Linking tumor immune infiltrate and systemic immune mediators to treatment response and prognosis in advanced cervical cancer.

Cervical cancer (CC) poses a significant burden on individuals in developing regions, exhibiting heterogeneous responses to standard chemoradiation therapy, and contributing to substantial mortality rates. Unraveling host immune dynamics holds promise for innovative therapies and discovery of clinically relevant biomarkers. We studied prospectively locally advanced CC patients pre-treatment, stratifying them as responders (R) or non-responders (NR). R patients had increased tumor-infiltrating lymphocytes (TILs), while NR patients showed elevated PD-1 scores, CD8+ and PD-L2+ TILs, and PD-L1 immune reactivity. NR patients exhibited higher systemic soluble mediators correlating with TIL immune markers. R patients demonstrated functional polarization of CD4 T cells (Th1, Th2, Th17, and Treg), while CD8+ T cells and CD68+ macrophages predominated in the NR group. Receiver operating characteristic analysis identified potential CC response predictors, including PD-L1-immunoreactive (IR) area, PD-L2, CD8, FGF-basic, IL-7, IL-8, IL-12p40, IL-15, and TNF-alpha. Dysfunctional TILs and imbalanced immune mediators contribute to therapeutic insufficiency, shedding light on local and systemic immune interplay. Our study informs immunological signatures for treatment prediction and CC prognosis.

Cervical Cancer Stem-Like Cell Transcriptome Profiles Predict Response to Chemoradiotherapy.

Cervical cancer (CC) represents a major global health issue, particularly impacting women from resource constrained regions worldwide. Treatment refractoriness to standard chemoradiotheraphy has identified cancer stem cells as critical coordinators behind the biological mechanisms of resistance, contributing to CC recurrence. In this work, we evaluated differential gene expression in cervical cancer stem-like cells (CCSC) as biomarkers related to intrinsic chemoradioresistance in CC. A total of 31 patients with locally advanced CC and referred to Mário Penna Institute (Belo Horizonte, Brazil) from August 2017 to May 2018 were recruited for the study. Fluorescence-activated cell sorting was used to enrich CD34+/CD45- CCSC from tumor biopsies. Transcriptome was performed using ultra-low input RNA sequencing and differentially expressed genes (DEGs) using Log2 fold differences and adjusted p-value < 0.05 were determined. The analysis returned 1050 DEGs when comparing the Non-Responder (NR) (n=10) and Responder (R) (n=21) groups to chemoradiotherapy. These included a wide-ranging pattern of underexpressed coding genes in the NR vs. R patients and a panel of lncRNAs and miRNAs with implications for CC tumorigenesis. A panel of biomarkers was selected using the rank-based AUC (Area Under the ROC Curve) and pAUC (partial AUC) measurements for diagnostic sensitivity and specificity. Genes overlapping between the 21 highest AUC and pAUC loci revealed seven genes with a strong capacity for identifying NR vs. R patients (ILF2, RBM22P2, ACO16722.1, AL360175.1 and AC092354.1), of which four also returned significant survival Hazard Ratios. This study identifies DEG signatures that provide potential biomarkers in CC prognosis and treatment outcome, as well as identifies potential alternative targets for cancer therapy.

18F-FDG PET/CT as a prognostic factor in penile cancer.

PURPOSE: Penile cancer (PC) is a rare neoplasm with an aggressive behavior and variable prognosis. Lymph node (LN) involvement and pathological features of the primary lesion have been proven to be the most important survival factors. Positron emission tomography/computed tomography with fluorodeoxyglucose labelled with fluorine-18 (18F-FDG PET/CT) provides information on tumor staging and works as a prognostic factor, with promising results in other carcinomas. The aim of the present study is to evaluate PET/CT as a prognostic factor in PC. METHODS: Fifty-five patients (mean age 56.6 y) diagnosed with penile squamous cell carcinoma were prospectively evaluated from 2012 to 2014. All subjects underwent 18F-FDG PET/CT before treatment and were regularly followed after surgery. RESULTS: Out of the 53 patients selected, 17 (32.1%) had localized disease (cT1-2) and 24 (45.3%) had palpable nodes (cN+). Partial penile amputation was performed in 38 patients (71.7%) and inguinal lymphadenectomy (LND) in 30 (56.6%). From the LND group, 16 (53.3%) presented with positive neoplastic cells (pN+). Patients with more aggressive disease had a significantly (p = 0.019) higher 18F-FDG tumor uptake (pSUVmax), while inguinal LN uptake (nSUVmax) was able to recognize metastatic LN (p = 0.039). Some pathological prognostic features, when presented, have shown significant changes in pSUVmax values. Receiver operating characteristic (ROC) curves were performed and specific cutoff values of pSUVmax were evaluated to determine sensitivity and specificity. Regarding regional LNs, PET/CT presented a 76.2% accuracy in cN+ patients. After a 39-month follow up, pSUVmax of 16.6 (p = 0.0001) and nSUVmax of 6.5 (p = 0.019) were established as the ideal values to predict cancer-specific survival. The multivariate analysis confirmed nSUVmax as a predictor for LN metastasis (p = 0.043) and pSUVmax as a mean to estimate survival rate (p = 0.05). CONCLUSION: This study showed promising results on the use of 18F-FDG PET/CT as a prognostic tool for PC, using specific cutoff values of pSUVmax and nSUVmax.

Invasão do duodeno por carcinoma do terço distal do estômago: estudo histopatológico e revisão da literatura / Distal gastric carcinoma with duodenal invasion: histopathologic study and literature review

Gastric carcinoma with duodenal invasion is reported in 11 per cent to 33.3 per cent of surgical specimens. In spite of this high frequency, it is not easily recognised during the surgical proceeding or at gross examination. The study of risk factors like histological type, tumor stage and extension of duodenal invasion can be useful in establishing the best surgical approach in order to diminish the risk of local recurrence. We report 50 cases of distal gastric carcinoma in which we analysed the tumor extension in the different layers of the duodenal wall; duodenal invasion was correlated with histological type, level of infiltration in the gastric wall and presence of vascular invasion. Duodenal invasion was observed in 27 cases (54 per cent), 17/32 of intestinal type (53 per cent), 9/10 of diffuse type (90 per cent) e 1/8 of non-classifiable tumours (12.5 per cent). Diffuse type carcinoma was the most important risk factor for invasion (OR = 11; CI 95 per cent: 1.20 to 254.16; P < 0.01). Most of the cases (21/27, 77 per cent) were stage III or IV. The submucosal layer was the most frequent (22/27 cases, 81per cent) and also most extensively (8.21 +/- 9.75 mm) invaded. We conclude that the risk of duodenal invasion is higher in diffuse type tumours and in stage III or IV. Distal surgical resection should be wider in these cases and determined by frozen section biopsy specimen at the point of transection

Schwannoma nasal com extensäo intracraniana: relato de caso / Nasal schwannoma with intracranial extension: case report

Os autores relatam caso raro de schwannoma nasal com invasäo intracraniana no Serviço de Otorrinolaringologia do Hospital das Clínicas da UFMG - Universidade Federal de Minas Gerais. Discutem-se aspectos como freqüência, patogênese, apresentaçäo clínica, achados histopatológicos e imuno-histoquímicos e fazem-se consideraçöes sobre propostas de intervençäo observadas na literatura, destacando a abordagem exclusivamente por microcirurgia endonasal