METASTATIC ABSCESSES and metastatic tumors can appear in locations that do not seem to be in line of direct spread from their primary focus. There is even a regularity of distribution of these paradoxic metastases. Empirically, the roentgenologist makes a diagnosis of primary carcinoma of the prostate when he finds a certain peculiar distribution of bone lesions in the pelvis. Adequate explanation has not been forthcoming for. the typical and peculiar distribution of these metastatic lesions. The pattern, to me, is not at all that of the nerve sheaths of the area as suggested by Warren, et al.1 It is not the pattern of lymph vessel distribution. The only anatomic system into which this pattern fits is the system of veins which, in its plexiform ramifications, infiltrates and invests the sacrum, the lumbar spine, and the adjacent wings of the ilia. Several years ago, I suggested that the architecture of this plexus of veins could be explored by taking advantage of the pelvic anastomoses of the deep dorsal vein of the penis. The connections and the collateral circulations of this vein are identical with those of the prostatic plexus of veins with which it connects. Valves in the veins of this region are exceedingly variable. All valves present permit flow toward the sacral venous plexus. Injections were first made in I937. A preliminary report was read before the Conference of Eastern Radiologists, in Philadelphia, January 29, I938, under the title of \"The Veins of the Sacrum in Relation to Metastatic Carcinoma from the Prostate.\" This work has been continued and extended. Injections and corrosion preparations of the vessels of the head and neck, already completed, formed an invaluable background for this study. The dissemination of infections and tumors from organs in other regions by the veins about the spine has also been considered. This has led to a better appreciation of the role of the vertebral veins in normal physiology.

The function of the vertebral veins and their role in the spread of metastases : Skeletal cancer metastasis recent expansion of orthopaedic expertise

Neutrophils have a traditional role in inflammatory process and act as the first line of defense against infections. Although their contribution to tumorigenesis and progression is still controversial, accumulating evidence recently has demonstrated that tumor-associated neutrophils (TANs) play a key role in multiple aspects of cancer biology. Here, we detected that chemokine CXCL1 was dramatically elevated in serum from 3LL tumor-bearing mice. In vitro, 3LL cells constitutively expressed and secreted higher level of CXCL1. Furthermore, knocking down CXCL1 expression in 3LL cells significantly hindered tumor growth by inhibiting recruitment of neutrophils from peripheral blood into tumor tissues. Additionally, tumor-infiltrated neutrophils expressed higher levels of MPO and Fas/FasL, which may be involved in TAN-mediated inhibition of CD4(+) and CD8(+) T cells. These results demonstrate that tumor-derived CXCL1 contributes to TANs infiltration in lung cancer which promotes tumor growth.

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Tumor-Derived CXCL1 Promotes Lung Cancer Growth via Recruitment of Tumor-Associated Neutrophils

Recently, several immune checkpoint inhibitors have been developed and are being used to treat malignant melanoma, lung cancer, and other cancers. Several reports have indicated that tumor-infiltrating lymphocytes (TILs) are associated with clinical and histopathologic risk factors in various cancers. However, the role of TILs in esophageal squamous cell carcinoma (ESCC) has not been well studied. This study aimed to investigate the perilesional status of TILs in ESCC and to show associations between TILs and clinical variables. The study enrolled 277 ESCC patients. Evaluation of TILs was performed according to the criteria of the International TILs Working Group 2014, and associations between TIL and clinicopathologic variables were examined. Most of the clinicopathologic factors were not statistically associated with TIL status. The number of patients who received adjuvant therapy was significantly larger in the TIL-negative group. Cancer-specific survival (CSS) of patients in the TIL-positive group was significantly better than in the TIL-negative group. Among the patients who received adjuvant therapy, CSS was significantly better in the TIL-positive group than in the TIL-negative group. Uni- and multivariate analyses identified tumor depth and TIL status as independent prognostic factors for CSS. Among the other clinicopathologic variables, TIL status was the strongest CSS indicator. Tumor-infiltrating lymphocyte status is a strong predictor of good prognosis for ESCC patients.

Clinical Impact of Tumor-Infiltrating Lymphocytes in Esophageal Squamous Cell Carcinoma

Background 
The absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute monocyte count (AMC) and neutrophil to lymphocyte ratio (NLR) are known markers of inflammation. We evaluated whether ANC, ALC, AMC and NLR, both before and after treatment with nivolumab, are indicative markers of overall survival (OS) and evaluated change in NLR as a predictive marker of response in non -small cell lung cancer (NSCLC) patients treated with nivolumab.


Methods 
A total of 109 patients with advanced NSCLC treated with nivolumab were included. ANC, ALC, AMC and NLR were examined at initiation of nivolumab therapy and after two cycles. The prognostic role of ANC, ALC, AMC and NLR with OS and changes in NLR ratio were examined with Kaplan-Meier curves and proportional hazard model.


Result 
Post-treatment NLR ≥5 after two cycles of nivolumab was associated with poor OS (median OS in NLR = <5 vs NLR = ≥5 was 29.1 (16.2–40.9) vs 24.2(16.1–36.2) months respectively, p<0.001). In addition NLR increased in non-responders after two cycles of nivolumab by 6.6±21.8 as compared to responders (p = 0.027).


Conclusions 
Post-treatment ANC, ALC and NLR are independent prognostic factors in NSCLC patients treated with nivolumab. Changes in NLR can be an early biomarker for response in NSCLC patients treated with nivolumab.

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Post-treatment changes in hematological parameters predict response to nivolumab monotherapy in non-small cell lung cancer patients

The role of platelet-to-lymphocyte ratio (PLR) in the prognosis of hepatocellular carcinoma (HCC) patients with different Barcelona Clinic Liver Cancer (BCLC) stages remains controversial. This systematic review and meta-analysis aimed to determine the efficacy of PLR on HCC prognosis. Five electronic databases were searched for clinical trials focusing on the role of PLR in the prognosis of HCC. A total of 297 potential studies were initially identified, and 9 studies comprising 2449 patients were finally enrolled to evaluate the association between the pretreatment PLR and clinical outcomes of overall survival (OS), disease-free survival (DFS), and event occurrence in patients with HCC in different BCLC stages. An elevated pretreatment PLR indicated unfavorable worse OS (HR = 1.73; 95% CI: (1.46, 2.04); ) and DFS (HR = 1.30; 95% CI: (1.06, 1.60); ). Subgroup analysis indicated that high PLR indicated poor OS among BCLC-B/C patients without heterogeneity, while PLR in BCLC-A patients indicated high statistical heterogeneity with value of 78%. As for the correlation between PLR and event occurrence, high PLR was related to poor clinical event occurrence only among BCLC-C patients, though obvious heterogeneity was observed in all different BCLC stages. In conclusion, PLR may be a significant biomarker in the prognosis of HCC in different BCLC stages.

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Prognostic Role of Platelet-to-Lymphocyte Ratio in Hepatocellular Carcinoma with Different BCLC Stages: A Systematic Review and Meta-Analysis

Background Studies suggest that tumour-infiltrating lymphocytes (TILs) and inflammation markers have independent roles in non-small cell lung cancer (NSCLC), but the relationship between the two pronostic factors remains unclear. In this study, we investigated TILs and inflammation markers in with patients advanced stage NSCLC and assessed the association of their levels with prognosis. Materials and methods TILs were evaluated by immunohistochemical staining for cluster of differentiation 3 (CD3) and cluster of differentiation 5 (CD5) and by hematoxylin and eosin staining for non-specific lymphocyte. We investigated the localisation pattern of TILs in advanced stage NSCLC. We divided all cases into two groups: TILs-high and TILs-low groups, by 75th percentile of the population of. In our study, inflammation markers were assessed by C-reactive protein (CRP) and the neutrophil-to-lymphocyte ratio (NLR). Results The results showed that the presence of intra-tumoral high CD3+ and low CD5+ were an independent prognostic factor for overall survival (respectively, P = 0.022 and P = 0.025). Moreover, the high NLR and serum high CRP levels were associated with poor survival (respectively, P = 0.008; P = 0.027). In multi-variate survival analysis, the high CD3+ , low CD5+ , high NLR, tumour node metastasis (TNM) stage, depth of tumour invasion and lymph node metastasis remained independent prognostic factors (respectively, P = 0.018, P = 0.020, P = 0.024, P = 0.038, P = 0.020 and P = 0.047).The high NLR was detected negative correlation with intra-tumoral CD3+ and positive correlation with intra-tumoral CD5+ (respectively, r = -0.623, P = 0.012; r = 0.628, P = 0.028). Conclusions This study is first report demonstrating the prognostic value of intra-tumoral low CD5+ with NSCLC. Increased CD3+ and low CD5+ was observed in patients with poor prognosis; the two molecules were correlated with NLR, suggesting that inflammation might be used as improve therapeutic efficacy to immunotherapy for advanced NSCLC.

Association of intra-tumoral tumour-infiltrating lymphocytes and neutrophil-to-lymphocyte ratio is an independent prognostic factor in non-small cell lung cancer.

Objective: Metastatic tumors of the mandible are rare and usually present clinically as growths. The prognosis of lung cancer patients with bone metastases is poor. Case Report: This article shows a metastasis from adenocarcinoma of the lung affecting the mandible of a 75-year-old female patient where the metastatic lesion was detected before primary tumor. The patient were treated with radiation ther apy with palliative and antalgic intent. But the patient died 8 weeks after the diagnosis. Conclusion: Radiation therapy was effective and well tolerated in the case. Bone metastases particularly mandible metastasis of lung cancer has poor prognosis. Palliative and supportive therapy may be firstly chose because of poor prognosis. Key word: Mandible metastases, Lung cancer, Prognosis

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Mandible bone metastases secondary to pulmonary adenocarcinoma.

Book Citations: Authors, Title, HemaSphere, 2022;6:(S3):pages. The individual abstract DOIs can be found at https://journals.lww.com/hemasphere/pages/default.aspx. Disclaimer: Articles published in the journal HemaSphere exclusively reflect the opinions of the authors. The authors are responsible for all content in their abstracts including accuracy of the facts, statements, citing resources, etc.

P1389: ruxolitinib demonstrates a greater corticosteroid-sparing effect than best available therapy in patients with corticosteroid-refractory/dependent chronic graft-vs-host disease

Sedat Gunes

Papers

Association of intra-tumoral tumour-infiltrating lymphocytes and neutrophil-to-lymphocyte ratio is an independent prognostic factor in non-small cell lung cancer.

Mandible bone metastases secondary to pulmonary adenocarcinoma.

P1389: ruxolitinib demonstrates a greater corticosteroid-sparing effect than best available therapy in patients with corticosteroid-refractory/dependent chronic graft-vs-host disease