Multivariate Survival Analysis Research Articles

Separating lymph node stations by the surgeon from the gastric cancer specimen improves the quality of nodal status evaluation

BackgroundIn gastric cancer (GC), the pN-stage is an important prognostic factor influencing treatment. Along with the depth of invasion of the tumor, the presence of nodal metastases is one of the most important prognostic factors guiding treatment strategies in gastric cancer. Examining a small number of lymph nodes may lead to understaging of the disease; hence, it is essential for the nodal status to be precisely assessed. In this study, we explored whether dissecting lymph node stations into separate samples by the surgeon from the gastric cancer surgical specimen affects the quality of nodal status evaluation and patient outcome.MethodsThe clinical data of 130 GC patients treated at the Helsinki University Hospital between 2016 and 2019 was reviewed. The performed operations included 59 total and 71 subtotal gastrectomies. The processing of the surgical specimen before the pathological examination was assessed from the operation records and pathology reports.The association of the number of examined lymph nodes with other variables was assessed, and multivariate survival analysis was performed to explore the independent prognostic factors in disease-specific survival.ResultsDissecting lymph node stations into separate specimens before pathological evaluation yielded a significantly greater number of examined lymph nodes compared with a specimen without intervention (median 34.5 vs 21.0, p < 0.001). The pT-stage, the pN-stage, and the extent of lymphadenectomy were identified as independent prognostic factors, whereas dissecting the specimen’s lymph node stations did not associate with survival.ConclusionsDissecting lymph node stations into separate specimens results in a greater number of examined lymph nodes, which has the potential to lead to a more reliable pN-stage assessment.

Factors associated with adverse outcomes among patients hospitalized at a COVID-19 treatment center in Herat, Afghanistan.

Though many studies on COVID have been published to date, data on COVID-19 epidemiology, symptoms, risk factors and severity in low- and middle-income countries (LMICS), such as Afghanistan are sparse. To describe clinical characteristics, severity, and outcomes of patients hospitalized in the MSF COVID-19 treatment center (CTC) in Herat, Afghanistan and to assess risk factors associated with severe outcomes. 1113 patients were included in this observational study between June 2020 and April 2022. Descriptive analysis was performed on clinical characteristics, complications, and outcomes of patients. Univariate description by Cox regression to identify risk factors for an adverse outcome was performed. Adverse outcome was defined as death or transfer to a level 3 intensive care located at another health facility. Finally, factors identified were included in a multivariate Cox survival analysis. A total of 165 patients (14.8%) suffered from a severe disease course, with a median time of 6 days (interquartile range: 2-11 days) from admission to adverse outcome. In our multivariate model, we identified male gender, age over 50, high O2 flow administered during admission, lymphopenia, anemia and O2 saturation < = 93% during the first three days of admission as predictors for a severe disease course (p<0.05). Our analysis concluded in a relatively low rate of adverse outcomes of 14.8%. This is possibly related to the fact that the resources at an MSF-led facility are higher, in terms of human resources as well as supply of drugs and biomedical equipment, including oxygen therapy devices, compared to local hospitals. Predictors for severe disease outcomes were found to be comparable to other settings.

Overall Survival After Mohs Surgery for Early-Stage Merkel Cell Carcinoma

Merkel cell carcinoma (MCC) is a rare cutaneous malignant neoplasm with increasing incidence and high mortality. Although it is accepted that the optimal treatment for localized tumors is surgical, the data surrounding the optimal surgical approach are mixed, and current National Comprehensive Cancer Network guidelines state that Mohs micrographic surgery (MMS) and wide local excision (WLE) can both be used. The current National Comprehensive Cancer Network guidelines do not advocate a preference for MMS or WLE and suggest that they can be used interchangeably. To evaluate the association of surgical approach with overall survival after excision of localized T1/T2 MCC. This retrospective cohort study used the National Cancer Database to assess adults with T1/T2 MCC who were diagnosed between January 1, 2004, and December 31, 2018, with pathologically confirmed, negative regional lymph nodes and treated with surgery. The National Cancer Database includes all reportable cases from Commission on Cancer-accredited facilities. Data analysis was performed from October 2022 to May 2023. Surgical approach. Overall survival. A total of 2313 patients (mean [SD] age, 71 [10.6] years; 1340 [57.9%] male) were included in the study. Excision with MMS had the best unadjusted survival, with mean (SE) survival rates of 87.4% (3.4%) at 3 years, 84.5% (3.9%) at 5 years, and 81.8% (4.6%) at 10 years vs 86.1% (0.9%) at 3 years, 76.9% (1.2%) at 5 years, and 60.9% (2.0%) at 10 years for patients treated with WLE. Patients treated with narrow-margin excision had similar survival as those treated with WLE, with mean (SE) survival rates of 84.8% (1.4%) at 3 years, 78.3% (1.7%) at 5 years, and 60.8% (3.6%) at 10 years. On multivariable survival analysis, excision with MMS was associated with significantly improved survival compared with WLE (hazard ratio, 0.59; 95% CI, 0.36-0.97; P = .04). High-volume MCC centers were significantly more likely to use MMS over WLE compared with other centers (odds ratio, 1.99; 95% CI, 1.63-2.44; P < .001). In this cohort study, the use of MMS (compared with WLE) was associated with significantly improved survival for patients with localized MCC with pathologically confirmed negative lymph nodes treated with surgery. These data suggest that Mohs surgery may provide a more effective treatment for MCC primary tumors than conventional WLE, although the lack of randomization and potential for selection bias in this study highlight the need for future prospective work evaluating this issue.

Phencyclidine Positivity on Urine Drug Screening in Patients Treated for Alcohol Withdrawal on a Dual-diagnosis Medically Assisted Withdrawal Unit.

Little contemporary research has explored phencyclidine (PCP) use in people with alcohol use disorder. Therefore, we sought to determine the prevalence of PCP positivity on urine toxicology screening among patients admitted for alcohol withdrawal, identify correlates of PCP positivity, and investigate PCP positivity's relationship to length of stay (LOS) and risk of facility readmission. This was a retrospective study of patients admitted to a dual-diagnosis medically assisted withdrawal unit for alcohol withdrawal from 2014 to 2019. Univariate tests and logistic regression were used to investigate potential correlates of PCP positivity on admission toxicology screening (primary outcome). Multivariable linear regression models and survival analyses analyzing LOS and risk of readmission (secondary outcomes) were also developed. Ninety of 3731 patients (2.4%) screened positive for PCP. There were significant associations on univariate testing between PCP positivity and age, race, homeless status, and urine toxicology positivity for amphetamines, benzodiazepines, barbiturates, cocaine, tetrahydrocannabinol, and oxycodone. On multivariate logistic regression, only tetrahydrocannabinol, barbiturates, and cocaine positivity were associated with PCP positivity. Multivariate logistic regression and survival analysis found no statistically significant associations between PCP positivity and LOS or risk of readmission. This study provides rare analysis of contemporary data on PCP use among patients undergoing medically assisted alcohol withdrawal. Phencyclidine positivity was uncommon, but use appears considerably higher among this patient population than the general population. There was no significant association between PCP positivity and LOS or readmission risk.

High-grade tumor budding is a risk factor for survival in patients with laryngeal squamous cell carcinoma

ObjectiveWith the increasing incidence and mortality of laryngeal squamous cell carcinoma worldwide, researchers continue to search for novel prognostic factors and treatment methods for preventing early laryngeal squamous cell carcinoma from becoming advanced laryngeal squamous cell carcinoma. This study aims to determine if tumor budding is an independent risk factor associated with the survival of patients with laryngeal squamous cell carcinoma. Methods268 cases of laryngeal squamous cell carcinoma were studied, and tumor budding was analyzed for associations with clinicopathological features and clinical outcomes. ResultsTumor budding was divided into low-grade tumor budding (0–6/0.785 mm2) and high-grade tumor budding (≥7/0.785 mm2) based on the results of the receiver operating characteristics curve analysis. Logistic regression analysis showed that smaller tumor cell nests, the low levels of tumor-infiltrating lymphocytes, and higher pathological T staging were the risk factors for high-grade tumor budding (p < 0.05). In the low-grade tumor budding group, there was no statistic difference in survival between patients without tumor budding and those with 1–6/0.785 mm2 tumor budding. Multivariate survival analysis showed high-grade tumor budding (p < 0.001) was independent prognostic factors for disease-free survival and overall survival in laryngeal squamous cell carcinoma. High-grade tumor budding was also an independent prognostic factor for disease-free survival (p = 0.037) and overall survival (p = 0.009) in T1-2N0 laryngeal squamous cell carcinoma. ConclusionsSmaller tumor cell nests, the low levels of tumor-infiltrating lymphocytes, and higher pathological T staging were closely associated with high-grade tumor budding in laryngeal squamous cell carcinoma. High-grade tumor budding may be an adverse risk factor that affects not only the disease-free survival and overall survival of laryngeal squamous cell carcinoma patients but also the survival of T1-2N0 laryngeal squamous cell carcinoma patients. Level of EvidenceLevel 4.

Real-world survival outcomes of wedge resection versus lobectomy for cT1a/b cN0 cM0 non-small cell lung cancer: a single center retrospective analysis.

JCOG0802/WJOG4607L showed benefits in overall survival (OS) of segmentectomy. CALGB 140503 confirmed that sublobar resection was not inferior to lobectomy concerning recurrence-free survival (RFS) but did not provide specific OS and RFS according to the techniques of sublobar resections. Hence, we retrospectively analyze the survival differences between wedge resection and lobectomies for stage IA lung cancer. We reviewed the clinical records of patients with clinical stage IA NSCLC over 20 years. The inclusion criteria were: preoperative staging with CT scan and whole body CT/PET; tumor size <20mm; wedge resections or lobectomies with or without lymph node dissection; NSCLC as the only primary tumor during the follow-up period. We excluded: multiple invasive lung cancer; positive resection margin; preoperative evidence of nodal disease; distant metastasis at presentation; follow-up time <5 years. The reverse Kaplan - Meier method estimated the median OS and PFS and compared them by the log-rank test. The stratified backward stepwise Cox regression model was employed for multivariable survival analyses. 539 patients were identified: 476 (88.3%) lobectomies and 63 (11.7%) wedge resections. The median OS time for the whole cohort was 189.7 months (range: 173.7 - 213.9 months). The 5-year wedge resection and lobectomy OS were 82.2% and 87.0%. The 5-year RFS of wedge resection and lobectomy were 17.8% and 28.9%. The log-rank test showed no significant differences (p = 0.39) between wedge resections and lobectomies regarding OS and RFS (p = 0.23). Lobectomy and wedge resection are equivalent oncologic treatments for individuals with cN0/cM0 stage IA NSCLC <20mm. Validating the current findings requires a prospective, randomized comparison between wedge resection and standard lobectomy to establish the prognostic significance of wedge resection.

A STUDY OF MMP7 EXPRESSION IN TRIPLE NEGATIVE BREAST CANCER PATIENTS

MMP7 has a part in preventing apoptosis and promoting angiogenesis. According to both in vivo and in vitro evidence, MMP7 is mostly seen during tumour invasion and metastasis. Controlling MMP7 expression may be a method for treating this cancer because its overexpression encourages the occurrence, progression, and invasiveness of breast cancer. The aim is to study the expression of MMP7 in triple negative breast cancer patients. Formalin fixed paraffin embedded breast tumor tissues from 50 triple negative breast cancer patients were collected for this study. immunohistochemistry method was used to study MMP7 expression and correlated with clinical and pathological parameters as well as disease status. MMP7 positivity was observed in 48% triple negative breast cancer patients. No significant correlation of MMP7 expression with age, menopausal status, tumour size, histopathology, stage and lymph node status were observed. A significant higher incidence of MMP7 expression was noted in patients with high grade tumor (63%) as compared to patients with low grade tumor (00%). Further, a significant higher incidence of MMP7 was observed in patients with high BR score (65%) as compared to the patients with low BR score (00%). Also, a significant higher incidence was observed in patients with relapse (63%) than patients in remission (35%). A significant higher incidence of MMP7 expression was observed with respect to disease free survival in univariate survival analysis. In multivariate survival analysis, for disease free survival MMP7 entered at step 1 and lymph node status and MMP7 entered at step 2. The findings imply that MMP7 is important for tumour invasion and metastasis, and that elevated MMP7 expression is associated with tumour development and recurrence.

Postpartum longissimus dorsi muscle loss, but not back fat, is associated with resumption of postpartum ovarian activity in dairy cattle

The objectives of this observational cohort study were to assess the effect of body condition score change, back fat depth change, and muscle diameter change on the time to commencement of luteal activity and first estrus in commercial pedigree Holstein cows. One hundred and 40 of 200 commercial pedigree Holstein cows were enrolled in one dairy herd in Somerset, United Kingdom, over 52 weeks in 2021-22. The herd used 4 automatic milking machines with in-line progesterone measurement capability to determine commencement of luteal activity and time to first estrus. Cows were followed until at least 60 d postpartum and milk progesterone measured daily starting from 10 DIM. Body condition scoring and ultrasound measurements of back fat depth and Longissimus dorsi muscle diameter were performed on cows twice: within 7 d of both calving and 60 DIM. Other explanatory variables assessed included parity, 60-d and 305-d milk yield, and subclinical ketosis (β-hydroxybutryate (βHB) ≥ 1.2mmol/L). Occurrence of clinical disease <60 DIM was forced into all models as a binary variable. Data were analyzed using multivariable cox proportionate survival analyses. Muscle loss was associated with commencement of luteal activity and time to first estrus. A reduction in muscle diameter by 1.5 to 5 mm was associated with the shortest time to the start of luteal activity and first estrus. A reduction in muscle diameter >8 mm was associated with the longest times to luteal activity and first estrus. In addition to being affected by muscle loss, commencement of luteal activity was delayed by subclinical ketosis, clinical disease, and failure to gain body condition to 60 DIM. Cows that had a BCS loss of 0.25 or more between calving and 60 DIM were at least 52 ± 22% less likely to have commenced luteal activity compared with those that gained BCS. Interestingly, cows that had no change in body condition score commenced luteal activity later than those that gained body condition score. Muscle loss was associated with time to first estrus irrespective of clinical disease status. Cows that lost > 8 mm of muscle diameter showed estrus behavior later than cows that lost 1.5 to 5 mm. In conclusion, our findings indicate that extensive muscle loss postpartum was associated with a delayed start to luteal activity and first estrus irrespective of body condition change, clinical disease, and subclinical ketosis. Marginal muscle loss and a gain in body condition, however, were associated with an earlier start to luteal activity and first estrus.

Risk factors for inpatient mortality among children with severe acute malnutrition in Zimbabwe and Zambia

Background/ObjectivesMalnutrition underlies 45% of deaths in children under-5 years annually. Children hospitalised with complicated severe acute malnutrition (SAM) have unacceptably high mortality. We aimed to identify variables from early hospital admission (baseline factors) independently associated with inpatient mortality in this cohort to identify those most at risk.Subjects/MethodsObservational study of 745 children aged 0–59 months admitted with complicated SAM at three hospitals in Zimbabwe/Zambia. Children underwent anthropometry and clinical assessment by a study physician within 72 h of enrolment, and caregivers provided sociodemographic data. Children were followed-up daily until discharge/death. A multivariable survival analysis identified the baseline factors independently associated with mortality.Results70/745 (9.4%) children died in hospital. Age between 6–23 months [aHR 6.53, 95%CI 2.24–19.02], higher mid-upper arm circumference [aHR 0.73, 95%CI 0.59–0.89], presence of oedema [aHR 2.22, 95%CI 1.23–4.05], shock [aHR 8.18, 95%CI 3.79–17.65], sepsis [aHR 3.13, 95%CI 1.44–6.80], persistent diarrhoea [aHR 2.27, 95%CI 1.18–4.37], lack of a toilet at home [aHR 4.35, 95%CI 1.65–11.47], and recruitment at one Harare site [aHR 0.38, 95%CI 0.18–0.83] were all independently associated with inpatient mortality. Oedematous children had a significantly higher birthweight [2987 g vs 2757 g, p < 0.001] than those without oedema; higher birthweight was weakly associated with mortality [aHR 1.50 95%CI 0.97–2.31].ConclusionsChildren with oedema, low MUAC, baseline infections, shock and lack of home sanitation had a significantly increased risk of inpatient mortality following hospitalisation for complicated SAM. Children with high-risk features may require additional care. A better understanding of the pathophysiology of SAM is needed to identify adjunctive interventions.

Longitudinal detection of subcategorized CD44v6+ CTCs and circulating tumor endothelial cells (CTECs) enables novel clinical stratification and improves prognostic prediction of small cell lung cancer: A prospective, multi-center study

Current management of small cell lung cancer (SCLC) remains challenging. Effective biomarkers are needed to subdivide patients presenting distinct treatment response and clinical outcomes. An understanding of heterogeneous phenotypes of aneuploid CD31- circulating tumor cells (CTCs) and CD31+ circulating tumor endothelial cells (CTECs) may provide novel insights in the clinical management of SCLC. In the present translational and prospective study, increased cancer metastasis-related cell proliferation and motility, accompanied with up-regulated mesenchymal marker vimentin but down-regulated epithelial marker E-cadherin, were observed in both lentivirus infected SCLC and NSCLC cells overexpressing the stemness marker CD44v6. Aneuploid CTCs and CTECs expressing CD44v6 were longitudinally detected by SE-iFISH in 120 SCLC patients. Positive detection of baseline CD44v6+ CTCs and CD44v6+ CTECs was significantly associated with enhanced hepatic metastasis. Karyotype analysis revealed that chromosome 8 (Chr8) in CD44v6+ CTCs shifted from trisomy 8 towards multiploidy in post-therapeutic patients compared to pre-treatment subjects. Furthermore, the burden of baseline CD44v6+ CTCs (t0) or amid the therapy (t1-2), the ratio of baseline CD31+ CTEC/CD31- CTC (t0), and CTC-WBC clusters (t0) were correlated with treatment response and distant metastases, particularly brain metastasis, in subjects with limited disease (LD-SCLC) but not in those with extensive disease (ED-SCLC). Multivariate survival analysis validated that longitudinally detected CD44v6+/CD31- CTCs was an independent prognostic factor for inferior survival in SCLC patients. Our study provides evidence for the first time that comprehensive analyses of CTCs, CTECs, and their respective CD44v6+ subtypes enable clinical stratification and improve prognostic prediction of SCLC, particularly for potentially curable LD-SCLC.

Overexpression of ferritin light chain as a poor prognostic factor for breast cancer.

Ferritin light chain (FTL) is involved in tumor progression, but the specific molecular processes by which FTL affects the development of breast cancer (BRCA) have remained unknown. In this research, the clinicopathological significance of FTL overexpression in BRCA was investigated. To investigate the role of FTL in BRCA, we utilized multiple online databases to analyse FTL expression levels in BRCA. Next, we reviewed the expression and localization of the FTL protein in BRCA by immunohistochemistry (IHC), Western blot (WB) and immunofluorescence (IF) staining. To assess the impact of FTL on patient prognosis, we conducted Kaplan‒Meier, univariate and multivariate survival analyses. The relationship between FTL and immune infiltration in BRCA was also analysed in the TISCH and SangerBox databases. MTT, malondialdehyde (MDA) and reactive oxygen species (ROS) assays were carried out to investigate the molecular mechanisms of FTL action in BRCA cells. FTL was significantly upregulated in BRCA compared to normal tissues. Its expression significantly linked to histological grade (P = 0.038), PR expression (P = 0.021), Her2 expression (P = 0.012) and Ki-67 expression (P = 0.040) in patients with BRCA. Furthermore, the expression of the FTL protein was higher in the BRCA cell lines than in the normal breast cells and mainly localized in the cytoplasm. Compared to patients with a low level of FTL expression, patients with a high level of FTL expression showed lower overall survival (OS). More convincingly, univariate and multivariate statistical analyses revealed that FTL expression (P = 0.000), ER expression (P = 0.036) and Her2 expression (P = 0.028) were meaningful independent prognostic factors in patients with BRCA. FTL was associated with immune infiltration in BRCA. Functional experiments further revealed that FTL knockdown inhibited the capacity of proliferation and increased the level of oxidative stress in BRCA cells. Overexpression of FTL was associated with the progression of BRCA. FTL overexpression may become a biomarker for the evaluation of poor prognosis in patients with BRCA.

Identifying clinicopathological risk factors for regional lymph node metastasis in Chinese patients with T1 breast cancer: a population-based study.

To analyze clinicopathological risk factors and regular pattern of regional lymph node metastasis (LNM) in Chinese patients with T1 breast cancer and the effect on overall survival (OS) and disease-free survival (DFS). Between 1999 and 2020, breast cancer patients meeting inclusion criteria of unilateral, no distant metastatic site, and T1 invasive ductal carcinoma were reviewed. Clinical pathology characteristics were retrieved from medical records. Survival analysis was performed using Kaplan-Meier methods and an adjusted Cox proportional hazards model. We enrolled 11,407 eligible patients as a discovery cohort to explore risk factors for LNM and 3484 patients with stage T1N0 as a survival analysis cohort to identify the effect of those risk factors on OS and DFS. Compared with patients with N- status, patients with N+ status had a younger age, larger tumor size, higher Ki67 level, higher grade, higher HR+ and HER2+ percentages, and higher luminal B and HER2-positive subtype percentages. Logistic regression indicated that age was a protective factor and tumor size/higher grade/HR+ and HER2+ risk factors for LNM. Compared with limited LNM (N1) patients, extensive LNM (N2/3) patients had larger tumor sizes, higher Ki67 levels, higher grades, higher HR- and HER2+ percentages, and lower luminal A subtype percentages. Logistic regression indicated that HR+ was a protective factor and tumor size/higher grade/HER2+ risk factors for extensive LNM. Kaplan-Meier analysis indicated that grade was a predictor of both OS and DFS; HR was a predictor of OS but not DFS. Multivariate survival analysis using the Cox regression model demonstrated age and Ki67 level to be predictors of OS and grade and HER2 status of DFS in stage T1N0 patients. In T1 breast cancer patients, there were several differences between N- and N+ patients, limited LNM and extensive LNM patients. Besides, HR+ plays a dual role in regional LNM. In patients without LNM, age and Ki67 level are predictors of OS, and grade and HER2 are predictors of DFS.

Prognostic Value of TSPO PET Before Radiotherapy in Newly Diagnosed IDH-Wild-Type Glioblastoma.

The 18-kDa translocator protein (TSPO) is gaining recognition as a relevant target in glioblastoma imaging. However, data on the potential prognostic value of TSPO PET imaging in glioblastoma are lacking. Therefore, we investigated the association of TSPO PET imaging results with survival outcome in a homogeneous cohort of glioblastoma patients. Methods: Patients were included who had newly diagnosed, histologically confirmed isocitrate dehydrogenase (IDH)-wild-type glioblastoma with available TSPO PET before either normofractionated radiotherapy combined with temozolomide or hypofractionated radiotherapy. SUVmax on TSPO PET, TSPO binding affinity status, tumor volumes on MRI, and further clinical data, such as O 6-alkylguanine DNA methyltransferase (MGMT) and telomerase reverse transcriptase (TERT) gene promoter mutation status, were correlated with patient survival. Results: Forty-five patients (median age, 63.3 y) were included. Median SUVmax was 2.2 (range, 1.0-4.7). A TSPO PET signal was associated with survival: High uptake intensity (SUVmax > 2.2) was related to significantly shorter overall survival (OS; 8.3 vs. 17.8 mo, P = 0.037). Besides SUVmax, prognostic factors for OS were age (P = 0.046), MGMT promoter methylation status (P = 0.032), and T2-weighted MRI volume (P = 0.031). In the multivariate survival analysis, SUVmax in TSPO PET remained an independent prognostic factor for OS (P = 0.023), with a hazard ratio of 2.212 (95% CI, 1.115-4.386) for death in cases with a high TSPO PET signal (SUVmax > 2.2). Conclusion: A high TSPO PET signal before radiotherapy is associated with significantly shorter survival in patients with newly diagnosed IDH-wild-type glioblastoma. TSPO PET seems to add prognostic insights beyond established clinical parameters and might serve as an informative tool as clinicians make survival predictions for patients with glioblastoma.

Performance of DNA-based biomarkers for classification of adrenocortical carcinoma: a prognostic study.

Adrenocortical carcinoma (ACC) is a rare aggressive malignancy with heterogeneous clinical outcomes. Recent studies proposed a combination of clinical/histopathological parameters (S-GRAS score) or molecular biomarkers (BMs) to improve prognostication. We performed a comparative analysis of DNA-based BMs by evaluating their added prognostic value to the S-GRAS score. A total of 194 formalin-fixed, paraffin-embedded (FFPE) ACC samples were analysed, including a retrospective training cohort (n = 107) and a prospective validation cohort (n = 87). Targeted DNA sequencing and pyrosequencing were used to detect somatic single-nucleotide variations in ACC-specific genes and methylation in the promoter region of paired box 5 (PAX5). The European Network for the Study of Adrenocortical Tumors (ENSAT) tumour stage, age, symptoms at presentation, resection status, and Ki-67 were combined to calculate S-GRAS. Endpoints were overall (OS), progression-free (PFS), and disease-free survival (DFS). Prognostic role was evaluated by multivariable survival analysis and their performance compared by Harrell's concordance index (C index). In training cohort, an independent prognostic role was confirmed at multivariate analysis for two DNA-based BMs: alterations in Wnt/β-catenin and Rb/p53 pathways and hypermethylated PAX5 (both P< .05 for PFS and DFS, hazard ratio [HR] 1.47-2.33). These were combined to S-GRAS to obtain a combined (COMBI) score. At comparative analysis, the best discriminative prognostic model was COMBI score in both cohorts for all endpoints, followed by S-GRAS score (C index for OS 0.724 and 0.765, PFS 0.717 and 0.670, and DFS 0.699 and 0.644, respectively). Targeted DNA-based BM evaluated on routinely available FFPE samples improves prognostication of ACC beyond routinely available clinical and histopathological parameters. This approach may help to better individualise patient's management.

Evaluating Rates of Positive Margins After Standard Excision of Cutaneous Adnexal Malignancies.

It is recommended to excise adnexal neoplasms with standard local excision or Mohs micrographic surgery (MMS), although many occur on high-risk sites such as the head and neck (H&N) and exhibit subclinical extension. Minimal evidence exists on the efficacy of standard excisions for these tumors. To evaluate the rate of positive surgical margins after standard excision of adnexal tumors. Retrospective cohort study of cutaneous adnexal malignancies from the National Cancer Database diagnosed from 2004 to 2019. The authors identified a total of 4,402 cases treated with standard excision. Tumors on the H&N were approximately twice as likely as those on the trunk and extremities (T&E) to be excised with positive margins (odds ratio 2.146, p < .001), with the highest estimated rate for eccrine adenocarcinoma (12.1%, SE: 2.3%). The subtype with the highest positive margin rate on the T&E was microcystic adnexal carcinoma (8.0%, SE: 2.9). Positive margins were associated with poorer overall survival on multivariable survival analysis (hazard ratio 1.299, p = .015). The authors present subtype- and site-specific positive margin rates for adnexal tumors treated with standard excision, which suggest that tumors on the H&N and some T&E subtypes, should be considered for MMS.

A novel pathological finding, "BABA", for a prognostic factor in oral tongue carcinoma.

92 Background: Oral tongue carcinoma is one of the cancers with poor prognosis. The UICC staging classification is commonly used to predict outcomes and to select the treatments, although there are cases where cancer relapse early despite being at the same Stages, indicating a need for additional prognostic factors to predict patient outcomes accurately. Recent advances in RNA sequencing of tumor and immune cells, as well as elucidation of the tumor microenvironment, have enabled the identification of many genes associated with recurrence risk and immunosuppressive environment around the tumor, which essential for precision treatment of the patients with high risks of recurrence. However pathological findings remain the first step in selecting samples with a high risk of recurrence for further analysis of RNA sequencing or the tumor microenvironment. In this study, we identified a novel pathological feature named as “BABA” (Broadening Amoeboid Behavior of Advanced tumor cells) that appears around the invasive front of tumors. It describes the way in which cancer cells progress like amoeba between muscle fibers and affect the prognosis of oral tongue carcinoma, making it a potential factor for the future analysis of next-generation sequencing or tumor microenvironment. Methods: Patients with oral tongue squamous cell carcinoma who underwent surgery were recruited, excluding those who had received salvage treatment for recurrence, those with simultaneous occurrence of carcinoma, those who had undergone palliative therapy, postoperative therapy, or those who lacked any pathological findings. Survival analyses for existing pathological findings, such as pT (pathological primary stage), pN (pathological nodal stage), ENE (extra nodal extension) status, lymphatic invasion, venous invasion, perineural extension, margin status, WPOI (worst pattern of invasion) and BABA were conducted. Results: A total number of 211 patients were analyzed in this study. Patients with positive for BABA had a two-year overall survival rate and recurrence-free survival rate of 0.78(p=0.02) and 0.39 (p&lt;0.001), respectively, according to Kaplan-Meier analysis. In the multivariate analysis for overall survival using Cox regression model, venous invasion and pN ≥1 were significant prognostic factors, with HR (95%CI) of 3.0 (1.5-6.3) and 2.4 (1.2-4.5), respectively. In the multivariate analysis for recurrence free survival using Cox regression model, positive for lymphatic invasion, venous invasion, BABA, pN ≥1 were significant factors, with HR (95%CI) of 2.1 (1.2-3.6), 2.0 (1.1-3.4), 2.2 (1.3-3.7) and 2.0 (1.2-3.6), respectively. Conclusions: BABA is the novel risk factor for recurrence in oral tongue carcinoma. Identifying BABA could help clinicians better predict recurrence and develop more personalized treatment strategies.

The Impact of Histological Variants on Oncological Outcomes in Patients with Muscle Invasive Bladder Cancer Treated with Radical Cystectomy.

Bladder cancer is a heterogeneous entity characterized by a wide range of different morphologies. The aim of this study was to investigate the prognostic effect of bladder tumor with variant histology that is treated with radical cystectomy on oncological outcomes. One hundred eighty-six patients who underwent radical cystectomy between September 2001 and June 2020 were included in the study. The patients were divided into 2 groups variant histology group (n = 54) and transitional cell cancer group (n = 132). Clinicopathologic data were compared between the two groups. The groups were similar in terms of demographic characteristics. In the mul- tivariate analysis of cancer-specific survival in transitional cell cancer against variant histology, high-grade detection of primary transurethral bladder tumor pathology, cystectomy pT, cystectomy positive lymph node, and positive surgical margin in cys- tectomy were determined to be statistically significant. Diagnosis of pT2 and high grade of primary transurethral bladder tumor pathology, cystectomy ≥ pT3, cystec- tomy positive lymph node, and positive surgical margin in cystectomy were statis- tically significant in multivariate analysis of overall survival. Cancer-specific survival time was estimated at 65.1 ± 8.3 months for variant histology and 134.2 ± 10.4 months for transitional cell cancer (P=.004). The estimated overall survival time was 61.9 ± 8.0 months in variant histology and 119.0 ± 9.8 months in transitional cell cancer (P = .014). Pathological features and prognosis of bladder cancer with variant histol- ogies are worse than those of pure urothelial bladder cancer. Overall survival and can- cer-specific survival are shorter in bladder cancer with variant histology than in pure urothelial bladder cancer. Following the diagnosis of variant histology in transurethral bladder tumor, poor prognosis must be considered in the treatment plan.

Neighborhood Childhood Opportunity, Race/Ethnicity, and Surgical Outcomes in Children With Congenital Heart Disease

BackgroundRacial and ethnic disparities in outcomes for children with congenital heart disease (CHD) coexist with disparities in educational, environmental, and economic opportunity. ObjectivesWe sought to determine the associations between childhood opportunity, race/ethnicity, and pediatric CHD surgery outcomes. MethodsPediatric Health Information System encounters aged <18 years from 2016 to 2022 with International Classification of Diseases-10th edition codes for CHD and cardiac surgery were linked to ZIP code-level Childhood Opportunity Index (COI), a score of neighborhood educational, environmental, and socioeconomic conditions. The associations of race/ethnicity and COI with in-hospital surgical death were modeled with generalized estimating equations and formal mediation analysis. Neonatal survival after discharge was modeled by Cox proportional hazards. ResultsOf 54,666 encounters at 47 centers, non-Hispanic Black (Black) (OR: 1.20; P = 0.01), Asian (OR: 1.75; P < 0.001), and Other (OR: 1.50; P < 0.001) groups had increased adjusted mortality vs non-Hispanic Whites. The lowest COI quintile had increased in-hospital mortality in unadjusted and partially adjusted models (OR: 1.29; P = 0.004), but not fully adjusted models (OR: 1.14; P = 0.13). COI partially mediated the effect of race/ethnicity on in-hospital mortality between 2.6% (P = 0.64) and 16.8% (P = 0.029), depending on model specification. In neonatal multivariable survival analysis (n = 13,987; median follow-up: 0.70 years), the lowest COI quintile had poorer survival (HR: 1.21; P = 0.04). ConclusionsChildren in the lowest COI quintile are at risk for poor outcomes after CHD surgery. Disproportionally increased mortality in Black, Asian, and Other populations may be partially mediated by COI. Targeted investment in low COI neighborhoods may improve outcomes after hospital discharge. Identification of unmeasured factors to explain persistent risk attributed to race/ethnicity is an important area of future exploration.

Childhood Grave’s-an experience from a tertiary care center

Background: Graves’ disease (GD) attributes for important cause for childhood hyperthyroidism with a prevalence of 0.02%. Initial treatment for GD is the use of antithyroid drugs (ATDs), which is well accepted. The remission rate is around about 30% of children treated with ATD. Aims and Objective: (1) To assess the predictors of relapse and remission after ATD in children with Grave’s disease. (2) To study the clinical profile at presentation and treatment outcome of children with Grave’s disease. Materials and Methods: We conducted a prospective cohort study of children diagnosed for GD (n=27) and treated with either carbimazole (0.6–0.8 mg/kg), methimazole (0.2–1 mg/kg), or (propylthiouracil, 5–10 mg/kg) and continued till euthyroid state was achieved. The dose was titrated every 2 months once till the achievement of the euthyroid state. Assessment of remission and relapse was done within a year of stopping the drug. Results: The overall estimated relapse rate for hyperthyroidism was 54.1% (13 patients), within a year of stopping ATD with a mean duration treatment of 24.23±7.44 months. Multivariate survival analysis showed that the risk of relapse (87.5%) was higher for patients of a body mass index SD score &lt;0.5 and a large goiter. Pre-pubertal patients had higher relapse rate than pubertal patients (OR- 3.24, P=0.04). No other clinical variables such as age, gender, and Wayne Index were significantly associated with relapse, though patients in the relapse group were younger, and had a male predominance with higher Wayne index scores. Conclusion: GD in children has a high relapse rate. Severity of the disease as measured by various clinical methods is important in predicting relapse.

Management and Long-term Outcomes of Adults With Medulloblastoma: A Single-Center Experience.

Medulloblastomas are embryonal tumors predominantly affecting children. Recognition of molecularly defined subgroups has advanced management. Factors influencing the management and prognosis of adult patients with medulloblastoma remains poorly understood. We examined the management, prognostic factors, and, when possible, molecular subgroup differences (subset) in adult patients (aged 18 years or older) with medulloblastoma from our center (specialty Neuro-Oncology clinic within a large academic practice) diagnosed between 1992 and 2020. Molecular subtyping corresponding to the 2021 WHO Classification was performed. Kaplan-Meier estimates (with log-rank test) were performed for univariate survival analysis with Cox regression used for multivariate analyses. We included 76 adult patients with medulloblastoma (62% male), with a median age of 32 years at diagnosis (range: 18-66) and median follow-up of 7.7 years (range: 0.6-27). A subset of 58 patients had molecular subgroup characterization-37 SHH-activated, 12 non-WNT/non-SHH, and 9 WNT-activated. Approximately 67% underwent gross total resection, 75% received chemotherapy at diagnosis, and 97% received craniospinal irradiation with boost. The median overall survival (OS) for the whole cohort was 14.8 years. The 2-, 5-, and 10-year OS rates were 93% (95% CI 88-99), 86% (78-94), and 64% (53-78), respectively. Survival was longer for younger patients (aged 30 years or older: 9.9 years; younger than 30 years: estimated >15.4 years; log-rank p < 0.001). There was no survival difference by molecular subgroup or extent of resection. Only age at diagnosis remained significant in multivariate survival analyses. We report one of the largest retrospective cohorts in adult patients with medulloblastoma with molecular subtyping. Survival and molecular subgroup frequencies were similar to prior reports. Survival was better for adult patients younger than 30 years at diagnosis and was not significantly different by molecular subgroup or management characteristics (extent of resection, RT characteristics, or chemotherapy timing or regimen).