detected cases. METHODS: We screened 2,986 core needle biopsies to classify B3 lesions. Positive predictive values (PPVs) for malignancy were calculated for a comprehensive risk characterization according to clinicopathologic and morphologic variables. RESULTS: B3 lesions comprised 35% atypical ductal hyperplasia (PPV = 20%), 16.7% flat epithelial atypia (PPV = 12%), 22.7% lobular neoplasia (PPV = 16.2%), 9% papillary lesion (PPV = 18.5%), 8.6% phyllodes tumor (PPV = 3.8%), and 8% radial scars (PPV = 4.1%) based on histopathologic diagnosis. Upgrade rates were 15.9% for calcifications, 13.7% for mass lesions, and 16.7% for architectural deformities, with 8.3% of malignant lesions classified as ductal carcinoma in situ and 6.7% as invasive cancers (PPV = 15%). CONCLUSION: B3 lesions entail a heterogeneous risk of malignancy, and careful radiologic-pathologic correlation is required for optimal treatment.

Integrated transcriptomic and epigenomic analysis of ovarian cancer reveals epigenetically silenced GULP1.

Many epigenetically inactivated genes involved in ovarian cancer (OC) development and progression remain to be identified. In this study we undertook an integrated approach that consisted of identification of genome-wide expression patterns of primary OC samples and normal ovarian surface epithelium along with a pharmacologic unmasking strategy using 3 OC and 3 immortalized normal ovarian epithelial cell lines. Our filtering scheme identified 43 OC specific methylated genes and among the 5 top candidates (GULP1, CLIP4, BAMBI, NT5E, TGFß2), we performed extended studies of GULP1. In a training set, we identified GULP1 methylation in 21/61 (34%) of cases with 100% specificity. In an independent cohort, the observed methylation was 40% (146/365) in OC, 12.5% (2/16) in borderline tumors, 11% (2/18) in cystadenoma and 0% (0/13) in normal ovarian epithelium samples. GULP1 methylation was associated with clinicopathological parameters such as stage III/IV (p = 0.001), poorly differentiated grade (p = 0.033), residual disease (p < 0.0003), worse overall (p = 0.02) and disease specific survival (p = 0.01). Depletion of GULP1 in OC cells led to increased pro-survival signaling, inducing survival and colony formation, whereas reconstitution of GULP1 negated these effects, suggesting that GULP1 is required for maintaining cellular growth control.

Endoluminal Nd:YAG laser application in ex vivo biliary porcine tissue.

Adequate biliary drainage with endoscopic or percutaneous placement of self-expandable metal stents represents the goal of palliation in patients with inoperable malignant obstruction of the biliary tree. As an adjunct to stenting, various tissue ablation treatments have been proposed with conflicting results. The aim of this study was to test the effect on biliary tissue of a new ablation technique based on Nd:YAG laser light delivery. The study was conducted on ex vivo specimens of 18 healthy farm pigs, using cystic ducts that are the simplest biliary structures to isolate and cannulate ex vivo. A 22G cannula was positioned into the cystic duct and a quartz optical fibre, with a prototypal cooling system, was inserted into the cannula. Nd:YAG laser output powers of 10, 12, and 15 W were tested, with a total delivered energy of 1000 J in continuous mode in each case. After laser treatment, histological analysis was performed. At macroscopical examination, no lesions of the external wall of the cystic ducts were detected. At histopathological examination, a coagulative necrosis involving the entire mucosa up to the muscolaris propria without significant changes of periductal tissues was observed in all specimens. This study shows the possibility of using Nd:YAG laser on ex vivo porcine biliary ducts with the effect of obtaining a coagulative necrosis involving the whole mucosa.

Human equilibrative nucleoside transporter 1 gene expression is associated with gemcitabine efficacy in advanced leiomyosarcoma and angiosarcoma.

BACKGROUND: The expression of human equilibrative nucleoside transporter 1 (hENT1), the major gemcitabine transporter into cells, has been thoroughly investigated as a predictive marker of response to gemcitabine in pancreatic cancer and biliary tract cancers. Since gemcitabine is widely used in the treatment of leiomyosarcoma and angiosarcoma, we investigated the correlation between hENT1 expression and gemcitabine efficacy in these sarcoma subtypes. METHODS: We retrospectively identified 71 patients affected by advanced angiosarcoma (26) or leiomyosarcoma (45) treated within five Italian referral centres for sarcoma; among them, 49 patients (15 angiosarcoma, 34 leiomyosarcoma) were treated with gemcitabine. All tumour samples were analysed for hENT1 expression by real-time PCR. Median 2-ΔCt value was used as the cutoff to dichotomise patients into 'high' expression and 'low' expression groups. Kaplan-Meier analysis was performed to estimate progression-free survival (PFS) and overall survival (OS). RESULTS: We found a significant association between high hENT1 expression levels and favourable outcome in terms of PFS and OS compared to cases with low hENT1 expression in leiomyosarcoma treated with gemcitabine (PFS: 6.8 vs 3.2 months, P=0.004; OS: 14.9 vs 8.5 months, P=0.007). In addition, hENT1 overexpression correlated with a significant improvement in PFS (9.3 vs 4.5 months; P=0.02) and OS (20.6 vs 10.8 months; P=0.001) in angiosarcoma patients treated with gemcitabine. CONCLUSIONS: Our study suggests that higher hENT1 expression are associated to gemcitabine efficacy both in patients with advanced leiomyosarcoma and angiosarcoma.

HER2 Status in Gastric Cancer: Comparison between Primary and Distant Metastatic Disease.

HER2 (human epidermal growth factor receptor-2) assessment in histological samples of gastric cancer is essential to determine which patients might benefit from trastuzumab therapy. HER2 is often evaluated in primary tumor even if trastuzumab therapy is used to treat metastatic disease. However, the exact relationship in terms of HER2 status between primary and metastatic tumors has not been fully clarified. We aimed to evaluate the HER2 status concordance between primary gastric cancer and corresponding distant metastasis. HER2 status was evaluated by IHC (immunohistochemistry) and/or FISH ( fluorescence in situ hybridization) in 41 patients in primary gastric cancer and in paired metastasis. HER2 was assessed according scoring criteria applied in clinical approach. HER2 positivity was found in 14,6 % primary tumors and in 24,4%corresponding metastasis. HER2 concordance rate between primary and metastasis was 80,5 % (K-value = 0,388). Eight/41 (19,5 %)cases resulted discordant: 6 patients with metastatic HER2 positive lesions were found HER2 negative in primary cancers while 2 patient HER2 positive in primary lesion showed a negative conversion in metastasis. Our results showed a good concordance in terms of HER2 status between primary and metastatic lesions, as well as in biopsy and surgical removed specimens. However, the higher rate of HER2 positive status found in metastatic lesions underlined the importance of HER2 assessment in all samples obtained from different sites of gastric cancer disease.

Deregulation of dicer and mir-155 expression in liposarcoma.

Liposarcoma (LPS) is the most common soft tissue sarcoma. It has been demonstrated that mir-155 was the most overexpressed miRNA in well-differentiated LPS(WDLPS)/dedifferentiated LPS (DDLPS). The aim of this study is to evaluate the involvement of Dicer, Drosha and mir-155 in development of LPS and their possible role in stratification of different histological subtypes. Dicer, Drosha and mir-155 mRNA levels were analyzed in formalin-fixed paraffin-embedded specimens from patients diagnosed with 62 LPS and compared with samples of adipose tissues of healthy donors. The experimental data were obtained using qRT-PCR comparing Dicer, Drosha and mir-155 expression levels in tumor samples versus normal fat. The tumor samples from LPS patients showed a significantly lower Dicer expression versus normal adipose tissue, while Drosha levels did not differ. Concerning mir155 expression levels, our results demonstrated a significant mir-155 up-regulation in all LPS subtypes versus normal adipose tissue except for WDLS. These findings demonstrate for the first time that Dicer is deregulated in LPS and show that mir-155 is differentially expressed in LPS subgroups and it could be a promising tool to improve LPS disease stratification and differential diagnosis.