ResearchPad - lymph-nodes https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Preoperative risk stratification in endometrial cancer (ENDORISK) by a Bayesian network model: A development and validation study]]> https://www.researchpad.co/article/elastic_article_14690 Bayesian networks are graphical networks that are based on machine learning and can be used for prediction purposes without the need to have values for all predictor variables available for each patient.Approximately 10% of patients with endometrial cancer have lymph node metastasis.The risk of lymph node metastasis and poor outcome differs substantially between individuals.Preoperative identification of patients at risk for lymph node metastasis and poor outcome allows tailoring of individualized treatment.What did the researched do and find?A Bayesian network to predict the risk of lymph node metastasis and survival was constructed with data from a retrospective multicenter development cohort from 10 centers across Europe (n = 763).The predictive capability of the final network was tested in 2 external cohorts from the Netherlands (PIpelle Prospective ENDOmetrial carcinoma [PIPENDO], n = 384) and from Norway (Molecular Markers in Treatment in Endometrial Cancer [MoMaTEC], n = 446).What do these findings mean?The Bayesian network we propose allows refined risk stratification before surgery and is easily usable.Because of its graphical character, the interactions between the different variables included into the network are directly visualized.A prospective feasibility study will be needed prior to implementation in the clinic. ]]> <![CDATA[Efficacy of adjuvant chemotherapy with S-1 in stage II oral squamous cell carcinoma patients: A comparative study using the propensity score matching method]]> https://www.researchpad.co/article/N83ad1f15-cdbb-4f4c-8d9c-388a45a97cce

It has been reported that 20% of early-stage oral squamous cell carcinoma (OSCC) patients treated with surgery alone (SA) may exhibit postoperative relapse within 2–3 years and have poor prognoses. We aimed to determine the safety of S-1 adjuvant chemotherapy and the potential differences in the disease-free survival (DFS) between patients with T2N0 (stage II) OSCC treated with S-1 adjuvant therapy (S-1) and those treated with SA. This single-center retrospective cohort study was conducted at Kumamoto University, between April 2004 and March 2012, and included 95 patients with stage II OSCC. The overall cohort (OC), and propensity score-matched cohort (PSMC) were analyzed. In the OC, 71 and 24 patients received SA and S-1, respectively. The time to relapse (TTR), DFS, and overall survival were better in the S-1 group, but the difference was not significant. In the PSMC, 20 patients each received SA and S-1. The TTR was significantly lower in the S-1 group than in the SA group, while the DFS was significantly improved in the former. S-1 adjuvant chemotherapy may be more effective than SA in early-stage OSCC.

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<![CDATA[Characterization of an intratracheal aerosol challenge model of Brucella melitensis in guinea pigs]]> https://www.researchpad.co/article/5c8823ccd5eed0c48463903c

B. melitensis is considered the most virulent of the Brucella species, and a need exists for an improved laboratory animal model of infection that mimics natural transmission and disease. Guinea pigs are highly susceptible to infection with Brucella spp. and develop a disease syndrome that mimics natural disease after aerosol inoculation. Intratracheal inoculation is a targeted means of generating aerosols that offer advantages over aerosol chamber delivery. To establish this delivery method, female, Hartley guinea pigs were infected via intratracheal inoculation with PBS or 16M B. melitensis at low dose (101 to 103) or high dose (106 to 108) and monitored for 30 days for signs of disease. Guinea pigs in the high dose groups developed fever between 12–17 days post-inoculation. Bacteria were recovered from the spleen, liver, lymph nodes, lung, and uterus at 30-days post-inoculation and demonstrated dose dependent mean increases in colonization and pathologic changes consistent with human brucellosis. To study the kinetics of extrapulmonary dissemination, guinea pigs were inoculated with 107 CFU and euthanized at 2-hours post inoculation and at weekly intervals for 3 weeks. 5.8x105 to 4.2x106 CFU were recovered from the lung 2 hours post-inoculation indicating intratracheal inoculation is an efficient means of infecting guinea pigs. Starting at 1-week post inoculation bacteria were recovered from the aforementioned organs with time dependent mean increases in colonization. This data demonstrates that guinea pigs develop a disease syndrome that models the human manifestation of brucellosis, which makes the guinea pig a valuable model for pathogenesis studies.

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<![CDATA[Hepatocellular carcinoma with extrahepatic metastasis: Are there still candidates for transarterial chemoembolization as an initial treatment?]]> https://www.researchpad.co/article/5c99029ed5eed0c484b98241

Background and aim

Currently, sorafenib is indicated for hepatocellular carcinoma (HCC) with extrahepatic metastasis (EHM), and many other systemic agents are becoming available. However, a few HCC patients with EHM still undergo transarterial chemoembolization (TACE) for intrahepatic tumor control. We aimed to investigate whether TACE is appropriate for patients with EHM, and if so, which subgroup may benefit from TACE.

Methods

A total of 186 consecutive HCC patients (median: 55 years, male: 86.0%, hepatitis B virus: 81.7%, Child-Pugh Class A: 83.3%) with EHM (nodal metastasis: 60.8%, distant metastasis: 39.2%) between 2010 and 2014 were analyzed. Initial treatment included sorafenib in 69 patients, and TACE in 117 patients.

Results

During a median follow-up of 6.6 months (range: 0.2–94.6 months), mortality was observed in 90.3% (168/186). The median survival was better for patients who received TACE than those treated with sorafenib (8.2 months vs. 4.6 months, p < 0.001). However, baseline characteristics varied between patients initially treated with TACE and sorafenib, and the treatment modality was not an independent factor associated with overall survival (hazard ratio: 1.19, 95% confidence interval: 0.81–1.75, p = 0.36). In sub-group analysis, TACE was associated with better survival only among younger patients and those with segmental/lobar portal vein invasion.

Conclusion

In HCC patients with EHM, TACE was not an independent favorable prognostic factor compared to sorafenib. The concept of intrahepatic control in HCC patients with EHM may need to be reevaluated in the era of promising systemic therapies, although there can be specific subgroups who still benefit from TACE.

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<![CDATA[The responses of lungs and adjacent lymph nodes in responding to Yersinia pestis infection: A transcriptomic study using a non-human primate model]]> https://www.researchpad.co/article/5c78500ed5eed0c484007bfd

Initiation of treatment during the pre-symptomatic phase of Yersinia pestis (Y. pestis) infection is particularly critical. The rapid proliferation of Y. pestis typically couples with the manifestation of common flu-like early symptoms that often misguides the medical intervention. Our study used African green monkeys (AGM) that did not exhibit clear clinical symptoms for nearly two days after intranasal challenge with Y. pestis and succumbed within a day after showing the first signs of clinical symptoms. The lung, and mediastinal and submandibular lymph nodes (LN) accumulated significant Y. pestis colonization immediately after the intranasal challenge. Hence, organ-specific molecular investigations are deemed to be the key to elucidating mechanisms of the initial host response. Our previous study focused on the whole blood of AGM, and we found early perturbations in the ubiquitin-microtubule-mediated host defense. Altered expression of the genes present in ubiquitin and microtubule networks indicated an early suppression of these networks in the submandibular lymph nodes. In concert, the upstream toll-like receptor signaling and downstream NFκB signaling were inhibited at the multi-omics level. The inflammatory response was suppressed in the lungs, submandibular lymph nodes and mediastinal lymph nodes. We posited a causal chain of molecular mechanisms that indicated Y. pestis was probably able to impair host-mediated proteolysis activities and evade autophagosome capture by dysregulating both ubiquitin and microtubule networks in submandibular lymph nodes. Targeting these networks in a submandibular LN-specific and time-resolved fashion could be essential for development of the next generation therapeutics for pneumonic plague.

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<![CDATA[Liver metastasis and Heng risk are prognostic factors in patients with non-nephrectomized synchronous metastatic renal cell carcinoma treated with systemic therapy]]> https://www.researchpad.co/article/5c76fe33d5eed0c484e5b6ea

Objective

This study aimed to determine the prognostic factors of progression-free survival (PFS) and overall survival (OS) in non-nephrectomized patients with synchronous metastatic renal cell carcinoma (mRCC) receiving first-line vascular endothelial growth factor (VEGF)-targeted therapy or immunotherapy.

Methods

Of 70 patients, 57 (81.4%) were treated with targeted therapy, including 5 (7.1%) with previous immunotherapy and 13 (18.6%) with immunotherapy only. The medical records of patients were retrospectively reviewed and analyzed to determine factors of PFS and OS using the Cox proportional hazards model with a statistical significance p-value <0.05.

Results

The median treatment and follow-up periods were 3.9 and 30.9 months, respectively. Disease progression was reported in 90.0% of patients, with an objective response rate and clinical benefit rate of 26.1% and 76.8%, respectively. The lung (77.1%) was the most common site of metastasis. Multivariable analysis showed that poor Heng risk (hazard ratio [HR]: 2.37) and liver metastasis (HR: 2.34) were significant prognostic factors for PFS, and female sex (HR: 2.13), poor Heng risk (HR: 3.14), and liver metastasis (HR: 2.78) were significant prognostic factors for OS (p < 0.05). A subset analysis of risk factors among patients without previous history of immunotherapy also showed poor Heng risk (HR 2.92 and HR 4.24 for PFS) and liver metastasis (HR 2.87 and HR 4.81 for OS) as significant factors for both PFS and OS (p<0.05).

Conclusion

Poor Heng risk, sex, and liver metastasis were associated with survival outcomes after first-line systemic therapy in patients with non-nephrectomized synchronous mRCC.

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<![CDATA[Serological and molecular detection of Bartonella henselae in specimens from patients with suspected cat scratch disease in Italy: A comparative study]]> https://www.researchpad.co/article/5c673073d5eed0c484f37b74

Cat scratch disease (CSD) is an infectious disease caused by Bartonella henselae, usually characterized by self-limiting regional lymphadenopathy and fever. Given the low clinical diagnostic sensitivity and specificity of conventional anti-B. henselae indirect immunofluorescence assays (IFAs), real-time polymerase chain reaction (PCR)-based detection of B. henselae is now being proposed as a more sensitive tool to diagnose CSD. Thus, here we have assessed the efficacy of real-time PCR in detecting B. henselae in different specimens from patients with suspected CSD and compared it to that of IFA. From March 2011 to May 2016, at the Microbiology and Virology Unit, Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino, Turin, Italy, 115 clinical specimens (56 aspirated pus, 39 fresh lymph node biopsies, and 20 whole blood samples) and 99 sera from 115 patients with suspected CSD (62 females and 53 males between the ages of 3 months and 68 years) were analyzed by both real-time PCR, used in a qualitative way, and IFA (IgM and IgG) for the presence of B. henselae. For 16 patients, serological results were not available due to a clinical decision not to request the test. B. henselae DNA positivity was detected by real-time PCR in 37.39% of patients, while 62.61% of them were negative. Thus, patients were divided into two groups: real-time PCR+ (n = 43) and real-time PCR- (n = 72). Real-time PCR screening of whole blood, biopsies, and aspirated pus revealed B. henselae positivity in 40%, 38.46%, and 35.71% of patients, respectively. When we analyzed samples by IFA, we found the presence of B. henselae in 28 out of 99 (28.28%) patients, of which 11 (11.11%) belonged to the real-time PCR+ group and 17 (17.17%) to the real-time PCR- group. Among the 71 seronegative subjects, 16 (16.16%) were found positive for B. henselae by real-time PCR. Thus, by combining the results of both assays, we were able to increase the percentage of B. henselae positive specimens from 27.27% (real-time PCR) or 28.28% (IFA) to 44.44% (real-time PCR+IFA). Altogether, these findings indicate that the early detection of B. henselae in patients with suspicious CSD through combined real-time PCR and serological analyses can lead to a more accurate diagnosis of CSD, thereby allowing prompt and appropriate disease management.

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<![CDATA[Clinical outcomes and dosimetric study of hypofractionated Helical TomoTherapy in breast cancer patients]]> https://www.researchpad.co/article/5c5ca2a6d5eed0c48441e7f4

We present a single center’s experience of treatment outcomes and dosimetric parameters for breast cancer patients treated with hypofractionated Helical TomoTherapy (HT). This is a retrospective study of one hundred and thirty-six patients with invasive breast cancer treated between March 2012 and October 2016. Dosimetric parameters and 3-year loco-regional failure free survival (LRFFS) were analyzed. Dose to ipsilateral lung, heart and contralateral breast as well as acute and late toxicities were recorded. The median follow-up time is 45 months (range: 5–83). Two patients had loco-regional failure. The 3-year LRFFS was 99%. Acute grade 1 and 2 skin toxicities occurred in 95% and 1%, respectively. Coverage of the target volumes was achieved with the mean ± standard deviation (SD) of homogeneity and conformity index being 0.1 ± 0.04, and 0.8 ± 0.07, respectively. Dose to ipsilateral lung, contralateral breast, and heart was also within the limited constraints regardless of the complexity of target volumes. Only two percent of patients experienced late grade 2 skin toxicity. No late grade 2 subcutaneous tissue toxicity was found. Nine percent of patients developed late grade 1 lung toxicity. Hypofractionated radiotherapy using Helical TomoTherapy in breast irradiation provides excellent 3-year LRFFS and minimal acute and late toxicities. A careful, longer follow-up of healthy tissue effects to lung, heart, and contralateral breast is warranted.

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<![CDATA[The Apparent Diffusion Coefficient (ADC) is a useful biomarker in predicting metastatic colon cancer using the ADC-value of the primary tumor]]> https://www.researchpad.co/article/5c633946d5eed0c484ae63d7

Purpose

To investigate the role of the apparent diffusion coefficient (ADC) as a potential imaging biomarker to predict metastasis (lymph node metastasis and distant metastasis) in colon cancer based on the ADC-value of the primary tumor.

Methods

Thirty patients (21M, 9F) were included retrospectively. All patients received a 1.5T MRI of the colon including T2 and DWI sequences. ADC maps were calculated for each patient. An expert reader manually delineated all colon tumors to measure mean ADC and histogram metrics (mean, min, max, median, standard deviation (SD), skewness, kurtosis, 5th-95th percentiles) were calculated. Advanced colon cancer was defined as lymph node mestastasis (N+) or distant metastasis (M+). The student Mann Whitney U-test was used to assess the differences between the ADC means of early and advanced colon cancer. To compare the accuracy of lymph node metastasis (N+) prediction based on morpholigical criteria versus ADC-value of the primary tumor, two blinded readers, determined the lymph node metastasis (N0 vs N+) based on morphological criteria. The sensitivity and specificity in predicting lymph node metastasis was calculated for both readers and for the ADC-value of the primary tumor, with histopathology results as the gold standard.

Results

There was a significant difference between the mean ADC-value of advanced versus early tumors (p = 0.002). The optimal cut off value was 1179 * 10−3 mm2/s with an area under the curve (AUC) of 0.83 and a sensitivity and specificity of 81% and 86% respectively to predict advanced tumors. Histogram analyses did not add any significant additional value.

The sensitivity and specificity for the prediction of lymph node metastasis based on morphological criteria were 40% and 63% for reader 1 and 30% and 88% for reader 2 respectively. The primary tumor ADC-value using 1.179 * 10−3 mm2/s as threshold had a 100% sensitivity and specificity in predicting lymph node metastasis.

Conclusion

The ADC-value of the primary tumor has the potential to predict advanced colon cancer, defined as lymph node metastasis or distant metastasis, with lower ADC values significantly associated with advanced tumors. Furthermore the ADC-value of the primary tumor increases the prediction accuracy of lymph node metastasis compared with morphological criteria.

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<![CDATA[Intensity-modulated radiotherapy for prostate cancer with seminal vesicle involvement (T3b): A multicentric retrospective analysis]]> https://www.researchpad.co/article/5c79b004d5eed0c4841e3c37

Objectives

No study has reported clinical results of external-beam radiotherapy specifically for T3b prostate cancer. The possibility of escalating the dose to the involved seminal vesicles (ISV) while respecting the dose constraints in the organs at risk is thus so far not clearly demonstrated. The objective of the study was to analyze the dose distribution and the clinical outcome in a large series of patients who received IMRT for T3b prostate cancer.

Materials and methods

This retrospective analysis included all patients who received IMRT and androgen deprivation therapy for T3b prostate cancer, between 2008 and 2017, in six French institutions, with available MRI images and dosimetric data.

Results

A total of 276 T3b patients were included. The median follow-up was 26 months. The median (range) prescribed doses (Gy) to the prostate and to the ISV were 77 (70–80) and 76 (46–80), respectively. The dose constraint recommendations were exceeded in less than 12% of patients for the rectum and the bladder. The 5-year risks of biochemical and clinical recurrences and cancer-specific death were 24.8%, 21.7%, and 10.3%, respectively. The 5-year risks of local, pelvic lymph node, and metastatic recurrences were 6.4%, 11.3%, and 15%, respectively. The number of involved lymph nodes (≤ 2 or ≥ 3) on MRI was the only significant prognostic factor in clinical recurrence (HR 9.86) and death (HR 2.78). Grade ≥ 2 acute and 5-year late toxicity rates were 13.2% and 12% for digestive toxicity, and 34% and 31.5% for urinary toxicity, respectively. The dose to the pelvic lymph node and the age were predictive of late digestive toxicity.

Conclusion

IMRT for T3b prostate cancer allows delivery of a curative dose in the ISV, with a moderate digestive toxicity but a higher urinary toxicity. Lymph node involvement increases the risk of recurrence and death.

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<![CDATA[Prediction of local recurrence risk after neoadjuvant chemotherapy in patients with primary breast cancer: Clinical utility of the MD Anderson Prognostic Index]]> https://www.researchpad.co/article/5c5ca2e2d5eed0c48441ec55

Background

Locoregional recurrence after neoadjuvant chemotherapy for primary breast cancer is associated with poor prognosis. It is essential to identify patients at high risk of locoregional recurrence who may benefit from extended local therapy. Here, we examined the prediction accuracy and clinical applicability of the MD Anderson Prognostic Index (MDAPI).

Methods

Prospective clinical data from 456 patients treated between 2003 and 2011 was analyzed. The Kaplan-Meier method was used to examine the probabilities of locoregional recurrence, local recurrence and distant metastases according to individual prognosis score, stratified by type of surgery (breast conserving therapy or mastectomy). The possible confounding of the relationship between recurrence risk and MDAPI by established risk factors was accounted for in multiple survival regression models. To define the clinical utility of the MDAPI we analyzed its performance to predict locoregional recurrence censoring patients with prior or simultaneous distant metastases.

Results

Mastectomized patients (42% of the patients) presented with more advanced tumor stage, lower tumor grade, hormone-receptor positive disease and consequently lower pathological complete response rates. Only a few patients presented with high-risk scores (2,7% MDAPI≥3). All patients with high-risk MDAPI score (MDAPI ≥3) who developed locoregional recurrence were simultaneously affected by distant metastases.

Conclusion

Our data do not support a clinical utility of the MDAPI to guide local therapy.

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<![CDATA[A secreted schistosome cathepsin B1 cysteine protease and acute schistosome infection induce a transient T helper 17 response]]> https://www.researchpad.co/article/5c4a305fd5eed0c4844bfeae

The natural history of schistosome infection in the mammalian host is determined by CD4+ T helper responses mounted against different parasite life cycle stages. A T helper 2 (TH2) response to schistosome eggs is required for host survival and establishment of chronic infection. However, a TH2 cell-derived cytokine also contributes to an immune milieu that is conducive to schistosome growth and development. Thus, the same responses that allow for host survival have been co-opted by schistosomes to facilitate parasite development and transmission, underscoring the significance of CD4+ T cell responses to both worms and eggs in the natural history of schistosome infection. Here we show that a cathepsin B1 cysteine protease secreted by schistosome worms not only induces TH2 responses, but also TH1 and TH17 responses, by a mechanism that is dependent on the proteolytic activity of the enzyme. Further investigation revealed that, in addition to the expected TH1 and TH2 responses, acute schistosome infection also induces a transient TH17 response that is rapidly down-regulated at the onset of oviposition. TH17 responses are implicated in the development of severe egg-induced pathology. The regulation of worm-induced TH17 responses during acute infection could therefore influence the expression of high and low pathology states as infection progresses.

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<![CDATA[Anatomical location-based nodal staging system is superior to the 7th edition of the American Joint Committee on Cancer staging system among patients with surgically resected, histologically low-grade gastric cancer: A single institutional experience]]> https://www.researchpad.co/article/5c63395fd5eed0c484ae6576

Background

A hybrid topographic and numeric lymph node (LN) staging system for gastric cancer, which was recently proposed by Japanese experts as a simple method with a prognostic predictive power comparable to the N staging of the American Joint Committee on Cancer (AJCC) Tumor-node-metastasis classification, has not yet been validated in other Asian countries. This study aimed to examine the prognostic predictability of the hybrid staging system with the current AJCC staging system in gastric cancer.

Methods

Overall, 400 patients with gastric cancer who underwent surgery at Changhua Christian Hospital from January 2007 to December 2017 were included in the study. Univariate and multivariate analyses were performed to identify prognostic factors for gastric cancer-related death. Homogeneity and discrimination abilities of the two staging systems were compared using likelihood ratio chi-square test, linear trend chi-square test, Harrell’s c-index, and bootstrap analysis.

Results

One-third of the LN-positive patients were reclassified into the new N and Stage system. The concordance rates of the two staging systems and the N staging between the two staging systems were 0.810 and 0.729, respectively. Harrell’s c-indices for the stage and N staging were higher in the 7th AJCC staging system than the hybrid staging system (c-index for stage, 0.771 vs 0.764; c-index for nodal stage, 0.713 vs 0.705). Stratification of the patients according to the histological grade revealed that Harrell’s c-indices for the stage and N stage of the hybrid staging system were comparable with those of the 7th AJCC staging system (c-index for AJCC stage vs hybrid stage, 0.800 vs 0.791; c-index for AJCC N stage vs hybrid N stage, 0.746 vs 0.734) among patients with histologically lower grade gastric cancer. The performance of the new nodal staging system was better than that of the 7th AJCC staging system by likelihood ratio and linear trend tests and bootstrap analysis in the low-grade group.

Conclusions

The hybrid anatomical location-based classification may have better prognostic predictive ability than the 7th AJCC staging system for LN metastasis of low-grade gastric cancer. Further studies involving different ethnic populations are necessary for the validation of the new staging system.

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<![CDATA[Prognostic value of uPAR expression and angiogenesis in primary and metastatic melanoma]]> https://www.researchpad.co/article/5c466554d5eed0c484518a14

Angiogenesis is important for the progression of cutaneous melanoma. Here, we analyzed the prognostic impact of the angiogenic factor urokinase plasminogen activator resecptor (uPAR), vascular proliferation index (VPI) and tumor necrosis as a measure of hypoxia in a patient series of nodular melanomas (n = 255) and matched loco-regional metastases (n = 78). Expression of uPAR was determined by immunohistochemistry and VPI was assessed by dual immunohistochemistry using Factor-VIII/Ki67 staining. Necrosis was recorded based on HE-slides. As novel findings, high uPAR expression and high VPI were associated with each other, and with increased tumor thickness, presence of tumor necrosis, tumor ulceration, increased mitotic count and reduced cancer specific survival in primary melanoma. In matched cases, VPI was decreased in metastases, whereas the frequency of necrosis was increased. Our findings demonstrate for the first time the impact on melanoma specific survival of uPAR expression and VPI in primary tumors, and of increased necrosis as an indicator of tumor hypoxia in loco-regional metastases. These findings support the importance of tumor angiogenesis in melanoma aggressiveness, and suggest uPAR as an indicator of vascular proliferation and a potential biomarker in melanoma.

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<![CDATA[Comparison of the binding of the gastrin-releasing peptide receptor (GRP-R) antagonist 68Ga-RM2 and 18F-FDG in breast cancer samples]]> https://www.researchpad.co/article/5c478c7dd5eed0c484bd29e8

The Gastrin-Releasing Peptide Receptor (GRPR) is over-expressed in estrogen receptor (ER) positive breast tumors and related metastatic lymph nodes offering the opportunity of imaging and therapy of luminal tumors. 68Ga-RM2 binding and 18F-FDG binding in tumoral zones were measured and compared using tissue micro-imaging with a beta imager on 14 breast cancer samples (10 primaries and 4 associated metastatic lymph nodes). Results were then assessed against ER expression, progesterone receptor (PR) expression, HER2 over-expression or not and Ki-67 expression. GRPR immunohistochemistry (IHC) was also performed on all samples. We also retrospectively compared 68Ga-RM2 and 18F-FDG bindings to 18F-FDG SUVmax on the pre-therapeutic PET/CT examination, if available. 68Ga-RM2 binding was significantly higher in tumors expressing GRPR on IHC than in GRPR-negative tumors (P = 0.022). In ER+ tumors, binding of 68Ga-RM2 was significantly higher than 18F-FDG (P = 0.015). In tumors with low Ki-67, 68Ga-RM2 binding was also significantly increased compared to 18F-FDG (P = 0.029). Overall, the binding of 68Ga-RM2 and 18F-FDG displayed an opposite pattern in tumor samples and 68Ga-RM2 binding was significantly higher in tumors that had low 18F-FDG binding (P = 0.021). This inverse correlation was also documented in the few patients in whom a 18F-FDG PET/CT examination before surgery was available. Findings from this in vitro study suggest that GRPR targeting can be an alternative to 18F-FDG imaging in ER+ breast tumors. Moreover, because GRPR antagonists can also be labeled with lutetium-177 this opens new avenues for targeted radionuclide therapy in the subset of patients with progressive metastatic disease following conventional treatments.

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<![CDATA[Plasma growth differentiation factor-15 is an independent marker for aggressive disease in endometrial cancer]]> https://www.researchpad.co/article/5c478c52d5eed0c484bd1926

Objective

Better biomarkers are needed in order to identify patients with endometrial carcinoma at risk of recurrence and who may profit from a more aggressive treatment regimen. Our objective was to explore the applicability of plasma growth differentiation factor 15 (GDF-15) as a marker for recurrent disease, as well as a marker for poor prognosis and lymph node metastases.

Methods

EDTA-blood samples were obtained from 235 patients with endometrial cancer before primary surgery. For 36 of these patients, matching blood samples were collected at time of recurrence. Blood samples were also collected from 78 patients with endometrial hyperplasia. Plasma GDF-15 was measured by an enzyme-linked immunosorbent assay (ELISA). Preoperative pelvic MRI scans for 141 patients were investigated in parallel for imaging variables.

Results

Preoperative plasma level of GDF-15 was significantly higher for patients who experienced recurrence (1780 ng/L; 95% CI; 518–9475 ng/L) than for patients who did not develop recurrent disease (1236 ng/L; 95% CI; 307–7030 ng/L) (p<0.001). Plasma levels of GDF-15 at recurrence (2818 ng/L, 95% CI 2088–3548 ng/L) were significantly higher than plasma levels of GDF-15 measured at time of primary diagnosis (1857 ng/L, 95% CI; 1317–2398 ng/L) (p = 0.001). High plasma level GDF-15 independently predicts recurrent disease (OR = 3.14; 95% CI 2.10–4.76) and lymph node metastases (OR = 2.64; 95% CI 1.52–4.61). Patients with high plasma level of GDF-15 had significantly larger tumor volume (p = 0.008).

Conclusion

Elevated plasma level of GDF-15 is associated with aggressive disease and lymph node metastasis in endometrial carcinoma. GDF-15 may be helpful in indicating recurrent disease.

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<![CDATA[Clinical efficacy and cost-effectiveness of endobronchial ultrasound-guided transbronchial needle aspiration for preoperative staging of non-small–cell lung cancer: Results of a French prospective multicenter trial (EVIEPEB)]]> https://www.researchpad.co/article/5c3d0157d5eed0c48403a6dd

This two-step study evaluated the cost-effectiveness of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for presurgery staging of non-small cell lung cancer (NSCLC) in France (EVIEPEB; ClinicalTrial.gov identifier NCT00960271).

Step 1 consisted of a high-benchmark EBUS-TBNA–training program in participating hospital centers. Step 2 was a prospective, national, multicenter study on patients with confirmed or suspected NSCLC and an indication for mediastinal staging with at least one lymph node > 1 cm in diameter. Patients with negative or uninformative EBUS-TBNA and positron-emission tomography-positive or -negative nodes, respectively, underwent either mediastinoscopy or surgery. Direct costs related to final diagnosis of node status were prospectively recorded.

Sixteen of 22 participating centers were certified by the EBUS-TBNA–training program and enrolled 163 patients in Step 2. EBUS-TBNA was informative for 149 (91%) patients (75 malignant, 74 non-malignant) and uninformative for 14 (9%). Mediastinoscopy was avoided for 80% of the patients. With a 52% malignant-node rate, EBUS-TBNA positive- and negative-predictive values, respectively, were 100% and 90%. EBUS-TBNA was cost-effective, with expected savings of €1,450 per patient, and would have remained cost-effective even if all EBUS-TBNAs had been performed under general anesthesia or the cost of the procedure had been 30% higher (expected cost-saving of €994 and €1,427 per patient, respectively).

After EBUS-TBNA training and certification of participating centers, the results of this prospective multicenter study confirmed EBUS-TBNA cost-effectiveness for NSCLC staging.

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<![CDATA[Assessing the prognostic factors, survival, and recurrence incidence of triple negative breast cancer patients, a single center study in Iran]]> https://www.researchpad.co/article/5c390bd8d5eed0c48491ea0e

Background

Breast cancer is the second leading cause of death due to cancer in women. Triple negative breast cancer (TNBC) is a subgroup with unique behavior. There is a controversy in organ involvement in metastasis. In this study, we planned to define the prognostic factors, survival, and recurrence incidence of patients.

Materials and method

Among the 583 patients with breast mass referred to hematology and oncology clinic in Shariati hospital, Tehran, Iran from March 2005 to March 2015, fifty four patients entered the survival analysis whom we followed for two years until March 2017. Overall survival (OS) and disease-free survival (DFS) and Cumulative recurrence incidences (RI) were estimated. Univariate and multivariate Cox proportional hazards regression was performed to assess risk factors in predicting OS and DFS.

Results

Median follow up for the patients was 5.00 years. The five-year OS, DFS and RI were 86.13% (95% CI (71.42–93.59), 63.09% (95% CI (47.04–75.49) and 32.15% (95% CI (19.52–47.43) respectively. Among the factors studied OS, DFS and RI differed significantly only between patients with and without nodal involvement (P = 0.004, P = 0.003, and P = 0.02 respectively). On the other hand, based on the univariate modeling, patients with nodal involvement had a higher risk of breast cancer-specific death (HR: 17.99, P = 0.004). Furthermore, patients with nodal involvement had a higher risk of breast cancer-specific death or recurrence (HR = 5.64, P = 0.008). In Multivariate model, just the nodal involvement significantly changed the hazard for OS (HR = 23.91, P = 0.001). As the nodal involvement was the only significant risk factor at the 0.2 level of significance, we can consider the hazard ratio of lymph node positivity in DFS univariate models as adjusted hazard.

Conclusion

The only factor with significant effect on OS, DFS and RI was nodal involvement in the pathology report.

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<![CDATA[Decomposing the subclonal structure of tumors with two-way mixture models on copy number aberrations]]> https://www.researchpad.co/article/5c1ab82fd5eed0c4840270cf

Multistage tumorigenesis is a dynamic process characterized by the accumulation of mutations. Thus, a tumor mass is composed of genetically divergent cell subclones. With the advancement of next-generation sequencing (NGS), mathematical models have been recently developed to decompose tumor subclonal architecture from a collective genome sequencing data. Most of the methods focused on single-nucleotide variants (SNVs). However, somatic copy number aberrations (CNAs) also play critical roles in carcinogenesis. Therefore, further modeling subclonal CNAs composition would hold the promise to improve the analysis of tumor heterogeneity and cancer evolution. To address this issue, we developed a two-way mixture Poisson model, named CloneDeMix for the deconvolution of read-depth information. It can infer the subclonal copy number, mutational cellular prevalence (MCP), subclone composition, and the order in which mutations occurred in the evolutionary hierarchy. The performance of CloneDeMix was systematically assessed in simulations. As a result, the accuracy of CNA inference was nearly 93% and the MCP was also accurately restored. Furthermore, we also demonstrated its applicability using head and neck cancer samples from TCGA. Our results inform about the extent of subclonal CNA diversity, and a group of candidate genes that probably initiate lymph node metastasis during tumor evolution was also discovered. Most importantly, these driver genes are located at 11q13.3 which is highly susceptible to copy number change in head and neck cancer genomes. This study successfully estimates subclonal CNAs and exhibit the evolutionary relationships of mutation events. By doing so, we can track tumor heterogeneity and identify crucial mutations during evolution process. Hence, it facilitates not only understanding the cancer development but finding potential therapeutic targets. Briefly, this framework has implications for improved modeling of tumor evolution and the importance of inclusion of subclonal CNAs.

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<![CDATA[Characterization of T cell receptors in a novel murine model of nickel-induced intraoral metal contact allergy]]> https://www.researchpad.co/article/5c215186d5eed0c4843fa95f

Nickel is a component of several alloy types that are widely used in our environment, including several dental alloy types that cause intraoral metal contact allergy. However, metal-specific immune responses in the oral mucosa have not been elucidated because a suitable animal model has not been established. In this study, we established a novel murine model of nickel-induced intraoral metal contact allergy and aimed to elucidate the immune response in terms of T-cell receptor repertoire and cytokine profiles in inflamed oral mucosa. The intraoral metal contact allergy model was induced by two sensitizations of nickel plus lipopolysaccharide solution into the postauricular skin followed by a single nickel challenge of the buccal mucosa. Cytokine expression profiles and T-cell phenotypes were determined by quantitative polymerase chain reaction. T cells accumulated in the cervical lymph nodes and inflamed oral mucosa were characterized by analyzing their T-cell receptor α- and β-chain repertoires, and the nucleotide sequences of complementary determining region 3. Significant swelling and pathological features were histologically evident at 1 day after challenge in mice with nickel allergy. At 1 day after the challenge, CD8-positive T cells producing high levels of T helper 1 type cytokines had accumulated in the allergic oral mucosa. At 7 days after the challenge, excessive nickel allergy in the oral mucosa was suppressed by regulatory T cells. Characterization of the T-cell receptor repertoire in nickel allergic mice revealed the presence of natural killer T cells and T cells bearing Trav6-6-Traj57 at 1 day after the challenge. Our murine model of nickel-induced intraoral metal contact allergy showed that natural killer T cells and T cells bearing Trav6-6-Traj57 might be involved in the immune responses of nickel-induced intraoral metal contact allergy.

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