Significant Negative Prognostic Factor Research Articles

Impact of age on surgical outcomes for world federation of neurosurgical societies grade I and II aneurysmal subarachnoid haemorrhage: a novel prognostic model using recursive partitioning analysis

This study aimed to evaluate age as a prognostic factor and develop a comprehensive prognostic model for patients undergoing clipping surgery for World Federation of Neurosurgical Societies (WFNS) grade I/II aneurysmal subarachnoid haemorrhage (SAH). We retrospectively investigated 188 patients with WFNS grade I/II SAH who underwent microsurgical clipping at our institute between December 2010 and January 2020. The data of 176 patients (75 with grade I and 101 with grade II) were analysed. Data on patient demographics, aneurysm characteristics, SAH factors, surgical details, and clinical outcomes were collected. Prognostic factors were assessed using bivariate and multivariable logistic regression analyses, and recursive partitioning analysis. Favourable outcomes (mRS 0–2) were observed in 76% of patients. Age, a significant negative prognostic factor in multivariable analysis (odds ratio 0.55, 95% confidence interval 0.40–0.76, p < 0.001), was cutoff at 70 years by the receiver operating characteristic curve. Patients aged ≤ 70 years had significantly better outcomes than those aged > 70 years (84% vs. 46%, respectively; p < 0.001). Epileptic seizures were significantly associated with poor outcomes in older adults (p < 0.001). A prognostic model (favourable, intermediate, and poor) based on age and postoperative adverse events showed significantly different outcomes between age groups (p < 0.001). Age was a stronger prognostic factor than WFNS grading for patients with grade I/II SAH undergoing microsurgical clipping. For patients aged ≤ 70 years, precise microsurgeries with fewer complications were associated with favourable outcomes beyond WFNS grade. For older patients, postoperative intensive seizure management may prevent poor outcomes.

A Real-World Analysis of Oncological Outcomes in Patients with Oral Squamous Cell Carcinoma Requiring Marginal Mandibulectomy for Achieving Clear Surgical Margins

Introduction Marginal mandibulectomy (MM) offers a conservative alternative to segmental resections for patients with oral squamous cell carcinoma (OSCC) requiring clear margins without evident bone invasion. Despite its potential benefits, real-world outcomes related to surgical margins and oncological outcomes have not been studied sufficiently. Methods This ambispective cohort study analyzed 183 patients undergoing MM from January 2015 to March 2021 to achieve clear margins without clinical bone involvement. The primary objective is to assess the disease-free survival (DFS) in patients with OSCC requiring MM to achieve clear surgical margins, and the secondary objective is to assess the impact of microscopic bone involvement on these outcomes. Kaplan–Meier estimates facilitated the survival analysis. Results The cohort primarily comprised males (83.2%) with a median age of 50 years, the predominant subsite being the bucco-alveolar complex (94%). Microscopic bone involvement was found in 8.74% of patients. The distribution of surgical margins was 84.24% negative, 15.22% close, and 0.54% positive. The cohort's 3-year DFS and overall survival (OS) rates are 65 and 70%, respectively. Patients with microscopic bone involvement experienced lower DFS (odds ratio [OR] = 0.251, p = 0.013), and perineural invasion was also a significant negative prognostic factor for DFS (OR = 0.4, p = 0.01). Statistical analyses revealed significant differences in survival distributions based on bone involvement (p = 0.049). Conclusion While MM can achieve favorable surgical margins in selected OSCC patients, microscopic bone involvement compromises DFS. Given the low incidence of bone involvement and high rate of negative margins, more conservative approaches might be justified in select patients. However, these findings require further validation in a larger cohort.

Patient Factors Influencing Outcomes at 12-Year Follow-up of Hip Arthroscopy for Femoroacetabular Impingement

Background: Arthroscopic treatment of femoroacetabular impingement has increased in popularity since the early 2000s when it was first described, although only a few midterm follow-up studies have been published. Purpose: To describe the outcomes of patients undergoing hip arthroscopy for femoroacetabular impingement at a mean 12-year follow-up and to determine the risk factors for failure. Study Design: Case-control study; Level of evidence, 3. Methods: The Non-Arthritic Hip Score (NAHS) and a radiographic evaluation were completed preoperatively and at midterm follow-up. Participants were divided into 2 groups according to their clinical evolution. The success group consisted of patients whose NAHS at the final follow-up was above the established Patient Acceptable Symptom State (PASS) threshold of 81.9, whereas patients who underwent a second surgical intervention or did not reach the PASS threshold at final follow-up were assigned to the failure group. These groups were compared to identify preoperative differences in demographic, pathological, and surgical factors. Results: A total of 95 hips were included, after 23 were lost to follow-up (80.5% follow-up). At a mean follow-up of 12.1 years (range, 9.2-16.0 years), 9 hips required total hip arthroplasty (9.5%), 5 required revision hip arthroscopy (5.3%), 29 did not achieve the NAHS PASS threshold (30.5%), and 52 achieved the NAHS PASS threshold (54.7%). The mean NAHS was 82.4 at final follow-up compared with 66.9 preoperatively (mean difference = 15.5; P < .001). Higher mean body mass index (24.9 vs 23.0; P = .030), older age (30.0 vs 27.2; P = .035), and inferior preoperative lateral joint space width (3.9 vs 4.4; P = .019) were associated with inferior prognosis in the failure group versus success group. Osteoarthritis progression was observed in 69.2% of the failure group and in 34.8% of the success group (P = .082). Labral ossification was observed in 78.3% of all patients, and its lateral projection length was statistically associated with failure (P = .015). Conclusion: At a mean 12-year follow-up, hip arthroscopy for femoroacetabular impingement led to significant clinical improvement, with 55% PASS achievement. In total, 31% of patients were below the PASS threshold, 5% had revision arthroscopy, and only 9% had conversion to total hip arthroplasty for a 45% global failure rate. Increased body mass index, older age, and smaller preoperative lateral joint space width were significant negative prognostic factors. Postoperative degenerative changes were highly prevalent and demonstrated association with failure.

Abstract PO4-05-13: Expression of DLC1/STARD12 and variants in clinical breast cancer and implication in skeletal metastasis

Abstract Introduction: Deleted in Liver Cancer 1 Protein, DLC1, also known as StAR Related Lipid Transfer Domain Containing 12 (StarD12), is a known negative regulator of the Rho GTPases and at the cellular level regulates cell migration. DLC1 gene transcription produces multiple isoforms of the DLC1 protein. The present study examined the clinical and prognostic implications of DLC1 isoforms, DLC1/V1/V2/V3, in relationship with Rho GTPases in human breast cancer. Methods: Expression of three DLC1 isoforms was evaluated in a cohort of breast cancer tissues and against the clinical, pathological and clinical outcome of patients. DLC1 expression was also assessed and compared against Rho GTPases, including Rho and Rho GTP Dissociation Inhibitor (Rho GDI), in the same cohort. Results: DLC1/V3 had a significant impact on the overall survival of patients and high levels were linked to shorter survival (Hazard Ratio=3.551 (95%CI 1.332-9.471, p=0.011), a prediction that was independent of other factors in multivariate analysis. RUC analysis demonstrated a significant predictive value for bone metastasis with DLC1/V3 (RUC=0.714, p=0.020), showing a Hazard ratio of 9.0 (1.8-44.5, p=0.007). Similarly, high DLC1/V2 expression was also linked to a shorter overall survival (p=0.035). DLC1/V2 did not show a significant correlation with bone metastasis. In contrast to V3 and V2 variants, DLC1 had a marginal overall survival benefit for the patients, in that patients with high DLC1 had a longer survival (p=0.056). DLC1/V3 had a contrasting correlation with Rho-A (r=-0.203, p=0.015) and Rho-GDI-G (r=0.194, p=0.019) and the combined expression of DLC1/V3 and RhoA/Rho-GDI-G further identified patients with poorer clinical outcome. Conclusions: DLC1 and its variants have differing impacts on breast cancer; whereas DLC1 appears to be a tumour suppressive molecule, its variant isoform-3 was more oncogenic and a significant negative prognostic factor, together with its regulators Rho and Rho GDI. Citation Format: Binbin Cong, Jane Lane, Xiaoshan Cao, Tracey Martin, Robert E Mansel, Eleri Davies, Wen Jiang. Expression of DLC1/STARD12 and variants in clinical breast cancer and implication in skeletal metastasis [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-05-13.

Survival analysis after stereotactic ablative radiotherapy for early stage non-small cell lung cancer: a single-institution cohort study

BackgroundStereotactic ablative radiotherapy (SABR) is the standard treatment for medically inoperable early-stage non-small cell lung cancer (ES-NSCLC), but which patients benefit from stereotactic radiotherapy is unclear. The aim of this study was to analyze prognostic factors for early mortality.MethodsFrom August 2010 to 2022, 617 patients with medically inoperable, peripheral or central ES-NSCLC were treated with SABR at our institution. We retrospectively evaluated the data from 172 consecutive patients treated from 2018 to 2020 to analyze the prognostic factors associated with overall survival (OS). The biological effective dose was > 100 Gy10 in all patients, and 60 Gy was applied in 3–5 fractions for a gross tumor volume (GTV) + 3 mm margin when the tumor diameter was < 1 cm; 30–33 Gy was delivered in one fraction. Real-time tumor tracking or an internal target volume approach was applied in 96% and 4% of cases, respectively. In uni- and multivariate analysis, a Cox model was used for the following variables: ventilation parameter FEV1, histology, age, T stage, central vs. peripheral site, gender, pretreatment PET, biologically effective dose (BED), and age-adjusted Charlson comorbidity index (AACCI).ResultsThe median OS was 35.3 months. In univariate analysis, no correlation was found between OS and ventilation parameters, histology, PET, or centrality. Tumor diameter, biological effective dose, gender, and AACCI met the criteria for inclusion in the multivariate analysis. The multivariate model showed that males (HR 1.51, 95% CI 1.01–2.28; p = 0.05) and AACCI > 5 (HR 1.56, 95% CI 1.06–2.31; p = 0.026) were significant negative prognostic factors of OS. However, the analysis of OS showed that the significant effect of AACCI > 5 was achieved only after 3 years (3-year OS 37% vs. 56%, p = 0.021), whereas the OS in one year was similar (1-year OS 83% vs. 86%, p = 0.58).ConclusionSABR of ES-NSCLC with precise image guidance is feasible for all medically inoperable patients with reasonable performance status. Early deaths were rare in our real-life cohort, and OS is clearly higher than would have been expected after best supportive care.

Prognostic factors and survival following radiation therapy for canine nasal tumors: A single-institution retrospective study of 166 cases.

Prognostic factors in dogs with nasal tumors include several variables. However, factors that can measure prognosis have not yet been identified due to considerable divergence among reports. To describe the computed tomography (CT) imaging, treatment, and outcomes of dogs with nasal tumors, as well as detect negative prognostic factors through the analysis of a substantial number of cases from a single institution. Furthermore, based on CT findings, this study aimed to identify independent prognostic factors for nasal tumors in dogs. A total of 166 client-owned dogs were diagnosed with nasal tumors at Gifu University Veterinary Hospital between 2015 and 2019. Data were retrospectively collected from the electronic medical records. Univariate analysis revealed a significant difference in survival time between adenocarcinoma and squamous cell carcinoma in 166 canine nasal tumors treated with megavoltage (MeV) radiation therapy at a single institution (p = .015). There was a significant difference in survival time between carcinoma and sarcoma (p = .04). Regarding CT imaging findings, significant differences in survival time were observed for frontal sinus invasion (p = .007), cribriform plate destruction (p < .001), and lymph node metastasis (p = .003). Multivariate Cox regression analysis was performed to assess frontal sinus invasion, cribriform plate destruction, histopathologic subtypes, and lymph node metastasis as negative prognostic factors; however, only cribriform plate destruction was a significant negative prognostic factor for survival time (p = .004). Multivariate Cox regression analysis showed that cribriform plate destruction was the main factor in predicting a negative prognosis among 166 canine nasal tumors treated with MeV radiation therapy at a single institution. Therefore, we propose a new 2-tier staging classification for canine nasal tumors with the presence or absence of cribriform plate destruction based on CT examination as the only evaluation factor.

New Insights on the Importance of the Extent of Vascular Invasion in Widely Invasive Follicular Thyroid Carcinoma.

This study aimed to investigate the association between the extent of vascular invasion (VI) and the outcome of widely invasive follicular thyroid carcinoma (WI-FTC). The records of 107 patients with WI-FTC confirmed by surgical specimens from January 2005 to December 2016 were retrospectively reviewed. Among the 107 patients with WI-FTC, those with a VI of < 4 (n = 62) and ≥ 4 (n = 45) had a 10year cause-specific survival (CSS) rate of 97.7% and 89.4% (p = 0.008), respectively. Univariate analysis identified M1 (p = 0.001), and the number of VI of ≥ 4 as significant negative prognostic factors for CSS. Multivariate analysis identified M1 (hazard ratio [HR] = 9.366) as independent negative prognostic factor for CSS. Among the 72 patients with M0 WI-FTC, those with a VI of < 2 (n = 33) and ≥ 2 (n = 39) had a 10-year distant metastasis-free survival (DMFS) rate of 96.8% and 56.8% (p = 0.001), respectively. Univariate analysis identified age ≥ 55years (p = 0.011), presence of VI, the number of VI of ≥ 2, and resection margin status (p < 0.001) as significant negative prognostic factors for DMFS. Multivariate analysis identified the number of VI ≥ 2 (HR = 9.137), and resection margin status (HR = 5.853) as independent negative prognostic factors for DMFS. It may be unnecessary that WI-FTC with curative resection margin status and a VI of < 2, especially in capsular invasion only, routinely undergo completion thyroidectomy and postoperative ablation.

Metastatic breast cancer in Kenya: survival, prognosis and management at a tertiary referral centre.

There has been an increase in breast cancer in Africa with up to 77% of patients diagnosed with advanced disease. However, there is little data on survival outcomes and prognostic factors affecting survival in patients with metastatic breast cancer (MBC) in Africa. The study objective was to establish the survival of patients with MBC at a single tertiary health facility, the clinical and pathological characteristics affecting survival and describe the treatment modalities used. This was a retrospective descriptive study conducted at Aga Khan University Hospital, Nairobi of patients diagnosed with MBC between 2009 and 2017. Survival data was collected on metastatic free survival, survival time between diagnosis of first metastasis and death and overall survival. Data on patient's age, menopausal status and stage at diagnosis, tumour grade, receptor status, site of metastasis and treatment given was also collected. The Kaplan-Meier Estimator was used to estimate survival. Prognostic factors for survival outcomes were analysed using univariate analysis. Standard descriptive statistics were used to describe patient characteristics. A total of 131 patients were included in the study. The median survival was 22 months. The 3 and 5-year survivals were 31.3% and 10.7%, respectively. On univariate analysis, the Luminal A molecular subtype was a significant positive prognostic factor hazard ratios (HR 0.652 95% confidence interval (CI) 0.473-0.899) while metastasis to the liver or brain were significant negative prognostic factors (HR 0.615 95% CI 0.413-0.915 and HR 0.566 95% CI 0.330-0.973, respectively). A large proportion (87.0%) received some treatment for metastatic disease. Our study concluded that survival rates for patients diagnosed with MBC were lower compared to studies from Western countries but higher than in studies from Sub-Saharan Africa. Luminal A molecular subtype was found to be a positive prognostic factor and metastasis to the liver or brain were found to be negative prognostic factors. Improved access to adequate treatment for MBC is required in the region.

Historical eye on IPF: a cohort study redefining the mortality scenario.

Therapies that slow idiopathic pulmonary fibrosis (IPF) progression are now available and recent studies suggest that the use of antifibrotic therapy may reduce IPF mortality. The aim of the study was to evaluate whether, to what extent, and for which factors the survival of IPF in a real-life setting has changed in the last 15 years. Historical eye is an observational study of a large cohort of consecutive IPF patients diagnosed and treated in a referral center for ILDs with prospective intention. We recruited all consecutive IPF patients seen at GB Morgagni Hospital, Forlì, Italy between January 2002 and December 2016 (15 years). We used survival analysis methods to describe and model the time to death or lung transplant and Cox regression to model prevalent and incident patient characteristics (time-dependent Cox models were fitted). The study comprised 634 patients. The year 2012 identifies the time point of mortality shift (HR 0.58, CI 0.46-0.63, p < 0.001). In the more recent cohort, more patients had better preserved lung function, underwent cryobiopsy instead of surgery, and were treated with antifibrotics. Highly significant negative prognostic factors were lung cancer (HR 4.46, 95% CI 3.3-6, p < 0.001), hospitalizations (HR 8.37, 95% CI 6.5-10.7, p < 0.001), and acute exacerbations (HR 8.37, 95% CI 6.52-10.7, p < 0.001). The average antifibrotic treatment effect estimated using propensity score matching showed a significant effect in the reduction of all-cause mortality (ATE coeff -0.23, SE 0.04, p < 0.001), acute exacerbations (ATE coeff -0.15, SE 0.04, p < 0.001), and hospitalizations (ATE coeff -0.15, SE 0.04, p < 0.001) but no effect on lung cancer risk (ATE coeff -0.03, SE 0.03, p = 0.4). Antifibrotic drugs significantly impact hospitalizations, acute exacerbations, and IPF survival. After the introduction of cryobiopsy and antifibrotic drugs, the prognosis of IPF patients has significantly improved together with our ability to detect IPF at an earlier stage.

Abstract 2205: KRTAP 2-3 is a novel potential biomarker of cells in the polyaneuploid cancer cell (PACC) state to predict cancer recurrence

Abstract Prostate cancer (PCa) is the second leading cause of death in American men. PCa death is primarily attributed to therapeutic resistance. Our group and others have recently discovered a stress-induced adaptive cell state that plays a key role in therapy resistance: the polyaneuploid cancer cell (PACC) state. Cells in the polyaneuploid cancer cell (PACC) state are characterized by large cell size and polyploidization of the baseline aneuploid genome. Cells in the PACC state (e.g., pleomorphic giant cells, polyploid giant cancer cells, osteoclast like cells) have been reported in patient tumor specimens of multiple cancer types. We recently reported that in primary tumor specimens of PCa patients undergoing radical prostatectomy with curative intent, the number of cells in the PACC state is a statistically significant negative prognostic factor for metastasis-free survival (data adjusted for CAPRA-S). These data highlight the promise of the PACC state as a predictive biomarker for recurrence. In our previous work, cells in the PACC state were identified and quantified through EpCAM immunohistochemistry (IHC) to visualize cell membranes, manually including cells with &amp;gt3x increased nuclear area compared to adjacent non-polyploid cancer cells. However, this method is labor intensive and highly subjective. There are currently no biomarkers to distinguish cells in the PACC state. To identify candidate PACC state biomarkers, we performed RNA sequencing to identify differentially expressed genes. Across two independent RNA sequencing datasets of PC3 cells induced to enter the PACC state with IC50 cisplatin or IC90 docetaxel, the most differentially expressed gene was KRTAP2-3 (Log2FC=4.3 and 5.51, respectively). The Keratin Associated Protein 2-3 (KRTAP2-3) is encoded by one of the homologous KRTAP genes classified by high sulfur content and is primarily expressed in the cortex of the hair follicle. It has not been previously implicated in PCa or in chemotherapy resistance. Due to its differential RNA expression in the PACC state and its low expression in most normal tissues, we hypothesize that KRTAP2-3 can be used as a biomarker to distinguish cells in the PACC state in patient tumor samples. To test this directly, we optimized RNA in situ-hybridization (RNAish) for KRTAP2-3. In initial experiments utilizing PC3 cell line plugs, we found that the KRTAP2-3 RNAish signal successfully distinguished cells in the PACC state (50.6 average punctae/cell) from non-polyploid cells (0.19 average punctae/cell) reflecting 96% percent accuracy using sensitivity and specificity metrics. We have further confirmed positive KRTAP2-3 signal on PC3 cells induced to access the PACC state in response to cisplatin, docetaxel, and etoposide treatment. Future work will evaluate the utility of the KRTAP2-3 gene as a prognostic biomarker that marks cells in the PACC state within PCa patient tissue microarrays. Citation Format: Sabrina A. Mendez, Reema Sharma, Kenneth J. Pienta, Sarah R. Amend. KRTAP 2-3 is a novel potential biomarker of cells in the polyaneuploid cancer cell (PACC) state to predict cancer recurrence [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2205.

Clinical Determinants of Extraurinary Tract Recurrence and Survival after Radical Surgery for pT2 Upper Tract Urothelial Carcinoma

Oncologic outcomes for pT2N0M0 upper tract urothelial carcinoma (UTUC) after nephroureterectomy are not well defined, with most previous studies focused on a heterogeneous population. Therefore, we aimed to investigate the clinical determinants of extraurinary tract recurrence and survival after radical surgery in patients with localized UTUC. We retrospectively identified 476 patients with pT2N0M0 UTUC who underwent radical nephroureterectomy or ureterectomy between October 2002 and March 2022. To evaluate the prognostic impact, patients were divided into renal pelvic, ureteral, and both-region (renal pelvis plus synchronous ureter) groups based on tumor location. The outcomes included recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Associations were evaluated using multivariable Cox regression analyses for prognostic factors and Kaplan-Meier analyses for survival curves. The renal pelvic, ureteral, and both-region groups consisted of 151 (31.7%), 314 (66.0%), and 11 (2.3%) patients, respectively. Kaplan-Meier analyses comparing the three tumor types showed significant differences in 5-year RFS (83.6% vs. 73.6% vs. 52.5%, p = 0.013), CSS (88.6% vs. 80.7% vs. 51.0%, p = 0.011), and OS (83.4% vs. 70.1% vs. 45.6%, p = 0.002). Multivariable analyses showed that age >60 years, previous bladder cancer history, ureteral involvement (ureteral and both-regional groups), and positive surgical margins were significant negative prognostic factors for the studied outcomes. Patients with pT2 UTUC and presence of ureteral involvement had more frequent disease relapse. Subsequent adjuvant therapy regimens and close follow-up in patients with negative prognostic factors are warranted despite complete pathological removal of the tumor.

Efficacy and safety of immune checkpoint inhibitors for hepatocellular carcinoma patients with macrovascular invasion or extrahepatic spread: a systematic review and meta-analysis of 54 studies with 6187 hepatocellular carcinoma patients.

The impacts of macrovascular invasion (MVI) or extrahepatic spread (EHS) on the efficacy and safety of immune checkpoint inhibitors (ICIs) among hepatocellular carcinoma (HCC) patients remain unclear. Thus, we conducted a systematic review and meta-analysis to clarify whether ICI therapy is a feasible treatment option for HCC with MVI or EHS. Eligible studies published before September 14, 2022, were retrieved. In this meta-analysis, the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and occurrence of adverse events (AEs) were outcomes of interest. Fifty-four studies involving 6187 individuals were included. The findings indicated that the presence of EHS in ICI-treated HCC patients may indicate an inferior ORR (OR 0.77, 95% CI 0.63-0.96), but may not significantly affect the PFS (multivariate analyses: HR 1.27, 95% CI 0.70-2.31) and OS (multivariate analyses: HR 1.23, 95% CI 0.70-2.16). Additionally, the presence of MVI in ICI-treated HCC patients may not have significant prognostic impact on ORR (OR 0.84, 95% CI 0.64-1.10), but may indicate inferior PFS (multivariate analyses: HR 1.75, 95% CI 1.07-2.84) and OS (multivariate analyses: HR 2.03, 95% CI 1.31-3.14). The presence of EHS or MVI in ICI-treated HCC patients may not significantly impact the occurrence of any serious immune-related adverse events (irAEs) (grades ≥ 3) (EHS: OR 0.44, 95% CI 0.12-1.56; MVI: OR 0.68, 95% CI 0.24-1.88). The presence of MVI or EHS in ICI-treated HCC patients may not significantly impact the occurrence of serious irAEs. However, the presence of MVI (but not EHS) in ICI-treated HCC patients may be a significant negative prognostic factor. Therefore, ICI-treated HCC patients with MVI warrant more attention.

Is the sarcomatous component (homologous vs heterologous) the prognostic “driving force” in early-stage uterine carcinosarcomas? A retrospective multicenter study

PurposeUterine carcinosarcomas (UCSs) are aggressive biphasic malignancies, with a carcinomatous/epithelial component and a sarcomatous/mesenchymal counterpart. The aim of this study was to evaluate the impact of the sarcomatous component (homologous vs heterologous) on the overall survival (OS) and progression-free survival (PFS).MethodsThis is a multicenter observational retrospective study conducted in patients with stage I and II UCSs.ResultsNinety-five women with histological diagnosis of early-stage UCSs were retrieved: 60 (63.2%) had tumors with homologous sarcomatous components, and 35 (36.8%) with heterologous. At univariate analysis, a stromal invasion ≥ 50%, the presence of clear cell, serous or undifferentiated carcinomatous component, the heterologous sarcomatous component and FIGO stage IB and II were shown to be variables with a statistically significant negative impact on PFS. Similarly, a depth of invasion ≥ 50%, the heterologous sarcomatous component and FIGO stage IB and II were statistically negative prognostic factors also concerning OS. At multivariate analysis, only the heterologous sarcomatous component was confirmed to be a statistically significant negative prognostic factor both on PFS (HR 2.362, 95% CI 1.207–4.623, p value = 0.012) and on OS (HR 1.950, 95% CI 1.032–3.684, p = 0.040).ConclusionCarcinomatous and sarcomatous components both played a role in tumor progression and patients’ survival. However, only the sarcomatous component retained a statistical significance at the multivariable model suggesting its preeminent prognostic role in early-stage UCSs.

Prognostic values of the gross volume of metastatic lymph nodes in patients with esophageal squamous cell carcinoma treated with definitive concurrent chemoradiotherapy.

We aim to explore whether the gross volume of metastatic lymph nodes (GTVnd) and the gross volume of primary tumor (GTVp) could be prognostic factors for esophageal squamous cell carcinoma (ESCC) patients treated with definitive concurrent chemoradiotherapy (dCCRT). We retrospectively analyzed 252 ESCC patients treated with dCCRT in the eraofintensity-modulatedradiation therapy (IMRT) at our institution. The cut-off value for the GTVnd derived from the restricted cubic splines (RCS) was determined. Univariate and multivariate Cox proportional hazard models were performed to determine the association between GTVnd and prognosis. we performed recursive partitioning analysis (RPA) method using GTVnd to develop a new risk stratification (TGTVndM). Moreover, the linear trend χ2, likelihood ratio χ2, and akaike information criterion (AIC) were used to determine the prognostic value between the TNM and TGTVndM staging systems. The five-year overall survival (OS) rate was 30.6%, with a median follow-up of 38 months. The cut-off value of GTVnd determined by the RCS was 4.35 cm3. GTVnd≥4.35 cm3 was an independent and significant negative prognostic factor for OS (HR=1.949, P<0.001), progression free survival (PFS) (HR=1.425, P=0.048), and distance metastasis free survival (DMFS) (HR=2.548, P=0.001). In multivariable analysis, gender, clinical T stage, and GTVnd were independently associated with OS. RPA segregated patients into 3 prognostic groups: high risk (T1-4 GTVnd≥4.35, n=126, III stage), intermediate risk (T4 GTVnd<4.35,n=38,II stage), and low risk(T1-3GTVnd<4.35, n=88, I stage). The 5-year OS(P<0.001), PFS (P=0.002), and DMFS (P=0.001) were significantly worse in high-risk group in comparison with the intermediate and low risk groups. Compared with the TNM staging system, the clinical T stage combined with GTVnd (TGTVndM) had a higher linear trend χ2 (26.38 versus 25.77), higher likelihood ratio χ2 (24.39 versus 20.69), and lower AIC (1255.07 versus 1260.06). GTVnd may serve as a good prognostic factor in predicting distant metastasis and death for ESCC patients treated with dCCRT. The TGTVndM staging system demonstrated superior accuracy for predicting OS and could serve as a more effective prognostic guidance for unresectable ESCC patients.

Clinical Stage III NSCLC Patients Treated with Neoadjuvant Therapy and Surgery: The Prognostic Role of Nodal Characteristics.

The aim of this study is to analyze the prognostic factors in patients that underwent induction therapy and surgery for clinical stage III NSCLC. Clinical and pathological characteristics of stage III NSCLC patients for N2 involvement that underwent neoadjuvant treatment (NAD) and surgery from 1/01/1998 to 31/12/2017 were collected and retrospectively analyzed. Tumor characteristics, yClinical, yPathological stage and lymph node characteristics were correlated to Overall Survival (OS). The analysis was conducted on 180 patients. Five-year OS (5YOS) was 50.9%. Univariable analysis results revealed old age (p = 0.003), clinical N2 post-NAD (p = 0.01), pneumonectomy (0.005), persistent pathological N2 (p = 0.039, HR 1.9, 95% CI 1.09-2.68) and adjuvant therapy absence (p = 0.049) as significant negative prognostic factors. Multivariable analysis confirmed pN0N1 (p = 0.02, HR 0.29, 95% CI 0.13-0.62) as a favorable independent prognostic factor and adjuvant therapy absence (p = 0.012, HR 2.61, 95% CI 1.23-5.50) as a negative prognostic factor. Patients with persistent N2 presented a 5YOS of 35.3% vs. 55.8% in pN0N1 patients. Regarding lymph node parameters, the lymph node ratio (NR) significantly correlated with OS: 5YOS of 67.6% in patients with NR &lt; 50% vs. 29.5% in NR &gt; 50% (p = 0.029). Clinical response aided the stratification of prognosis in patients that underwent multimodal treatment for stage III NSCLC. Adjuvant therapy seemed to be an important option in these patients, while node ratio was a strong prognosticator in patients with persistent nodal involvement.

Influence of confirmed viral infection on adult acute fulminant myocarditis supported with extracorporeal membrane oxygenation.

The impact of etiologies of acute fulminant myocarditis (AFM), which requires extracorporeal membrane oxygenation (ECMO), on clinical outcomes remains unknown. This study aimed to investigate the risk factors for ECMO weaning and mortality among patients with AFM due to viral etiologies in a tertiary referral medical center. We included 33 adults with AFM who received ECMO and were admitted between January 2002 and January 2021. General demographics, laboratory data, echocardiography findings, and long-term outcomes were analyzed for confirmed viral etiology and unconfirmed etiology groups. The overall hospital survival rate was 54.5%. The age, sex, severity of the hemodynamic condition, and cardiac rhythm were similar between the two groups. Multivariate Cox regression analysis revealed that a confirmed viral etiology (HR 4.201, 95% CI 1.061-16.666), peri-ECMO renal replacement therapy (RRT) (HR 9.804, 1.140-83.333) and a high positive end-expiratory pressure (PEEP) in the ventilator settings at 24 h after ECMO (HR 1.479, 1.020-2.143) were significant prognostic factors for in-hospital mortality. Peri-ECMO RRT was also a significant negative prognostic factor for successful ECMO weaning (OR 0.061, 0.006-0.600) in the multivariate logistic model. Among AFM patients receiving ECMO support, RRT use was associated with a decreased chance of survival to ECMO weaning. Multiple organ dysfunction and a high PEEP were also predictive of a lower chance of hospital survival. Those with a confirmed diagnosis of viral myocarditis may require more medical attention due to the higher risk of hospital mortality than those without a definite diagnosis.

Impact of myometrium invasion on survival outcomes following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC).

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is an effective surgical intervention for peritoneal surface malignancy. The effect of myometrium invasion on outcomes is unknown. Retrospective review of our institutional registry with analysis of CRS-HIPEC cases involving a hysterectomy. Compared cases with myometrium invasion versus those without invasion. Primary outcome was survival as measured by overall survival (OS) and disease-free survival (DFS). Secondary outcome was the evaluation of risk factors for myometrium invasion based on multivariate analysis. A total of 126 cases of CRS-HIPEC involving a hysterectomy were identified. Ninety-seven cases (76.9%) had no myometrium invasion and the remaining 29 cases (23.1%) had malignant invasion. The presence of myometrial invasion was a significant negative survival prognostic factor. The OS was halved with mean survival times of 2.8 (±2.3) versus 5.8 (±4.7) years for cases with and without invasion, respectively (p = 0.002). Five-year OS rates were also inferior with myometrium invasion at 17.4% versus 53.8% (odds ratio [OR] = 0.181, 95% confidence interval [CI]: 0.057-0.580, p = 0.002). A similar trend was present with DFS with mean survival times of 1.4 (±0.9) versus 3.7 (±3.9) years for noninvasion and invasion cases (p = 0.009). The 5-year DFS rates were 0% versus 34.8% (OR = 0.652, 95% CI: 0.549-0.775, p = 0.004). Secondary analysis significantly associated several risk factors with myometrium invasion to include lymph node positivity (OR = 2.539, 95% CI: 1.074-6.003, p = 0.012), colorectal primary tumors (OR = 2.248, 95% CI: 1.094-5.161, p = 0.035), and high-grade tumors (OR = 2.160, 95% CI: 1.080-4.820, p = 0.038). Myometrium invasion is a significant negative prognostic factor for survival following CRS-HIPEC. Several risk factors are potentially predictive of identifying those at high-risk for myometrium invasion.

The prognostic value of positron emission tomography/computed tomography-based parameters in locally advanced esophageal squamous cell carcinoma treated with chemoradiation therapy.

To assess the prognostic value of PET/computed tomography-based parameters in patients with locally advanced esophageal squamous cell carcinoma (ESSC). Sixty-seven patients with ESSC undergoing definitive chemoradiotherapy (dCRT) were retrospectively enrolled. PET/CT parameters (maximum standardized uptake value (SUVmax) metabolic tumor volume (MTV), and total glycolysis (TLG) were obtained from 18F-fluorodeoxyglucose (18F-FDG) PET/CT studies. The correlation between overall survival and PET/CT parameters was analyzed using a Cox proportional hazards model. There were no differences in TLG, MTV, and SUVmax values across age, sex, tumor location, and lymph node status. However, for patients with cT3-4 disease, TLG and SUVmax were significantly higher (P = 0.019 and P = 0.018, respectively), and MTV showed an increasing trend (P = 0.068). There were significant correlations among TLG, MTV and SUVmax. According to the receiver-operating curve, the cutoff values of TLG, MTV and SUVmax dichotomized by survival status at 2 years were 64.00 g, 9.63 ml and 9.97 g/ml, respectively. In univariate analysis, increased TLG, MTV and SUVmax were significant negative prognostic factors for OS. However, in multivariate analysis, only SUVmax was an independent prognostic factor for overall survival (hazard ratios = 2.857, 95% confidence intervals: 1.837-4.442; P = 0.017). PET/CT is a useful tool for predicting the prognoses in patients with locally advanced ESSC treated with dCRT. Future prospective studies with a large number of samples should be conducted to confirm these results.

COVID-19 in sub-intensive care unit: An italian single-center experience along the three epidemic waves

The goal was to characterize COVID-19 patients who needed treatment in Sub-Intensive Care Units (SICUs) for hypoxemic respiratory failure, describe their six-month mortality, and identify clinical and laboratory characteristics that were associated with death. Data from 216 consecutive patients admitted to the COVIDSICU of Turin’s San Giovanni Bosco Hospital were analyzed retrospectively. A total of 216 patients (24.5% of whom were female) were enrolled. The average age was 63±11.9 years. In the three waves, the six-month mortality rate was 32.8%, 35.1%, and 26.6%, respectively (p=0.52). The mortality rate was significantly higher in intubated patients compared to those not requiring intubation (60.8% versus 29.9%, p&lt;0.01). On admission, deceased patients were older (69±7.7 versus 60.2±12.6 y.o., p&lt;0.01), with a higher prevalence of dyslipidemia, coronary artery disease, chronic heart failure, and higher serum creatinine. However, only age was predictive of death at multivariate analysis (OR 5.29, p&lt;0.01), with 63 years old as the best cut-point. At six months, mortality in COVID patients managed in a SICU is around 30%. Age is a significant negative prognostic factor, with 63 years of age being the best predicting cut-off.

Intrahepatic cholangiocarcinoma: risk factors affecting survival of operated patients.

The aim of this study was to evaluate the results of surgical treatment of intrahepatic cholangiocarcinoma (IHCHCA) in terms of overall survival and disease-free survival, and to analyse and find potential prognostic factors affecting overall survival and disease-free survival. Retrospective evaluation was performed of consecutively enrolled patients operated for IHCHCA from January 2005 to January 2022 (17 years) had undergone surgery. During the monitored period, 38 surgical procedures were performed, of which liver resection was done in 25 cases (65.8%). The 5-year survival in the radically resected group was 44%, and the 5-year disease-free survival was 32%. Based on univariate and multivariate analysis, radicality of surgery (p=0.01116) and lymph node involvement (p=0.00576) were assessed as negative prognostic factors for overall survival. Radicality of surgery (p=0.018) and administration of adjuvant chemotherapy (p=0.044) were significant negative prognostic factors affecting disease-free survival. However, they lost their significance in the multivariate analysis. Radical surgical resection of the liver remains an essential treatment option for intrahepatic cholangiocarcinoma aimed at achieving a radical procedure with microscopically negative margins. cholangiocarcinoma, resection, recurrence, survival.