Fixed Point-to-Point microwave wireless systems with high spectral efficiency are needed to meet the pervasive and increasing demand for capacity in back-haul networks of mobile radio systems. In ...this context, spatially multiplexed LoS-MIMO (Line-of-Sight Multiple Input Multiple Output) systems have been studied for about twenty years, particularly in the millimeter wave frequency bands (above 15 GHz). However, their deployment in real networks has been really limited, to the authors’ knowledge. This has been due to several factors, i.e. the practical possibility of using extremely high-level modulation formats (nowadays up to 8192-QAM), the joint use of co-channel dual polarization, and the availability of wider channel bands in the new high frequency ranges (e.g. E-Band). In addition, a crucial reason has been the difficulty of installing multiple antennas spaced apart in order to maximize the MIMO spatial multiplexing so providing the maximum capacity gain. This
optimal
antenna separation, even for the classical MIMO
M
×
N
with
M
= 2 antennas at the receiver and
N
= 2 antennas at the transmitter, can be several meters, e.g. 5.71 m at 23 GHz on a 5 km link. In this article, we analyze the performance of LoS-MIMO systems where antenna separation is highly sub-optimal, for limiting the array size, and a satisfactory performance is made possible by the exploitation of specific bit loading and power allocation strategies and the setting of the working region of the RF transmitter power amplifiers to operate at a given Signal-to-Inter Modulation Distortion Ratio (SIMDR). The result is an overview of the advantages and drawbacks of compact LoS-MIMO from a wider perspective than in the existing literature, including fundamental aspects for the practical implementation of these systems. Performance is discussed in many cases of interest and compared with the state of the art SISO (Single Input Single Output) system.
Objective
The aim of the paper is to provide an overview of intraoperative sampling methods for frozen section (FS) analysis and of surgical techniques for a secondary neurovascular bundle (NVB) ...resection, as the method of surgical margin (SM) sampling and the management of a positive SM (PSM) at the nerve‐sparing (NS) area are under evaluated issues. FS analysis during radical prostatectomy (RP) can help to tailor the plane of dissection based on cancer extension and thus extend the indications for NS surgery.
Evidence Acquisition
We performed a PubMed/Medical Literature Analysis and Retrieval System Online (MEDLINE), Web of Science, Cochrane Library, and Elton B. Stephens Co. (EBSCO)host search to include articles published in the last decade, evaluating FS analysis in the NS area and surgical attempts to convert a PSM to a negative status.
Evidence Synthesis
Overall, 19 papers met our inclusion criteria. The ways to collect samples for FS analysis included: systematic (analysing the whole posterolateral aspect of the prostate specimen, i.e., neurovascular structure‐adjacent frozen‐section examination NeuroSAFE); magnetic resonance imaging (MRI)‐guided (biopsies from MRI‐suspicious areas, retrieved by the surgeon in a cognitive way); and random biopsies from the soft periprostatic tissues.
Techniques to address a PSM in the NS area included: full resection of the spared NVB, from its caudal to cranial aspect, often including the rectolateral part of the Denonvilliers’ fascia; partial resection of the NVB, in cases where sampling attempts to localise a PSM; incremental approach, meaning a partial or full resection that extends until no prostate tissue is found in the soft periprostatic environment.
Conclusions
There is no homogeneity in prostate sampling for FS analysis, although most recent evidence is moving toward a systematic sampling of the entire NS area. The management of a PSM is variable and can be affected by the sampling strategy (difficult localisation of the persisting tumour at the NVB). The difficult identification of the exact soft tissue location contiguous to a PSM could be considered as the critical point of FS analysis and of spared‐NVB management.
The prognosis of patients with colorectal liver metastases (LMs) is mostly established on clinical variables or on the anatomic extent of colorectal cancer (CRC). Histopathological factors of LMs ...which may actually reflect the biological aggressiveness of the tumor are not routinely considered to define the risk of worse clinical outcome in those patients. The number of poorly differentiated clusters (PDCs) of neoplastic cells in primary CRC is associated with metastatic risk and bad prognosis, but PDC presence in LMs has been barely analyzed thus far. We assessed PDC presence in the histological slides of surgically resected and synchronous LMs in 63 patients with CRC who had been not submitted to any neoadjuvant treatments. Then, we analyzed its association with patients’ cancer-specific survival (CSS) or progression-free survival. The presence of PDCs (P = .016) and PDC localization at tumor edge of LMs (P = .0004) were significantly associated with shorter CSS. PDC presence at the periphery of LMs and positive resection margin were independent prognostic variables for CSS. PDC localization at the tumor edge of LMs was a significant (P = .0079) and independent prognosticator of shorter progression-free survival. Our data suggest that PDC presence and peripheral localization in LMs may be relevant to predict outcome and useful for clinical decision making in patients with colorectal synchronous LMs.
•The prognosis of patients with colorectal LM is commonly established on clinical features.•Low attention is given to histopathological features of LM as prognostic factors.•The number of PDCs in primary CRC is correlated with prognosis and metastatic disease.•This study shows that PDC presence and peripheral localization in synchronous colorectal LMs are associated with bad prognosis.•Assessment of PDC counting in synchronous LMs may be useful to assess prognosis and for clinical decision making in patients with stage IV CRC.
Ex vivo fluorescence confocal microscopy (FCM) is an innovative imaging tool that can be used intraoperatively to obtain real‐time images of untreated excised tissue with almost histologic ...resolution. As inflammatory diseases often share overlapping clinical features, histopathology evaluation is required for dubious cases, delaying definitive diagnoses, and therefore therapy. This study identifies key‐features at ex vivo FCM for differential diagnoses of cutaneous inflammatory diseases, in particular, psoriasis, eczema, lichen planus and discoid lupus erythematosus. Retrospective ex vivo FCM and histological evaluations with relevant diagnoses were correlated with prospectively reported histopathologic diagnoses, to evaluate agreement and the level of expertise required for correct diagnoses. We demonstrated that ex vivo FCM enabled the distinction of the main inflammatory features in most cases, providing a substantial concordance to histopathologic diagnoses. Moreover, ex vivo FCM and histological evaluations reached a substantial agreement with histopathologic diagnoses both for all raters and for each operator. After a yet to be defined learning curve, these preliminary results suggest that dermatologists may be able to satisfactorily interpret ex vivo FCM images for correct real‐time diagnoses. Despite some limitations mainly related to the equipment of FCM with a single objective lens, our study suggests that ex vivo FCM seems a promising tool in assisting diagnoses of cutaneous inflammatory lesions, with a level of accuracy quite close to that offered by histopathology. This is the first study to investigate ex vivo FCM application in cutaneous inflammatory lesions, and to evaluate the diagnostic capability of this technology.
AIM To clarify which factors may influence pathological tumor response and affect clinical outcomes in patients with locally advanced rectal carcinoma treated with neo-adjuvant chemoradiotherapy and ...surgery.METHODS Tumor regression grade(TRG) according to the Dworak system and yT NM stage were assessed and correlated with pre-treatment clinico-pathological variables in 215 clinically locally advanced(c TNM stage Ⅱ and Ⅲ) rectal carcinomas. Prognostic value of all pathological and clinical factors on disease free survival(DFS) and cancer specific survival(CSS) was analyzed by Kaplan Meier and Cox-regression analyses.RESULTS cN + status, mucinous histotype or poor differentiation in the pre-treatment biopsy were significantly associated with lower pathological response(low Dworak grade and TNM remaining unchanged/upstaging). Cases showing acellular mucin pools in surgical specimens all had unremarkable clinical courses with no deaths or recurrences during follow-up. Dworak grade had prognostic significance for DFS and CSS. However, compared to the 5-tiered system, a simplified twotiered grading system, in which grades 0, 1 and 2 were grouped as absent/partial regression and grades 3 and 4 were grouped as total/subtotal regression, was more reproducible and prognostically informative. The twotiered Dworak system, yN stage, craniocaudal extension of the tumor and radial margin status were significant independent prognostic variables. CONCLUSION Our data suggest that caution should be applied in using a conservative approach in rectal carcinomas with c N+ status, extensive/lower involvement of the rectum and mucinous histotype or poor differentiation. Although Dworak TRG is prognostically significant, a simplified two-tiered system could be preferable. Finally, cases with acellular mucin pools should be carefully evaluated to definitely exclude residual mucinous carcinoma.
Ulcerative colitis UC patients are at an increased risk of developing colorectal cancer due to chronic inflammation. Endoscopic submucosal dissection ESD allows removal of non-invasive neoplastic ...lesions in the colon, but few data are available on its efficacy in UC patients.
Data from consecutive UC patients diagnosed with visible dysplastic lesions in the colon who underwent ESD were evaluated. The en bloc removal, R0 resection and complication rates were calculated. Local recurrence and metachronous lesions during follow-up were identified. A systematic review of the literature with pooled data analysis was performed.
A total of 53 UC patients age: 65 years; range 30-74; M/F: 31/22 underwent ESD. The en bloc resection rate was 100%, and the R0 resection rate was 96.2%. Bleeding occurred in seven 13.2% patients, and perforation in three 5.6% cases, all treated at endoscopy. No recurrence was observed, but two metachronous lesions were detected. Data from six other studies three Asian and three European were available. By pooling data, en bloc resection was successful in 88.4% (95% confidence interval CI = 83.5-92) of 216 lesions and in 91.8% 95% CI = 87.3-94.8 of 208 patients. R0 resection was achieved in 169 ESDs, equivalent to a 78.2% 95% CI = 72.3-83.2 rate for lesions and 81.3% 95% CI = 75.4-86 rate for patients. No difference between European and Asian series was noted.
This pooled data analysis indicated that ESD is a suitable tool for safely and properly removing non-invasive neoplastic lesions on colonic mucosa of selected UC patients.
CDX2 is a transcription factor that acts as a tumor suppressor in colorectal cancer (CRC). Its loss triggers metastatic process and tumor progression; however, its prognostic role in patients with ...CRC is still controversial. Poorly differentiated clusters (PDCs) are aggregates of neoplastic cells which likely have high metastatic potential in CRC. In this study, we analyzed and compared CDX2 expression in PDC (CDX2-PDC) and corresponding main tumor (CDX2 main tumor) in 42 CRCs showing at least 10 PDC (PDC G3). Five of 42 CRCs (12%) were classified as CDX2 main tumor negative (4/5 were also PDC-CDX2 negative); all had tumor recurrence and died of CRC. Twenty nine of 42 cases were CDX2-PDC negative. Among CRC CDX2 main tumor positive, 15 had recurrences and 13 died from CRC; 13 and 11 of them, respectively, were CDX2-PDC negative. By assigning one point to CDX2 main tumor or CDX2-PDC positivity, we assessed CDX2-staining score for each case. Twelve cases had CDX2-staining score 2 (CDX2 positive in main tumor and PDC); 26 had score 1 (CDX2 positive in main tumor or PDC), and 4 had CDX2 score 0 (CDX2 negative in main tumor and PDC). In our patients, CDX2-staining score had higher prognostic value compared to CDX2 main tumor or CDX2-PDC alone. In addition, it represented a significant and independent prognostic variable for disease-free survival (DFS) and cancer-specific survival (CSS). Our findings suggest that, although loss of CDX2 in the main tumor identifies high-risk patients with high specificity, CDX2-PDC should also be considered in CDX2 main tumor positive cases to predict prognosis.
Background
Immunotherapy with immune checkpoint inhibitors (ICIs) is highly effective in microsatellite instability–high (MSI‐H) metastatic colorectal cancer (mCRC); however, specific predictive ...biomarkers are lacking.
Patients and Methods
Data and samples from 85 patients with MSI‐H mCRC treated with ICIs were gathered. Tumor infiltrating lymphocytes (TILs) and tumor mutational burden (TMB) were analyzed in an exploratory cohort of “super” responders and “clearly” refractory patients; TILs were then evaluated in the whole cohort of patients. Primary objectives were the correlation between the number of TILs and TMB and their role as biomarkers of ICI efficacy. Main endpoints included response rate (RR), progression‐free survival (PFS), and overall survival (OS).
Results
In the exploratory cohort, an increasing number of TILs correlated to higher TMB (Pearson's test, p = .0429). In the whole cohort, median number of TILs was 3.6 in responders compared with 1.8 in nonresponders (Mann‐Whitney test, p = .0448). RR was 70.6% in patients with high number of TILs (TILs‐H) compared with 42.9% in patients with low number of TILs (odds ratio = 3.20, p = .0291). Survival outcomes differed significantly in favor of TILs‐H (PFS: hazard ratio HR = 0.42, p = .0278; OS: HR = 0.41, p = .0463).
Conclusion
A significant correlation between higher TMB and increased number of TILs was shown. A significantly higher activity and better PFS and OS with ICI in MSI‐H mCRC were reported in cases with high number of TILs, thus supporting further studies of TIL count as predictive biomarker of ICI efficacy.
Implications for Practice
Microsatellite instability is the result of mismatch repair protein deficiency, caused by germline mutations or somatic modifications in mismatch repair genes. In metastatic colorectal cancer (mCRC), immunotherapy (with immune checkpoint inhibitors ICIs) demonstrated remarkable clinical benefit in microsatellite instability–high (MSI‐H) patients. ICI primary resistance has been observed in approximately 25% of patients with MSI‐H mCRC, underlining the need for predictive biomarkers. In this study, tumor mutational burden (TMB) and tumor infiltrating lymphocyte (TIL) analyses were performed in an exploratory cohort of patients with MSI‐H mCRC treated with ICIs, demonstrating a significant correlation between higher TMB and increased number of TILs. Results also demonstrated a significant correlation between high number of TILs and clinical responses and survival benefit in a large data set of patients with MSI‐H mCRC treated with ICI. TMB and TILs could represent predictive biomarkers of ICI efficacy in MSI‐H mCRC and should be incorporated in future trials testing checkpoint inhibitors in colorectal cancer.
This article explores the role of tumor mutational burden and number of tumor infiltrating lymphocytes in determining response and outcome of patients with microsatellite high metastatic colorectal cancer treated with immune checkpoint inhibitors.
Melanoma is the leading cause of death due to cutaneous malignancy and its incidence is on the rise. Several signaling pathways, including receptor tyrosine kinases, have a role in the development ...and progression of melanocytic lesions and malignant melanoma. Among those, the hepatocyte growth factor (HGF)/c-met axis is emerging as a critical player because it can play a role in drug resistance. Indeed, 50% of melanoma patients present BRAF mutations, however, all responders develop resistance to the inhibitors typically within one year of treatment. Interestingly, BRAF inhibitors induce reactive oxygen species (ROS) in melanoma cells, therefore, the aim of this study was to investigate a possible interplay between HGF/c-met and ROS sources, such as NADPH oxidases (Nox).
The expression of c-met and Nox were quantified in 60 patients with primary cutaneous melanoma. In vitro experiments on melanoma primary cells and the cell line were performed to dissect the underpinned molecular mechanism.
The outcome of interest was the correlation between the high positivity for both Nox4 and c-met and metastasis occurring at least 1 year later than melanoma diagnosis in BRAF mutated patients, in contrast to nonmutated. In vitro experiments demonstrated that the axis HGF/c-met/Nox4/ROS triggers the epithelial-mesenchymal transition.
The observed correlation suggests an interplay between c-met and Nox4 in promoting the onset of metastasis. This study suggests that Nox4 inhibitors could be associated to the current therapy used to treat melanoma patients with BRAF mutations.
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