Negative Predictor Of Survival Research Articles

A comparison of endoscopic endonasal versus open approaches for skull base chordoma: a comprehensive National Cancer Database analysis.

The authors of this study aimed to investigate independent prognostic factors of survival with a particular focus on comparing the safety and efficacy of endoscopic endonasal versus open approaches in the surgical management of skull base chordoma. A retrospective National Cancer Database review of skull base chordoma patients was performed to capture resection cases from 2010 to 2020, evaluating overall survival (OS), early postoperative mortality, readmission rates, and hospital length of stay (LOS) between surgical approaches and the independent prognostication of death utilizing Cox multivariate regression analysis. Among the 736 patients included in the cohort, 456 patients (62.0%) and 280 patients (38.0%) underwent endoscopic endonasal and open resection, respectively. These values represent a rate of change over the study period of +4.1 versus -0.14 cases per year, respectively. Gross-total resection was achieved in 32.5% of cases. A positive margin status was found in 51.8% of cases. There was no association between extent of resection and surgical approach (p = 0.257). There was no difference in OS (p = 0.562), 30- and 90-day mortality (p = 0.209 and 0.126, respectively), and 30-day readmission (p = 0.438) between the two surgical groups. The mean LOS was reduced by 2.1 days in the endoscopic cohort (p = 0.013) compared with the open approach cohort. Finally, multivariate analysis revealed a tumor size ≥ 4 cm (HR 4.03, p = 0.005) and public insurance (HR 2.76, p = 0.004) as negative predictors of survival and treatment at an academic center (HR 0.36, p = 0.043) as a positive prognosticator of survival. The endoscopic endonasal approach has been increasingly utilized over time and touts noninferiority with respect to safety and efficacy with a marked improvement in LOS, which carries substantial implications for both healthcare costs and enhanced patient recovery. Future prospective studies are necessary to further delineate trends and surgical outcomes for skull base chordoma.

Lymph node examination and survival in resected pancreatic ductal adenocarcinoma: retrospective study.

The minimum number of examined lymph nodes (ELN) required for adequate staging and best prediction of survival has not been established in pancreatic ductal adenocarcinoma (PDAC). The aim of the study was to investigate the influence of ELN on staging and survival in PDAC. Patients undergoing partial or total pancreatectomy for PDAC at two European university hospitals between 2007 and 2018 were retrospectively reviewed. Multivariate Cox regression model and survival analyses were performed to verify adequate staging. Overall 341 (73 per cent) patients showed lymph node metastasis (N1/N2), whereas 125 (27 per cent) patients had no lymph node involvement (N0). With increasing number of ELN, the proportion of positive lymph nodes increased. The minimum number of ELN needed to detect lymph node involvement was 21. In multivariate analysis, examination of <21 lymph nodes was a significant negative predictor for survival. Examination of ≥21 ELN reversed this effect and ruled out possible misclassification. The number of ELN affects survival in PDAC. Possible misclassification was identified when <21 lymph nodes were examined. Therefore, at least 21 lymph nodes must be examined to avoid false lymph node classification in all types of resection.

PATH-35. SHIFTS IN GLIOMA PROGNOSTIC MOLECULAR FEATURES ACROSS THE LIFESPAN

Abstract INTRODUCTION Epidemiological studies examining glioma prognostic features have consistently identified older age as a negative predictor of survival. Accumulation and co-occurrence of favorable or deleterious molecular alterations across the lifespan likely plays a role in the age-dependent variability seen in glioma patient outcomes. METHODS We assembled 4,297 molecularly and clinically annotated glioma patients from multi-institutional datasets and TCGA, with IDH1/2-mutation, MGMT-methylation, and chromosome 1p19q codeletion status assayed. Patient age was stratified: pediatric (&amp;lt; 20 years), young adult (20-39 years), middle aged (40-64 years), and older adults ( &amp;gt;65 years). Pairwise proportions were tested to study distribution of alterations across age as well as variability in assaying for MGMT-methylation. RESULTS 4,297 patients with glioma were identified with molecular annotation of IDH1/2-mutation status (40.1% IDH1/2-mutant). Of assayed gliomas, 44.3% were MGMT-methylated and 13.9% had chromosome 1p19q codeletion. IDH1/2-mutation incidence decreased with age across all gliomas (85% in young adults, 35% middle aged, and 8% older adults) and in grade 4 gliomas (64% IDH1/2-mutation in young adults, 9% middle aged, and 2% older adults). 1p19q codeletion also decreased in incidence with increasing age (young adult 22%, middle aged 15%, older adults 6%). MGMT-methylation remained consistent across adult patients, between 43-50% across all gliomas. Interestingly, amongst the few patients &amp;gt;65 years old with IDH1/2-mutation or 1p19q codeletion, 87% possessed co-occurring MGMT-methylation, significantly greater than young adults (54%, p&amp;lt; 0.001). Consistent with this, 82% of patients &amp;gt;65yrs with grade 4 IDH1/2-mutant gliomas had co-occurring MGMT-methylation. Despite the treatment response implication of MGMT-methylation, 72.2% of low-grade gliomas were not assayed for MGMT. CONCLUSIONS There is an age-dependent pattern of molecular alterations in gliomas, with the incidence of certain favorable prognostic signatures decreasing over time. Given the stability of MGMT-methylation across the age spectrum and grade, more widespread MGMT profiling may be beneficial to guide treatment decisions.

Molecular Markers Are Associated with Onset of Radioiodine Refractoriness in Patients with Papillary Thyroid Carcinoma.

The onset of radioiodine-refractory thyroid carcinoma (RR-TC) is a negative predictor of survival and has been linked to the presence of BRAFV600E mutations in papillary thyroid cancer. We aimed to identify further genetic alterations associated with RR-TC. Methods: We included 38 patients with papillary thyroid cancer who underwent radioiodine imaging and 18F-FDG PET/CT after total thyroidectomy. The molecular profile was assessed by next-generation sequencing. The time to the onset of RR-TC for different genetic alterations was compared using the log-rank test. Results: The median onset to RR-TC was 0.7 and 19.8 mo in patients with and without, respectively, telomerase reverse transcriptase promoter mutations (P = 0.02) and 1.7 and 19.8 mo in patients with and without, respectively, a tumor protein 53 mutation (P < 0.01). This association was not observed for BRAFV600E mutations (P = 0.49). Conclusion: Our data show a significant association between the onset of RR-TC and mutations in telomerase reverse transcriptase promoter and tumor protein 53, indicating the need for a more extensive diagnostic workup in these patients. Certain genetic changes put patients with thyroid cancer at risk of developing cancer spread that does not respond to radioiodine therapy.

Predictors of outcomes in hematopoietic cell transplantation for Fanconi anemia

Allogeneic hematopoietic cell transplantation (HCT) remains the only cure for the hematologic manifestations of Fanconi anemia (FA). We performed retrospective predictor analyses for HCT outcomes in FA for pediatric and young adult patients transplanted between 2007 and 2020 across three large referral institutions. Eighty-nine patients, 70 with bone marrow failure +/− cytogenetic abnormalities, 19 with MDS/AML, were included. Five-year overall survival (OS) was 83.2% and event-free survival (EFS) was 74%. Age ≥19, HLA mismatch and year of HCT were multivariable predictors (MVPs) for OS, EFS and treatment-related mortality (TRM). In the pediatric group, TCD was a borderline MVP (P = 0.059) with 5-year OS of 73.0% in TCD vs. 100% for T-replete HCT. The cumulative incidence of day 100 grade II-IV aGvHD and 5-year cGvHD were 5.6% and 4.6%, respectively. Relapse in the MDS/AML subgroup occurred in 4 patients (16%). Graft failure was seen in 9 patients (TCD 6/37 [16%]; T-replete 3/52 [5.7%]). Six patients developed malignancy after HCT. Survival chances after HCT for FA are excellent and associated with high engrafted survival and low toxicity. Age ≥19, HLA mismatch, year of transplant and ‘TCD in the <19 years group’ (although borderline) were found to be negative predictors for survival.

Immune Cell Deconvolution Reveals Possible Association of γδ T Cells with Poor Survival in Head and Neck Squamous Cell Carcinoma.

(1) Background: The role of rare immune cell subtypes in many solid tumors, chief among them head and neck squamous cell carcinoma (HNSCC), has not been well defined. The objective of this study was to assess the association between proportions of common and rare immune cell subtypes and survival outcomes in HNSCC. (2) Methods: In this cohort study, we utilized a deconvolution approach based on the CIBERSORT algorithm and the LM22 signature matrix to infer proportions of immune cell subtypes from 517 patients with untreated HPV-negative HNSCC from The Cancer Genome Atlas. We performed univariate and multivariable survival analysis, integrating immune cell proportions with clinical, pathologic, and genomic data. (3) Results: We reliably deconvolved 22 immune cell subtypes in most patients and found that the most common immune cell types were M0 macrophages, M2 macrophages, and memory resting CD4 T cells. In the multivariable analysis, we identified advanced N stage and the presence of γδ T cells as independently predictive of poorer survival. (4) Conclusions: We uncovered that γδ T cells in the tumor microenvironment were a negative predictor of survival among patients with untreated HNSCC. Our findings underscore the need to better understand the role of γδ T cells in HNSCC, including potential pro-tumorigenic mechanisms, and whether their presence may predict the need for alternative therapy approaches.

THU518 Ectopic Cushing Syndrome In A Case Of Ewing Sarcoma

Abstract Disclosure: M. Fasen: None. S.E. Mayson: None. Background: Ewing sarcoma (ES) is a rare and aggressive neoplasm occurring in bone and soft tissue in children to young adults. It is part of a spectrum of neoplastic diseases known as the ES family of tumors that display varying degrees of neuroendocrine features. Ectopic Cushing’s syndrome (ECS) is also a rare but severe condition associated with unregulated ACTH or CRH secretion by neuroendocrine tumors (NETs) that can cause severe hypercortisolism. The most common tumors associated with ECS include small cell lung carcinoma, bronchial carcinoid and medullary carcinoma of the thyroid gland. Sarcomas causing ECS are extremely rare with only a handful of cases reported in the literature, mostly in children. Herein we detail what we believe to be the first reported case of ECS occurring in an adult male patient with ES. Clinical Case: A 23-year-old man with ES metastatic to pancreas, liver and bone was admitted to the hospital with acute on chronic back pain and lower extremity weakness, and subsequently diagnosed with cord compression and neutropenia from chemotherapy. New onset hypertension and refractory hypokalemia were observed prompting endocrinology consultation. Physical examination revealed facial fullness, central obesity and wide violaceous striae on his abdomen and axillae. Biochemical evaluation demonstrated blood glucose consistently over 300 mg/dL, serum potassium 2.5 mmol/L, renin 0.9 ng/ml/hr (0.2-1.6 ng/ml/hr), aldosterone renin ratio &amp;lt; 3.3, morning cortisol 73 ug/dL (4-22 ug/dL), and ACTH 1020 pg/mL (72-63 pg/mL). A 1 mg overnight dexamethasone suppression test yielded a serum cortisol of 90 ug/dL and 24-hour urine free cortisol was 6388 ug/d (&amp;lt;60 ug/d). MRI brain demonstrated a normal pituitary gland, and FDG PET-CT showed new areas of uptake in bone concerning for metastatic progression and new bilateral adrenal enlargement without nodularity. High dose dexamethasone suppression testing was deferred in the context of rapid neuropsychiatric deterioration characterized by somnolence and psychosis. The decision was made to treat immediately with spironolactone and ketoconazole, as well as insulin for hyperglycemia management. His mental status, blood pressure, serum potassium, glucose and cortisol improved following the initiation and titration of medical therapy. He was discharged home with addition of metyrapone and hospice support. Two months later the patient succumbed to his illness. Conclusion: The severity of hypercortisolism is a negative predictor of survival and prompt control should be the main therapeutic goal along with prevention of cortisol-induced complications in patients with ECS. ACTH and CRH immunostaining of the patient’s ES histopathology slides is pending. Presentation: Thursday, June 15, 2023

Cardiomyopathy as cause of death in Duchenne muscular dystrophy: a longitudinal observational study.

Cardiomyopathy has become an important life-limiting factor since survival in Duchenne muscular dystrophy (DMD) has greatly increased with long-term ventilation and cough assistance. The aim of this study was to investigate the association between impaired left ventricular ejection fraction (LVEF) and survival. In a >20-year observational study in patients with DMD (age ≥16 years) with at least three echocardiograms, the association between LVEF and survival and time to cardiac or non-cardiac death was investigated using Kaplan-Meier survival analysis and Cox regression (for LVEF). In 67 DMD patients (430 echocardiograms), the decrease in LVEF over a mean±sd follow-up period of 9.1±5.1 years was -10.0±13.9% absolute, but LVEF progression varied widely. 84% were receiving an angiotensin-converting enzyme inhibitor and 54% a β-blocker at last follow-up with an LVEF of 37.5±12.4% at that time-point. Median (interquartile range) survival was 33 (25-40) years. 28 out of 67 (42%) of the cohort had died and LVEF was a significant negative predictor of survival (hazard ratio 0.95 (95% CI 0.91-0.99); p<0.007). Those who died of cardiac death (53% of known causes of death) had significantly lower LVEF at the time of death (LVEF -11.0% (95% CI -21.1- -0.9%); p=0.035) compared with non-cardiac death and tended to die at a younger age. Cardiomyopathy with systolic heart failure is the leading cause of death and lower LVEF is an independent predictor of mortality at younger ages in patients with DMD. Patients with DMD appear to be undertreated with respect to heart failure drug therapy.

Impact of a targeted temperature management quality improvement project on survival and neurologic outcomes in cardiac arrest patients.

Targeted temperature management (TTM) is recommended for postresuscitation care of patients with sudden cardiac arrest (SCA) and its implementation remains challenging. This study aimed to evaluate the newly designed Quality Improvement Project (QIP) to improve the quality of TTM and outcomes of patients with SCA. Patients who experienced out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA) with return of spontaneous circulation (ROSC) and were treated in our hospital between January 2017 and December 2019 were enrolled retrospectively. All included patients received QIP intervention initiated as follows: (1) Protocols and standard operating procedures were created for TTM; (2) shared decision-making was documented; (3) job training instruction was created; and 4) lean medical management was implemented. Among 248 included patients, the postintervention group (n = 104) had shorter duration of ROSC to TTM than the preintervention group (n = 144) (356 vs 540 minutes, p = 0.042); better survival rate (39.4% vs 27.1%, p = 0.04), and neurologic performance (25.0% vs 17.4%, p < 0.001). After propensity score matching (PSM), patients who received TTM (n = 48 ) had better neurologic performance than those without TTM (n = 48) (25.1% vs 18.8%, p < 0.001). OHCA (odds ratio [OR] = 2.705, 95% CI: 1.657-4.416), age >60 (OR = 2.154, 95% CI: 1.428-3.244), female (OR = 1.404, 95% CI: 1.005-1.962), and diabetes mellitus (OR = 1.429, 95% CI: 1.019-2.005) were negative predictors of survival; while TTM (OR = 0.431, 95% CI: 0.266-0.699) and bystander cardiopulmonary resuscitation (CPR) (OR=0.589, 95% CI: 0.35-0.99) were positive predictors. Age >60 (OR= 2.292, 95% CI: 1.58-3.323) and OHCA (OR= 2.928, 95% CI: 1.858-4.616) were negative predictors of favorable neurologic outcomes; while bystander CPR (OR=0.572, 95% CI: 0.355-0.922) and TTM (OR=0.457, 95% CI: 0.296-0.705) were positive predictors. A new QIP with defined protocols, documented shared decision-making, and medical management guidelines improves TTM execution, duration from ROSC to TTM , survival, and neurologic outcomes of cardiac arrest patients.

Radial and longitudinal margins in surgery of perihilar cholangiocarcinoma: When R1 definition is associated with different prognosis

BackgroundInfiltrated margins of resection (R1) and lymph node invasion are dominant negative predictors of survival in patients with a resectable perihilar cholangiocarcinoma. Less clear is whether survival predictors stratify differently between R0 (tumor-free margins) and R1 patients and whether the prognosis of the latter patients is influenced by the pattern of neoplastic infiltration (ie, radial versus longitudinal infiltration). We retrospectively evaluated a series of reported resected perihilar cholangiocarcinoma to obtain insights on the predictive power of these histologic features. MethodsThe study includes 264 patients with perihilar cholangiocarcinoma treated between 2004 and 2019 in our center and followed up for >18 months. There were 176 patients with R0 (66.6%) and 88 patients with R1 (33.3%), 31 with radial infiltration only, 30 with longitudinal infiltration only, and 27 with both infiltration patterns. In all patients, the criteria for resection was the absence of metastatic involvement (ie, distant organ metastases, liver metastases, and lymph node metastases beyond the hepatoduodenal ligament). Histopathologic specimens of the resected tumors were centrally reviewed by a pathologist unaware of the clinical outcomes. ResultsThree- and 5-year long-term survival were significantly better in R0 (respectively) compared to R1 patients (55% and 42% vs 42% and 18%, respectively, P < .05). In R1 patients with radial infiltration only and those with radial + longitudinal infiltration, both disease-free and overall survival were worse than those with longitudinal infiltration only (median disease-free survival of 18 and 23 months, respectively, P < .05, median overall survival of 33 and 39 months, respectively, P < .05). At multivariable analysis, nodal status, side of hepatectomy, grading, and presence of radial margin infiltration were associated with long-term outcome. ConclusionRadial infiltration of resection margins enhances the negative prognostic value of R1 margins in perihilar cholangiocarcinoma patients and should specifically be accounted for in the prediction of the outcome of adjuvant therapy.

Pancreatic Diffuse Large B-cell Lymphoma in the US Population.

Pancreatic lymphomas (PLs) represent <2% of all lymphomas and <0.5% of all pancreatic neoplasms. An accurate histologic diagnosis of PL is needed to predict prognosis and adequately treat the patient. This study aims to investigate the demographic, clinical, and pathological factors affecting the prognosis and survival of pancreatic diffuse large B-cell lymphoma (DLBCL). Demographic and clinical data from 493 cases of DLBCL of the pancreas were identified between 2000 and 2018 using the Surveillance, Epidemiology, and End Results (SEER) database. The most common age group was between the ages of 70 and 79 years (27.0%).While 44%of cases involved distant sites (a proxy for secondary pancreatic DLBCL), regional and localized involvement was seen in 33%, with the most common cause of death being a primary pancreatic DLBCL. Most patients (71%) received only chemotherapy (systemic therapy). The overall five-year observed survival was 46% (95% CI, 43.5-48.3). The one-year and five-year survival with chemotherapy only was 68% (95% CI, 65.3-70.3) and 48% (95% CI, 44.7-50.5), respectively. The one-year and five-year survival with surgery and chemotherapy was 96% (95% CI, 91.3-99.9) and 80% (95% CI, 71.4-89.2), respectively. Surgery with chemotherapy (HR: 0.397 (95% CI, 0.197-0.803), p = 0.010) were both positive predictors in survival prognosis. Multivariable analysis identified age >55 years (HR: 2.475 (95% CI, 1.770-3.461), p < 0.001), distant stage (HR: 6.894 (95% CI, 4.121-11.535), p < 0.001), and undergoing no surgery (HR: 2.610 (95% CI, 1.307-5.215), p = 0.007) as negative predictors for survival. PLs are rare malignant pancreatic neoplasms with DLBCL being the most common histological subtype. An accurate and timely diagnosis of pancreatic DLBCL is necessary to implement effective treatments and reduce mortality. Systemic therapy (chemotherapy) with or without surgical therapy improved survival. Increased age and regional and distant spread negatively impacted survival.

Post-transplant Lymphoproliferative Disorder (PTLD) in the US Population: Demographics, Treatment Characteristics, and Survival Analysis.

Post-transplant lymphoproliferative disorder (PTLD) is a lymphoplasmacytic proliferative disorder in the setting of hematopoietic stem cells and solid organ transplants. PTLD is divided into nondestructive, polymorphic, monomorphic, and classical Hodgkin lymphoma subtypes. Most cases of PTLDs are Epstein-Barr virus (EBV) related (two third of the cases), and most are of B cell (80-85%) origin. The polymorphic PTLD subtype can be locally destructive and show malignant features. Treatment for PTLD includes a reduction in immunosuppression, surgery, cytotoxic chemotherapy and/or immunotherapy, anti-viral agents, and/or radiation. The aim of this study was to examine the demographic factors and treatment modalities that influence survival in patients with polymorphic PTLD. About 332 cases of polymorphic PTLD were identified from 2000 to 2018 using the Surveillance, Epidemiology, and End Results (SEER) database. The median age of the patients was found to be 44 years. The most common age groups were between the ages of 1-19 years (n=100. 30.1%) and 60-69 years (n=70. 21.1%). The majority of cases in this cohort underwent systemic (cytotoxic chemo and/or immuno) therapy only (n=137, 41.3%), while 129 (38.9%) cases did not undergo any treatment. The overall five-year observed survival was 54.6% (95% confidence interval (CI), 51.1 - 58.1). One-year and five-year survival with systemic therapywas 63.8% (95% CI, 59.6 - 68.0) and 52.5% (95% CI, 47.7 - 57.3), respectively. The one-year and five-year survival with surgerywas 87.3% (95% CI, 81.2-93.4) and 60.8% (95% CI., 42.2 - 79.4), respectively. The one-year and five-year without therapy were 67.6% (95% CI, 63.2-72.0) and 49.6% (95% CI, 43.5-55.7), respectively. Univariate analysis revealed thatsurgery alone (hazard ratio (HR) 0.386 (0.170-0.879), p = 0.023) was a positive predictor of survival. Race and sex were not predictors of survival, although age >55 years was a negative predictor for survival (HR 1.128 (1.139-1.346), p <0.001). Polymorphic PTLD is a destructive complication of organ transplantation that is usually associated with EBV positivity. We found that it most often presents in the pediatric age group, and its occurrence in those older than 55 years was associated with a worse prognosis. Treatment with surgery alone is associated with improved outcomes and should be considered in addition to a reduction in immunosuppression in cases of polymorphic PTLD.

Chronic Obstructive Pulmonary Disease and Its Effect on Red Blood Cell Indices.

Chronic obstructive pulmonary disease (COPD) constitutes a set of heterogeneous symptoms affecting millions of people worldwide. The associated comorbidities developing in COPD involve dysregulation in physiological pathways resulting from systemic inflammation in respiratory airways. In addition to mentioning the pathophysiology, stages, and consequences of COPD, this paper also defines red blood cell (RBC) indices such as hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin concentration, red blood cell distribution width, and RBC count. It explains the role of RBC indices and RBC structural abnormalities with disease severity and exacerbations in COPD patients. Although many factors have been studied as a marker of morbidity and mortality for COPD patients, RBC indices have emerged as revolutionary evidence. Therefore, the effectiveness of evaluating RBC indices in COPD patients and their importance as a negative predictor of survival, mortality, and clinical outcomeshave been debated through rigorous literature reviews. Furthermore, the prevalence, mechanisms of development, and prognosis of underlying anemia and polycythemia in COPD have also been evaluated, with anemia most significantly associated with COPD. Therefore, more studies should be conducted to address underlying anemia in COPD patients to lessen the severity and disease burden. Correcting the RBC indices in COPD patients remarkably impacts the quality of life and reduces in-patient admissions, healthcare resource utilization, and costs. Hence, it is noteworthy to understand the significance of considering RBC indices while dealing with COPD patients.

Age, sex, primary tumor type and site are associated with mortality after pathological fractures: an observational study of 1453 patients from the Swedish Fracture Register

BackgroundPathological fractures are challenging in orthopedic surgery and oncology, with implications for the patient’s quality of life, mobility and mortality. The efficacy of oncological treatment on life expectancy for cancer patients has improved, but the metastatic pattern for bone metastases and survival is diverse for different tumor types. This study aimed to evaluate survival in relation to age, sex, primary tumor and site of the pathological fractures.MethodsAll pathological fractures due to cancer between 1 September 2014 and 31 December 2021 were included in this observational study from the Swedish Fracture Register (SFR). Data on age, sex, tumor type, fracture site and mortality were collected.ResultsA total of 1453 patients with pathological fractures were included (48% women, median age 73, range 18–100 years). Unknown primary tumors were the most common primary site (n = 308). The lower extremities were the most common site of pathological fractures. Lung cancer had the shortest median survival of 78 days (range 54–102), and multiple myeloma had the longest median survival of 432 days (range 232–629). The site at the lower extremity had the shortest (187 days, range 162–212), and the spine had the longest survival (386 days, range 211–561). Age, sex, primary type and site of the pathological fractures were all associated with mortality.InterpretationAge, sex, primary tumor type and site of pathological fractures were associated with survival. Survival time is short and correlated with primary tumor type, with lung cancer as the strongest negative predictor of survival.

Role of IL4 and GMCSF in Predicting Survival in Esophageal Cancer.

Esophageal cancer (EC) originates in the setting of chronic inflammation. Although previous studies have sought to understand the role of inflammatory signaling in EC, the effect of these immunologic changes on patient outcomes remains understudied. This study's objective was to identify relationships between cytokine levels and prognosis in a mixed cohort of esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) patients. A total of 37 serum cytokines were profiled at the time of resection using multiplex ELISA in 47 patients (42 esophageal adenocarcinoma, 5 esophageal squamous cell carcinoma). Cytokine levels were median-binarized and assessed using Cox regression models. Findings were validated at the RNA level using The Cancer Genome Atlas EC cohort (81 esophageal adenocarcinoma, 81 esophageal squamous cell carcinoma). Univariable analysis revealed high serum interleukin 4 (IL4) and granulocyte-macrophage colony-stimulating factor (GMCSF) were negatively associated with overall survival (p = 0.046, p = 0.040). Multivariable analysis determined both high serum IL4 or high serum GMCSF were negatively associated with survival independent of important clinical factors (hazard ratio [HR] 7.55, p < 0.001; HR 5.24, p = 0.001). These findings were validated at the RNA level in The Cancer Genome Atlas EC cohort, where multivariable analysis identified high IL4 expression, high CSF2 expression (encodes GMCSF), and advanced pathologic stage as independent negative predictors of survival when controlled for clinical factors (HR 2.35, p = 0.012; HR 1.97, p = 0.040). These results show that high IL4/GMCSF levels are negatively associated with survival in EC. These relationships are independent of pathologic stage and are identified across modalities, histologic subtypes, and the presence/absence of neoadjuvant therapy.

The prognostic value of sarcopenia in oesophageal cancer: A systematic review and meta-analysis.

The loss of skeletal muscle mass and function is defined as sarcopenia, which might develop in elderly patients with cancers. It has been indicated as a potential negative factor in the survival of patients with malignant tumours. The aim of this systematic review and meta-analysis was to evaluate the associations between sarcopenia and survival outcomes or postoperative complications in patients with oesophageal cancer (EC). Web of Science, Embase, Medline, and Cochrane Library databases were searched until 10 May 2022, using keywords: sarcopenia, oesophageal cancer, and prognosis. Studies investigating the prognostic value of sarcopenia on EC survival were included. Forest plots and summary effect models were used to show the result of this meta-analysis. The quality of included studies was evaluated with the Newcastle-Ottawa Scale (NOS). A total of 1436 studies were identified from the initial search of four databases, and 41 studies were included for the final quantitative analysis. This meta-analysis revealed a significant association between sarcopenia and overall survival (OS) [hazard ratios (HR):1.68, 95% confidence interval (CI):1.54-1.83, P=0.004, I2 =41.7%] or disease-free survival (DFS) 1.97 (HR: 1.97, 95% CI: 1.44-2.69, P=0.007, I2 =61.9%) of EC patients. Subgroup analysis showed that sarcopenia remained a consistent negative predictor of survival when stratified by different treatment methods, populations, or sarcopenia measurements. Sarcopenia was also a risk factor for postoperative complications with a pooled odds ratio of 1.47 (95% CI: 1.21-1.77, P=0.094, I2 =32.7%). The NOS scores of all included studies were ≥6, and the quality of the evidence was relatively high. The results from the study suggested that sarcopenia was significantly associated with both survival outcomes and postoperative complications in EC patients. Sarcopenia should be appropriately diagnosed and treated for improving short-term and long-term outcomes of patients with EC.

456. THE PROGNOSTIC IMPACT OF TUMOR BUDDING IN ESOPHAGEAL ADENOCARCINOMA

Abstract In a previous study on esophageal adenocarcinoma (EAC) cases submitted to surgery (without neoadjuvant treatment), an algorithm (EACGSE classification) 1 based on morphologic distinctions provided significant prognostic impact. Tumor budding is a specific type of invasive growth pattern and was found to be an important prognostic parameter in gastrointestinal cancers. 2–3 We aimed to evaluate the prevalence of budding in glandular adenocarcinomas and its impact on survival. The EAC cohort classified according to EACGSE 1 was included in the study: among the different histotypes, 215 cases, classified as well (WD) and poorly (PD) differentiated glandular adenocarcinomas, were considered. Tumor budding was defined as single cells or clusters of up to four cells at the invasive margin. Budding was grouped according to ITBCC 2 into Bd1 (0-4 buds), Bd2 (5-9 buds), and Bd3 (10 or more buds). Furthermore, the most prognostically relevant cut off for bud number in EAC was defined by ROC analysis. Cancer specific survival analyses were performed using the Kaplan–Meier method and Cox regression analyses. Tumor budding was assessed in one hotspot (a field measuring 0.785 mm2) at the invasive front and ROC analysis identified 8 buds per field cut off as the most informative in relation to survival. By using this cut off, frequency of budding was higher in glandular PD (84/124,68%) cases than in WD ones (7/91,8%, p &amp;lt; 0.001). Budding was a strong negative predictor of survival both in univariate (p &amp;lt; 0.001) and multivariate analyses (p &amp;lt; 0.001) (Fig. 1). Using the 3 categories proposed by ITBCC, 2 budding was significantly related to survival in univariate analysis (p = 0.006) but lost significance in multivariate analysis. Tumor budding showed a prognostically negative impact in glandular EACs. The 8 buds per field cut off appears to provide the best prognostic discriminant. Tumor budding assessment should be added to the identification of other prognostic factors already described in the same series (stage, histotype and vascular invasion). 1

Epidemiology and treatment outcomes of cutaneous squamous cell carcinoma extending to the temporal bone.

Accurate epidemiological and outcomes data regarding cutaneous squamous cell carcinoma (cSCC) extending to the temporal bone is lacking. Retrospective analysis of 167 Australian patients with primary and peri-temporal bone cSCC. cSCC extending from secondary subsites (93.4%) was 14 times more frequent than primary temporal bone SCC (6.6%). For patients who underwent curative surgery ± post-operative radiotherapy (n= 146, 87.4%), 5-year disease-free survival, locoregional recurrence-free survival, disease-specific survival, and overall survival was 53.0%, 59.4%, 67.9%, and 44.7%, respectively. External ear and pre-auricular tumors, salvage surgery, tumor size (≥40 mm medial-lateral), nodal disease, and involved margins were negative predictors of survival in multivariable analysis. In regions of high sun exposure, cSCCs extending to the temporal bone are more common than primary cancers. Outcomes are improved with clear margins, justifying the need for radical resection. Further research regarding pre-auricular cancers is required given poorer associated survival outcomes.

Myasthenia gravis treated in the neurology intensive care unit: a 14-year single-centre experience.

Severe myasthenia gravis (MG) exacerbation with respiratory failure and/or dysphagia usually requires monitoring and treatment in the neurology intensive care unit (NICU). The aim of our study was to identify all patients with severe MG exacerbation treated in the NICU in order to assessed potential factors affecting patients' need for mechanical ventilation, occurrence of complications and the final outcome. We retrospectively included all patients with severe exacerbation of MG who required management in the NICU during a 14-year period. Baseline sociodemographic and clinical features, data on medication, comorbidities and outcome were obtained by reviewing medical records and institutional databases. Our study comprised 130 severe MG exacerbations detected in 118 patients. Median age of patients was 61.5years, and women accounted for 58.5% of the patients. Half of the patients required mechanical ventilation during hospitalization. Lethal outcome was observed in 12.3% of severe MG exacerbations. Only elder age was an independent negative predictor of survival (OR 0.89, 95% CI 0.82-0.97, p < 0.01). Complications during hospitalization were detected in 50% of patients. A higher number of comorbidities (OR 1.09, 95% CI 1.60-2.35, p = 0.01) and mechanical ventilation (OR 28.48, 95% CI 8.56-94.81, p < 0.01) were independent predictors of complications during hospitalization. Patients with a severe MG exacerbation who do not require mechanical ventilation have a good outcome after treatment in the NICU. Elder age is an independent predictor of lethal outcome in patients with severe MG exacerbation. Mechanical ventilation and a higher number of comorbidities lead to more frequent complications.

Overhydration in acute kidney injury: Is it always a menace to critically ill patients? A survival study using bioimpedance spectroscopy.

The hydration status is a predictor of survival in critically ill patients. However, it is unclear whether this association depends on the patient clinical condition. This study was designed to analyze the impact of hydration status on survival of critically ill patients with acute kidney injury (AKI) with or without sepsis. A prospective cohort study following critically ill patients with AKI consecutively admitted over a one-year period to a teaching hospital intensive care unit (ICU). All patients with AKI stage three or higher of the KDIGO score were included. The hydration status was evaluated through the overhydration (OH) parameter of spectroscopy bioimpedance and sepsis was defined according Sepse-3 criteria. The survival analysis used adjusted competing-risks regression. Forty-eight patients were included, 27 (56%) with a sepsis diagnosis. The main negative predictors of survival among sepsis patients, adjusted by SAPS3 score, were higher OH (SHR 1.1, 95% CI 1.0-1.2, p=0.02), mechanical ventilation (SHR 6.9, 95% CI 1.0-47.8, p=0.04) and older age (SHR 1.1, 95% CI 1.0-1.1, p=0.005). The predictors in non-sepsis patients were lower OH (SHR 0.82, 95% CI 0.71-0.95, p=0.008) and mechanical ventilation (SHR 12, 95% CI 2.4-6.6, p<0.001). This finding suggests that extracellular overhydration is an independent predictor of survival in critically ill patients with sepsis, but it seems to have opposite effect in non-sepsis patients.