Therapeutic Anticoagulation Impacts MR Morphologic Recurrence Patterns in Glioblastoma—A Matched-Pair Analysis

Background: Glioblastoma (GBM) patients are at particularly high risk for thrombotic complications. In the event of a postoperative pulmonary embolism, therapeutic anticoagulation (tAC) is indispensable. The impact of therapeutic anticoagulation on recurrence pattern in GBM is currently unknown. Methods: We conducted a matched-pair cohort analysis of 57 GBM patients with or without tAC that were matched for age, sex, gross total resection and MGMT methylation status in a ratio of 1:2. Patients’ characteristics and clinical course were evaluated using medical charts. MRI characteristics were evaluated by two independent authors blinded to the AC status. Results: The morphologic MRI appearance in first GBM recurrence showed a significantly higher presence of multifocal, midline crossing and sharp demarcated GBM recurrence patterns in patients with therapeutic tAC compared to the matched control group. Although statistically non-significant, the therapeutic tAC cohort showed increased survival. Conclusion: Therapeutic anticoagulation induced significant morphologic changes in GBM recurrences. The underlying pathophysiology is discussed in this article but remains to be further elucidated.

The effect of the low stromal ratio induced by neoadjuvant chemotherapy on recurrence patterns in borderline resectable pancreatic ductal adenocarcinoma

The optimal regimens of neoadjuvant chemotherapy (NAC) and its biological and physiological modification of the tumor microenvironment (TME) in patients with borderline resectable pancreatic ductal adenocarcinoma (BR PDAC) remain unknown. A deeper understanding of the complex stromal biology of the TME will identify new avenues to establish treatment strategies for PDAC patients. Herein, we sought to clarify whether stromal remodeling by NAC affects recurrence patterns and prognosis in BR PDAC patients. We retrospectively analyzed data from 104 BR PDAC patients who underwent pancreatectomy with or without NAC (upfront surgery [UpS], n = 44; gemcitabine + nab-paclitaxel [GnP], n = 28; and gemcitabine + S-1 [GS], n = 32) to assess the correlations of treatment with early recurrence, the stromal ratio, and Ki-67 levels. Eighty-six patients experienced recurrence, and those with liver metastasis had significantly shorter recurrence-free survival than those with other recurrence patterns. The frequency of liver metastasis was significantly higher in patients with a low stromal ratio than in those with a high stromal ratio in the NAC group but not in the UpS group. Patients in the GnP group had significantly higher Ki-67 than those in the GS and UpS groups. A low stromal ratio was positively correlated with high Ki-67 in the NAC group but not in the UpS group. The low stromal ratio induced by NAC promoted early liver metastasis in patients with BR PDAC. Our findings provide new insights into the complexity of stromal biology, leading to consideration of the optimal NAC regimen.

P-OGC65 Patterns and timing of recurrence following resection of oesophago-gastric adenocarcinoma

Background Recurrence following resection of oesophago-gastric adenocarcinoma (OGA) is frequent and associated with poor outcomes. Predictors of site, timing and mechanisms driving recurrence is poorly defined, which limits the development of anti-metastatic agents. The aim of this study was to investigate the patterns and timing of recurrence following resection of OGA. Methods Retrospective review of a prospectively maintained resection database from the Glasgow Royal Infirmary oesophago-gastric unit of patients undergoing surgery for OGA. Primary outcomes were recurrence and cancer specific death following surgery. Recurrence patterns were defined as liver, lung, peritoneal, locoregional only and other distant groups. The latter is a heterogenous group that do not include any liver, lung, or peritoneal metastases. Results N = 635 patients were identified having undergone surgical resection of OGA. Of these, n = 262 developed confirmed recurrent disease. Liver metastases (n = 86, 33%) were the most common site of recurrence, followed by peritoneal (n = 35, 13%), lung (n = 33, 13%) locoregional only (n = 51, 20%) and other distant sites (n = 57, 22%). Liver recurrence was associated with significantly worse disease specific (19.1 vs 28.2 months, P < 0.001) and recurrence free survival (P = 0.006). There was no association between site of recurrence and known prognostic clinicopathological factors, including anaerobic threshold (P = 0.810), nodal status (P = 0.088), pathological T-stage (P = 0.357), differentiation (P = 0.195), deprivation index (P = 0.996), perineural (P = 0.475) or lymphovascular (P = 0.422) invasion. Conclusions Liver metastases is the most common site of recurrence following surgery for OGA. Prognostic clinical and pathological factors do not determine the site of recurrence, suggesting that molecular features of the primary tumour determine and promotes recurrence patterns. Further study to delineate the molecular and microenvironment factors driving recurrence patterns is urgently required.

Patterns of recurrence according to the extent of resection in patients with IDH–wild-type glioblastoma: a retrospective study

OBJECTIVE In glioblastoma (GBM) patients, controlling the microenvironment around the tumor using various treatment modalities, including surgical intervention, is essential in determining the outcome of treatment. This study was conducted to elucidate whether recurrence patterns differ according to the extent of resection (EOR) and whether this difference affects prognosis. METHODS This single-center study included 358 eligible patients with histologically confirmed isocitrate dehydrogenase (IDH)–wild-type GBM from November 1, 2005, to December 31, 2018. Patients were assigned to one of three separate groups according to EOR: supratotal resection (SupTR), gross-total resection (GTR), and subtotal resection (STR) groups. The patterns of recurrence were classified as local, marginal, and distant based on the range of radiation. The relationship between EOR and recurrence pattern was statistically analyzed. RESULTS Observed tumor recurrence rates for each group were as follows: SupTR group, 63.4%; GTR group, 75.3%; and STR group, 80.5% (p = 0.072). Statistically significant differences in patterns of recurrences among groups were observed with respect to local recurrence (SupTR, 57.7%; GTR, 76.0%; STR, 82.8%; p = 0.036) and distant recurrence (SupTR, 50.0%; GTR, 30.1%; STR, 23.2%; p = 0.028). Marginal recurrence showed no statistical difference between groups. Both overall survival and progression-free survival were significantly increased in the SupTR group compared with the STR and GTR groups (p < 0.0001). CONCLUSIONS In this study, the authors investigated the association between EOR and patterns of recurrence in patients with IDH–wild-type GBM. The findings not only show that recurrence patterns differ according to EOR but also provide clinical evidence supporting the hypothesized mechanism by which distant recurrence occurs.

Recurring Lexis and Reader-Reception in Horace’s Odes: The Formation of a Lyric Opus

<p>This study investigates perceived patterns of lexical recurrence in consecutive or closely proximate poems in Books 1-3 of the Odes of the Roman poet Horace and considers the significance these may have for the structure and organization of this work and its interpretive reception by readers. An initial discussion and demonstration of the types of lexical recurrence observed and their frequency prompts the question of the extent to which these recurrent lexical usages are intentional on the part of the author and hence whether they were factors in determining the order in which the poems of each book are arranged. This question is investigated firstly through statistical analysis, which shows that there is no statistically significant greater clustering effect apparent in the lexical patterns observed than had the odes been arranged in random order. Nevertheless, given than certain recurrences between closely adjacent poems do stand out because of the identity or close similarity of their grammatical or morphological forms and/or metrical location, and that this phenomenon has been perceived by other commentators, the significance that might be attributed to these as poetic effects falls within the domain of reader-reception theory. A summary review of the principal tenets of this theory as developed especially by Ingarden, Gadamer, Jauss and Iser is undertaken in order to derive a sound theoretical method by which the recurrence patterns may be analysed and coherent meaning may be constructed from them. This method is then applied to analysis of a prominent cluster of lexical recurrences over the final five poems of Odes 1 (1.34-1.38). The question of how far such meaning may have corresponded to the intentions of the author Horace is then addressed. A distinction is made, following Bakhtin, between the “primary”, historical author who composed the work and the “secondary” authorial consciousness who engages the reader through the text. While intentions of the former are ultimately unknowable, the secondary author “Horace” does declare intentions for his work through his texts which the reader may then reconstruct. The thesis posits that the poetic ambition of Horace within this textual horizon was first to acquire an erudite and discerning audience capable of accepting him and appreciating his artistry, and then to develop a distinctive generic vehicle by which to engage this audience in dialogue about matters of importance in the Roman social, political and cultural worlds. The development of an audience is a major theme of his Satires Book 1, while the book of Epodes is the framework for his attempt to adapt the iambic metre of Archilochus to his dialogic purpose. The analysis shows that this latter project proved unfruitful because of the indelible association of iambic with invective. The concluding chapter shows that it was the adoption of archaic Greek lyric metres other than iambic that finally provided Horace with the poetic vehicle he sought to write verse that both adhered to the Callimachean aesthetic of brevity and technical perfection and allowed engagement with serious as well as frivolous themes. It examines the manner by which the three Books of Odes, read sequentially as a single opus, firstly familiarize their readers with these archaic metres and the range of lyric themes they can encompass before leading them to an acceptance that lyric can also address important public issues, notably in the “Roman Odes” of Book 3. The perception of the patterns of lexical recurrence throughout the three books is a significant factor in promoting this dialogic engagement of the reader with the text.</p>

Recurring Lexis and Reader-Reception in Horace’s Odes: The Formation of a Lyric Opus

<p>This study investigates perceived patterns of lexical recurrence in consecutive or closely proximate poems in Books 1-3 of the Odes of the Roman poet Horace and considers the significance these may have for the structure and organization of this work and its interpretive reception by readers. An initial discussion and demonstration of the types of lexical recurrence observed and their frequency prompts the question of the extent to which these recurrent lexical usages are intentional on the part of the author and hence whether they were factors in determining the order in which the poems of each book are arranged. This question is investigated firstly through statistical analysis, which shows that there is no statistically significant greater clustering effect apparent in the lexical patterns observed than had the odes been arranged in random order. Nevertheless, given than certain recurrences between closely adjacent poems do stand out because of the identity or close similarity of their grammatical or morphological forms and/or metrical location, and that this phenomenon has been perceived by other commentators, the significance that might be attributed to these as poetic effects falls within the domain of reader-reception theory. A summary review of the principal tenets of this theory as developed especially by Ingarden, Gadamer, Jauss and Iser is undertaken in order to derive a sound theoretical method by which the recurrence patterns may be analysed and coherent meaning may be constructed from them. This method is then applied to analysis of a prominent cluster of lexical recurrences over the final five poems of Odes 1 (1.34-1.38). The question of how far such meaning may have corresponded to the intentions of the author Horace is then addressed. A distinction is made, following Bakhtin, between the “primary”, historical author who composed the work and the “secondary” authorial consciousness who engages the reader through the text. While intentions of the former are ultimately unknowable, the secondary author “Horace” does declare intentions for his work through his texts which the reader may then reconstruct. The thesis posits that the poetic ambition of Horace within this textual horizon was first to acquire an erudite and discerning audience capable of accepting him and appreciating his artistry, and then to develop a distinctive generic vehicle by which to engage this audience in dialogue about matters of importance in the Roman social, political and cultural worlds. The development of an audience is a major theme of his Satires Book 1, while the book of Epodes is the framework for his attempt to adapt the iambic metre of Archilochus to his dialogic purpose. The analysis shows that this latter project proved unfruitful because of the indelible association of iambic with invective. The concluding chapter shows that it was the adoption of archaic Greek lyric metres other than iambic that finally provided Horace with the poetic vehicle he sought to write verse that both adhered to the Callimachean aesthetic of brevity and technical perfection and allowed engagement with serious as well as frivolous themes. It examines the manner by which the three Books of Odes, read sequentially as a single opus, firstly familiarize their readers with these archaic metres and the range of lyric themes they can encompass before leading them to an acceptance that lyric can also address important public issues, notably in the “Roman Odes” of Book 3. The perception of the patterns of lexical recurrence throughout the three books is a significant factor in promoting this dialogic engagement of the reader with the text.</p>