Prognostic Factor For Disease-free Survival Research Articles

Impact of TP53-induced glycolysis and apoptosis regulator on malignant activity and resistance to ferroptosis in intrahepatic cholangiocarcinoma.

TP53-induced glycolysis and apoptosis regulator (TIGAR) is an important gene that encodes a regulatory enzyme of glycolysis and reactive oxygen species (ROS) detoxification and is associated with worse prognosis in various cancers. Ferroptosis is a recently identified type of programmed cell death that is triggered by iron-dependent lipid peroxidation. There are no reports on the prognostic impact of TIGAR on intrahepatic cholangiocarcinoma (ICC), and its role in ferroptosis is unclear. Ninety ICC patients who had undergone hepatic resection were enrolled. Immunohistochemical staining for TIGAR was performed. The regulation of malignant activity by TIGAR and the association between ferroptosis and TIGAR were investigated in vitro. Twenty-two (24.4%) patients were categorized into TIGAR-high and -low groups by immunohistochemical staining. There were no noticeable differences in background factors between the two groups, but TIGAR positivity was an independent prognostic factor in disease-free survival (hazard ratio [HR], 2.00; 95% confidence interval [CI], 1.04-3.85, p = 0.0378) and overall survival (HR, 2.10; 95% CI, 1.03-4.30, p = 0.00422) in a multivariate analysis. In vitro, TIGAR knockdown (KD) decreased cell motility (cell proliferation/migration/invasion/colony-forming capabilities) and elevated ROS and lipid peroxidation. This indicated that TIGAR KD induced ferroptosis. TIGAR KD-induced ferroptosis was suppressed using liproxstatin. TIGAR KD decreased the expression of glutathione peroxidase 4, known as factor-suppressing ferroptosis. The combination of TIGAR KD with cisplatin significantly induced more ferroptosis. In conclusion, TIGAR is associated with poor outcomes in ICC patients and resistance to ferroptosis.

Real world data of recurrent and survival rates of penile cancer patients in Songklanagarind hospital: Tumor stage as a predictor for disease-free survival.

This study investigated disease-free survival and oncological outcomes in penile cancer patients treated surgically at a high-volume center and identified the prognostic factors for disease-free survival. A retrospective analysis was conducted on primary penile cancer patients diagnosed and treated at Songklanagarind Hospital, Thailand, between January 2001 and December 2021. Disease-free survival (DFS) was assessed using Kaplan-Meier survival curves, and Cox proportional hazard models were used for multivariate analysis. The study included 188 patients with primary penile cancer. The majority (98.4%) were uncircumcised. Tumor staging revealed 40.6% with T1 tumors, 72.9% with well-differentiated tumors, and 23.5% diagnosed at stage IIIA. The recurrence rate was 19.1%, with a mean time to recurrence of 25.9 months. Disease-free survival rates at 1, 3, and 5 years were 81.1%, 70.9%, and 70.9%, respectively. Median overall survival was 16.43 months, with survival rates at 1, 3, and 5 years at 67.7%, 42.7%, and 35.4%, respectively. Cox proportional hazard models showed significant associations between disease-free survival and a higher T stage, a high level of CRP (>15 mg/L), delayed onset of symptoms, primary lesion location, groin node metastasis, lymphovascular invasion, and pelvic lymph node metastases. However, multivariate analysis revealed that a higher primary tumor stage (T) was the only independent prognostic factor for disease-free survival. This study presents one of the largest cohorts investigating disease-free survival outcomes in penile cancer treatment at a single institution over a prolonged period. A higher pathologic T stage is a significant prognostic factor for disease-free survival. Further large-scale prospective studies are needed for validation.

Prognostic Impact of Mucinous Adenocarcinoma in Stage II and III Colon Cancer.

Mucinous adenocarcinoma is a rare histologic feature of colorectal cancer and is characterized by oncologic features that are different from those of adenocarcinoma. However, there are conflicting views regarding the prognostic impact of mucinous adenocarcinoma on colon cancer. This study aimed to evaluate the prognostic impact of mucinous adenocarcinoma in stage II and III colon cancer. This was a retrospective cohort study. This study was conducted between January 2010 and December 2015. Patients were divided into the mucinous adenocarcinoma and nonmucinous adenocarcinoma groups. Disease-free survival and overall survival were assessed using propensity score matching. Overall, 2532 patients who underwent radical surgery for stage II and III colon cancer were included in the study. The main outcome measures were disease-free survival and overall survival. The median follow-up duration was 86 months. The disease-free survival and overall survival were significantly lower in the mucinous adenocarcinoma group than in the nonmucinous adenocarcinoma group. In subgroup analysis, there was no significant difference in the disease-free survival and overall survival between patients with and without mucinous adenocarcinoma with stage II colon cancer. In stage III colon cancer, the disease-free survival and overall survival were significantly lower in patients with mucinous adenocarcinoma than in those without mucinous adenocarcinoma. Multivariable analysis showed that mucinous adenocarcinoma was a poor prognostic factor for disease-free survival and overall survival. The study's limitations include those that are inherently associated with retrospective single-center studies. Mucinous adenocarcinoma is a poor prognostic factor in stage III but not in stage II colon cancer. Therefore, mucinous adenocarcinoma might not be regarded as an independent risk factor requiring chemotherapy for favorable oncologic outcomes. However, for stage III colon cancer, patients with mucinous adenocarcinoma require close observation. ANTECEDENTES:El adenocarcinoma mucinoso es una característica histológica rara del cáncer colorrectal, se caracteriza por propiedades oncológicas que son diferentes a las del adenocarcinoma. Sin embargo, existen puntos de vista contradictorios con respecto al impacto pronóstico del adenocarcinoma mucinoso en el cáncer de colon.OBJETIVO:Este estudio tuvo como objetivo evaluar el impacto pronóstico del adenocarcinoma mucinoso en las etapas II y III de cáncer de cólon.DISEÑO Y CONFIGURACIONES:Este estudio de cohorte retrospectivo se realizó entre enero de 2010 y diciembre de 2015. Los pacientes se dividieron entre grupos de adenocarcinoma mucinoso y adenocarcinoma no mucinoso. La supervivencia libre de enfermedad y la supervivencia global se evaluaron utilizando emparejamiento por puntuación de propensión.PACIENTES:En general, 2,532 pacientes que se sometieron a cirugía radical para etapa II y III de cáncer de colon se incluyeron en el estudio.PRINCIPALES MEDIDAS DE RESULTADO:Las principales medidas de resultado fueron la supervivencia libre de enfermedad y la supervivencia general.RESULTADOS:La mediana de duración del seguimiento fue de 86 meses. La supervivencia libre de enfermedad y la supervivencia global fueron significativamente menores en el grupo de adenocarcinoma mucinoso que en el grupo de adenocarcinoma no mucinoso. En el análisis de subgrupos, no hubo diferencias significativas en la supervivencia libre de enfermedad y la supervivencia global entre los pacientes con o sin adenocarcinoma mucinoso con cáncer de cólon etapa II. En el cáncer de colon etapa III, la supervivencia libre de enfermedad y la supervivencia global fueron significativamente más bajas en pacientes con adenocarcinoma mucinoso que en aquellos sin adenocarcinoma mucinoso. El análisis multivariable mostró que el adenocarcinoma mucinoso era un factor de mal pronóstico para la supervivencia libre de enfermedad y la supervivencia global.LIMITACIONES:Las limitaciones del estudio incluyen aquellas que están inherentemente asociadas con estudios retrospectivos de un solo centro.CONCLUSIONES:El adenocarcinoma mucinoso es un factor de mal pronóstico en el cáncer de colon etapa III pero no en etapa II. Por lo tanto, el adenocarcinoma mucinoso podría no considerarse un factor de riesgo independiente que requiera quimioterapia para obtener resultados oncológicos favorables. Sin embargo, para el cáncer de colon etapa III, los pacientes con adenocarcinoma mucinoso requieren observación cercana. (Traducción-Dr. Aurian Garcia Gonzalez ).

Management of 80 sinonasal undifferentiated carcinomas. Retrospective multicentre study of the French Network of Rare Head and Neck Cancers (REFCOR)

ObjectivesSinonasal undifferentiated carcinoma (SNUC) is a rare and aggressive disease requiring multimodal treatment, and multiple new entities once included in the spectrum of SNUC, such as SWI/SNF-deficient carcinomas, are emerging. We aimed to provide new data regarding the role of chemotherapy and surgery and the prognostic factors of disease-free survival. MethodsThis study was based on data from the REFCOR database and included patients with SNUC treated with curative intent from 2007 to 2021 across 22 centres in France. ResultsA total of 80 patients were included in the analysis. Among the entire cohort, the 5-year disease-free survival (DFS) and overall survival (OS) rates were 58% and 63%, respectively. Of 100% of the patients treated with irradiation, 29% underwent surgery, 56% neoadjuvant chemotherapy (82% had either a partial or a complete response) and 76% chemoradiotherapy. No treatment modality was associated with a better OS or DFS, including surgery (p = 0.34). There was a trend for a better DFS for the patients treated with chemotherapy (neoadjuvant or concomitant, p = 0.062). Overall survival at 3 years was 58% for SWI/SNF deficient group and 86% for non deficient group (p = 0.14). The locoregional relapse rate without distant metastases was 21% in the exclusive radiotherapy group and 26% in the surgery group. Grade 3 or higher toxicities concerned 9%, 32% and 29% of patients for surgery, radiotherapy and chemotherapy respectively. ConclusionIn the management of localised SNUC among all patients treated with irradiation, surgery yielded no benefit, whereas the addition of chemotherapy tended to improve disease-free survival.

Prognostic Significance of Volumetric Parameters Based on FDG PET/CT in Patients with Lung Adenocarcinoma Undergoing Curative Surgery.

FDG PET/CT is a robust imaging modality to diagnose and stratify prognoses for non-small cell lung carcinoma. However, the role of FDG PET/CT in operable lung adenocarcinoma patients has not been previously investigated in a large cohort with varying pathological stages. The prognostic value of volumetric parameters based on FDG PET/CT was investigated in patients with stage I-III lung adenocarcinoma receiving curative surgery. This retrospective study included 432 patients with lung adenocarcinoma undergoing preoperative FDG PET/CT between January 2016 and December 2017. Clinicopathologic variables, conventional image parameters, such as the maximum standardized uptake value (SUVmax) and mean SUV (SUVmean) of the primary tumor, and volumetric parameters, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG), were included in Cox regression analysis. Subgroup analysis was conducted to compare hazard ratios (HRs) based on MTV in each pathological stage. A new staging system including volumetric parameters was suggested. A total of 432 patients (median age: 62 years; interquartile range: 56-70 years; 225 males) were evaluated. Sex, age, presence of EGFR mutation, pathological stage, MTV, and TLG of the primary tumor were selected as statistically significant prognostic factors for overall survival irrespective of other variables (OS; p < 0.05 for all). Pathological stage, MTV, and TLG of the primary tumor were selected as statistically significant prognostic factors for disease-free survival irrespective of other variables (p < 0.05 for all). The suggested new staging system including MTV as an additional criterion showed better discrimination and prediction for OS than the conventional pathological staging system despite statistical insignificance (concordance index: 0.698 vs. 0.673). The volumetric parameters of the primary tumor based on preoperative FDG PET/CT were independent prognostic factors in addition to pathological stage in patients with operable lung adenocarcinoma. The suggested new staging system considering MTV predicted the prognoses better than the conventional pathological staging system.

Development and validation of a prognostic prediction model for patients with stage Ⅰ to Ⅲ colon cancer incorporating high-risk pathological features

Objective: To examine a predictive model that incorporating high risk pathological factors for the prognosis of stage Ⅰ to Ⅲ colon cancer. Methods: This study retrospectively collected clinicopathological information and survival outcomes of stage Ⅰ~Ⅲ colon cancer patients who underwent curative surgery in 7 tertiary hospitals in China from January 1, 2016 to December 31, 2017. A total of 1 650 patients were enrolled, aged (M(IQR)) 62 (18) years (range: 14 to 100). There were 963 males and 687 females. The median follow-up period was 51 months. The Cox proportional hazardous regression model was utilized to select high-risk pathological factors, establish the nomogram and scoring system. The Bootstrap resampling method was utilized for internal validation of the model, the concordance index (C-index) was used to assess discrimination and calibration curves were presented to assess model calibration. The Kaplan-Meier method was used to plot survival curves after risk grouping, and Cox regression was used to compare disease-free survival between subgroups. Results: Age (HR=1.020, 95%CI: 1.008 to 1.033, P=0.001), T stage (T3:HR=1.995,95%CI:1.062 to 3.750,P=0.032;T4:HR=4.196, 95%CI: 2.188 to 8.045, P<0.01), N stage (N1: HR=1.834, 95%CI: 1.307 to 2.574, P<0.01; N2: HR=3.970, 95%CI: 2.724 to 5.787, P<0.01) and number of lymph nodes examined (≥36: HR=0.438, 95%CI: 0.242 to 0.790, P=0.006) were independently associated with disease-free survival. The C-index of the scoring model (model 1) based on age, T stage, N stage, and dichotomous variables of the lymph nodes examined (<12 and ≥12) was 0.723, and the C-index of the scoring model (model 2) based on age, T stage, N stage, and multi-categorical variables of the lymph nodes examined (<12, 12 to <24, 24 to <36, and ≥36) was 0.726. A scoring system was established based on age, T stage, N stage, and multi-categorical variables of lymph nodes examined, the 3-year DFS of the low-risk (≤1), middle-risk (2 to 4) and high-risk (≥5) group were 96.3% (n=711), 89.0% (n=626) and 71.4% (n=313), respectively. Statistically significant difference was observed among groups (P<0.01). Conclusions: The number of lymph nodes examined was an independent prognostic factor for disease-free survival after curative surgery in patients with stage Ⅰ to Ⅲ colon cancer. Incorporating the number of lymph nodes examined as a multi-categorical variable into the T and N staging system could improve prognostic predictive validity.

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.

Transferrin Receptor is Associated with Sensitivity to Ferroptosis Inducers in Hepatocellular Carcinoma.

Transferrin receptor (TFR), a membrane protein that has a critical role in the transport of iron into cells, is known to be a ferroptosis-related marker. Although TFR is reported to be abundantly expressed in tumor cells, its relationship with ferroptosis inducers in hepatocellular carcinoma (HCC) remains unclear. The authors performed immunohistochemical staining of TFR and divided 350 HCC patients into two groups according to its expression. They analyzed the association between TFR expression and prognosis or clinicopathologic factors. In addition, the regulation of malignant activity and its effect on the efficacy of ferroptosis inducers were investigated in vitro. For this study, 350 patients were divided into TFR-positive (n =180, 51.4%) and TFR-negative (n = 170, 48.6%) groups. The TFR-positive group had more hepatitis B surface antigen (HBs-Ag) (p = 0.0230), higher α-fetoprotein (AFP) levels (p = 0.0023), higher des-gamma-carboxyprothrombin (DCP) levels (p = 0.0327), a larger tumor size (p = 0.0090), greater proportions of Barcelona Clinic Liver Cancer (BCLC) stage B or C (p = 0.0005), poor differentiation (p < 0.0001), and microscopic intrahepatic metastasis (p = 0.0066). In the multivariate analyses, TFR expression was an independent prognostic factor in disease-free survival (p = 0.0315). In vitro, TFRC knockdown decreased cell motility. In addition, TFRC knockdown abolished artesunate (AS)-, lenvatinib-, and sorafenib-induced ferroptosis in HCC cell lines. The study demonstrated that simultaneous treatment of AS with multi-kinase inhibitor augmented the ferroptosis-inducing effects of AS in HCC cell lines. TFR expression is a poor prognostic factor in HCC, but its expression increases sensitivity to ferroptosis-inducing agents.

Prognostic significance of trophoblastic cell surface antigen 2 expression and pathologic parameters in patients with ampullary adenocarcinoma

Trophoblastic cell surface antigen 2 (TROP2) has been reported to be upregulated in several types of carcinomas and is associated with aggressive behavior and poor survival. However, TROP2 expression and its clinical significance in ampullary adenocarcinoma (AA) have not been investigated. We examined TROP2 expression by immunohistochemistry in 112 patients with AAs. The associations of TROP2 expression with clinicopathologic characteristics were evaluated by Chi-squared analyses or Fischer' exact tests. The associations of TROP2 expression and pathologic parameters with survival were evaluated by Kaplan-Meier method, univariate and multivariate cox regression analyses. Eighty-six AAs (76.8%) were positive for TROP2, which showed a membranous and cytoplasmic staining. TROP2 expression was associated with higher frequency (P=0.04) and higher number (P=0.03) of lymph node metastasis, higher pN stage (P=0.03), less frequent adenoma (P=0.04), and higher frequency of recurrence/metastasis (P=0.004). TROP2 expression was associated with shorter disease-free survival (P=0.02) and overall survival (P=0.03). TROP2 expression was an independent prognostic factor for disease-free survival (P=0.04). We demonstrated TROP2 was expressed in 76.8% of AAs. TROP2 expression was associated with higher frequency and high number of lymph node metastasis and higher pN stage. More importantly, TROP2 expression was associated with higher frequency of recurrence/metastasis, shorter disease-free and overall survival and was an independent prognostic factor for disease-free survival. Our results suggest that TROP2 may be used both as a prognostic marker and therapeutic target for patients with AAs.

MFNG is an independent prognostic marker for osteosarcoma

BackgroundOsteosarcoma (OS) has been the most common malignancy of the bone in children and adolescents, and the unsatisfactory prognosis of OS sufferers has long been a hard nut. Here, we delved into the markers with a prognostic value for predicting the prognosis of OS patients.MethodsThe messenger RNA (mRNA) sequencing data and clinical data of OS were retrieved from a Gene Expression Omnibus (GEO) dataset (GSE39058). Next, prognosis-related genes (PRGs) were filtered with the aid of Kaplan–Meier (K-M) curves and Cox regression analysis (CRA). Later, Gene Ontology (GO) biological process analysis was used in verifying the function of different genes. CCK-8 and cell apoptosis assay were performed to evaluate the function of MFNG in U2OS cells.ResultsAmong the obtained genes, Manic Fringe (MFNG) had the closest relevance to prognosis and clinical traits, thus becoming the research object herein. In light of the expression level of MFNG, patients fell into high- and low-MFNG groups. Patients with elevated MFNG expression had a worse prognosis, according to the survival analysis. It was unveiled by the univariate and multivariate analyses that MFNG expression was an independent adverse prognostic factor for disease-free survival in OS patients (p = 0.006). Meanwhile, MFNG expression was linked to gender and tumor recurrence, and it was higher in patients with OS recurrence. Moreover, overexpression of MFNG promoted the cell proliferation and inhibited the cell apoptosis of U2OS cells.ConclusionsThe expression level of MFNG negatively correlated with OS progression, and as an independent adverse prognostic factor for disease-free survival in OS patients. Moreover, MFNG regulated the cell proliferation and apoptosis of OS cells.

A real-world study of adjuvant anti-PD -1 immunotherapy on stage III melanoma with BRAF, NRAS, and KIT mutations.

Melanoma frequently harbors BRAF, NRAS, or KIT mutations which influence both tumor development and treatment strategies. For example, it is still controversial whether adjuvant anti-PD-1 monotherapy or BRAF/MEK inhibitors may better improve the survival for resected BRAF-mutant melanoma. Furthermore, outcomes for melanoma with NRAS and KIT mutation receiving adjuvant immunotherapy remain unclear. One hundred seventy-four stage III melanoma patients who underwent radical surgery in Fudan University Shanghai Cancer Center (FUSCC) during January 2017 to December 2021 were included in this real-world study. Patients were followed up until death or May 30th, 2022. Pearson's chi-squared test or Fisher's exact test was performed for univariable analysis of the different category groups. Log-rank analysis was used to identify the prognostic factors for disease-free survival (DFS). There were 41 (23.6%) patients with BRAF mutation, 31 (17.8%) with NRAS mutation, 17 (9.8%) with KIT mutation, and 85 (48.9%) wild-type patients without either genomic alteration of those three genes. Most ( n = 118, 67.8%) of them were acral melanoma, while 45 (25.9%) were cutaneous subtype, and 11 were (6.3%) primary unknown. Among them, 115 (66.1%) patients received pembrolizumab or toripalimab monotherapy as adjuvant therapy; 22 (12.6%) patients received high-dose interferon (IFN), and 37 (21.3%) patients were just for observation. There was no statistical difference in clinicopathologic factors between anti-PD-1 group and IFN/OBS group. Of all the enrolled patients, anti-PD-1 group had a better DFS than IFN/OBS group ( p = 0.039). In anti-PD-1 group, patients with BRAF or NRAS mutations had poorer DFS than wild-type group. No survival difference was found among patients harboring different gene mutations in IFN/OBS group. In wild-type patients, anti-PD-1 group had a better DFS than IFN/OBS group ( p = 0.003), while no survival benefits were found for patients with BRAF, NRAS, or KIT mutations. Although anti-PD-1 adjuvant therapy provides a better DFS in the general population and in wild-type patients, patients with BRAF, KIT or, especially, NRAS mutation may not benefit further from immunotherapy than conventional IFN treatment or observation.

Clinicopathologic Features of Noninvasive Inverted Urothelial Papillary Tumor.

Clinicopathologic features and recurrence rates of inverted noninvasive urothelial papillary tumors have been poorly characterized to date with few larger studies evaluating long-term outcomes. The spectrum of histomorphology, clinical features, and prognosis of inverted lesions of the urinary bladder are retrospectively reviewed. Archived paraffin-embedded urothelial tumor samples from patients diagnosed with inverted urothelial papillary lesions between January 2005 and June 2020 were collated. A matched control population of patients with exophytic papillary lesions of the urothelium diagnosed during the same time period was randomly selected. The conventional clinicopathologic features of inverted urothelial papillary tumor were evaluated retrospectively and patient demographics, tumor characteristics, recurrence, and survival information were recorded. Lower recurrence rates were observed for inverted papillary urothelial neoplasm of low malignant potential (IPUNLMP) relative to papillary urothelial neoplasms of low malignant potential and for low-grade papillary urothelial carcinoma with an inverted growth pattern (LG-PUCI) relative to low-grade papillary urothelial carcinomas. No recurrence was found among the inverted urothelial papilloma cases. The 2- and 5-year disease-free survival rates were 100.0% and 85.2% for IPUNLMP patients; 94.4% and 80.4% for papillary urothelial neoplasms of low malignant potential; 89.5% and 82.0% for LG-PUCI; 73.7% and 54.6% for low-grade papillary urothelial carcinoma; 40.0% and 20.0% for high-grade papillary urothelial carcinoma with an inverted growth pattern patients and 26.7% and 26.7% for high-grade papillary urothelial carcinoma. Multivariate Cox regression analysis of IPUNLMP and LG-PUCI/high-grade papillary urothelial carcinoma with an inverted growth pattern indicated that tumor number (hazard ratio=4.356; 95% CI: 1.145-16.570; P =0.031) was a powerful prognostic factor for disease-free survival. Noninvasive, papillary urothelial lesions of the bladder tend to have lower recurrence and a better outcome if an inverted growth pattern is shown.

Outcomes of surveillance versus adjuvant treatment for patients with stage-I seminoma: a single-center experience.

Testicular germ cell tumors (seminoma/non-seminoma) are the most common carcinomas in young males, comprising approximately 1% of all carcinomas. In stage-I disease, orchiectomy can cure approximately 85% of patients. Post-surgical options are adjuvant therapy and active surveillance. Our study examined the effects of management options on stage-I seminoma patients followed in our center. We evaluated the patients with stage-I testicular seminoma who underwent radical orchiectomy and followed up in the oncology center between 2001 and 2022. The outcomes of management options, survivals were retrospectively analyzed. The prognostic significance of risk factors for relapse on survival was evaluated. Of the 140 patients with stage-I seminoma, 49 (35%) were treated with adjuvant therapy, and 91 (65%) underwent surveillance. The median follow-up duration was 37months. During the follow-up period, nine patients in the active surveillance group and four in the adjuvant therapy group had a recurrence. There was no statistically significant difference between the two groups (p = 0.67). In the surveillance group, the univariate and multivariate analyzes identified the presence of lymphovascular invasion (p = 0.005, HR: 0.13) as significant prognostic factor for disease-free survival (DFS). In the surveillance cohort, the 5-year DFS rate was 60% for patients with lymphovascular invasion and 93% for those without. There was statistical significance between the two groups (p = 0.003). Our study shows that adjuvant therapy does not significantly improve DFS compared to surveillance in patients. In addition, it has been shown that lymphovascular invasion is an important prognostic indicator for DFS in determining the treatment strategy.

Prognostic significance of uncertain resection for metastasis in the highest mediastinal lymph node after surgery for clinical N0 non-small cell lung cancer.

The International Association for the Study of Lung Cancer defined types of surgical resection and considered the positivity of the highest mediastinal lymph node resected a parameter of "uncertain resection" (R-u). We investigated the metastases in the highest mediastinal lymph node, defined as the lowest numerically numbered station among those resected. We aimed to evaluate the prognostic value of R-u compared with R0. We selected 550 patients with non-small cell lung cancer at clinical Stage I, IIA, IIB (T3N0M0), or IIIA (T4N0M0) undergoing lobectomy and systematic lymphadenectomy between 2015 and 2020. The R-u group included patients with positive highest mediastinal resected lymph node. In the groups of patients with mediastinal lymph node metastasis, we defined 31 as R-u (45.6%, 31/68). The incidence of metastases in the highest lymph node was related to the pN2 subgroups (p < 0.001) and the type of lymphadenectomy performed (p < 0.001). The survival analysis compared R0 and R-u: 3-year disease-free survival was 69.0% and 20.0%, respectively, and 3-year overall survival was 78.0% and 40.0%, respectively. The recurrence rate was 29.7% in R0 and 71.0% in R-u (p-value < 0.001), and the mortality rate was 18.9% and 51.6%, respectively (p-value < 0.001). R-u variable showed a tendency to be a significant prognostic factor for disease-free survival and overall survival (hazard ratio: 4.6 and 4.5, respectively, p-value < 0.001). The presence of metastasis in the highest mediastinal lymph node removed seems to be an independent prognostic factor for mortality and recurrence. The finding of these metastases represents the margin of cancer dissemination at the time of surgery, so it could imply metastasis into the N3 node or distant metastasis.

Prognostic factors of long-term outcomes after primary chemo-radiotherapy in non-metastatic anal squamous cell carcinoma: An international bicentric cohort.

e15501 Background: Anal squamous cell carcinoma (ASCC) is a rare malignancy with a rising incidence associated with Human papillomavirus (HPV) infection. Locally-advanced disease is associated with a 30% rate of treatment failure after standard chemoradiotherapy (CRT). We aimed to elucidate prognostic factors for ASCC after curative CRT. Methods: A retrospective multicenter study of 176 consecutive patients with ASCC having completed CRT treated between 2010 and 2017 at 2 centers. Complete response (CR), disease-free survival (DFS) and overall survival (OS) were analyzed by Kaplan–Meier estimates with log-rank tests. The hierarchical clustering on principal components (HCPC) method was employed in an unsupervised and multivariate approach. Results: CR rate was 68% and was predictive of DFS (p &lt; 0.0001) and OS (p &lt; 0.0001), where non-CR cases were associated shorter DFS (HR = 16.5, 95% CI 8.19-33.21) and OS (HR = 8.42, 95% CI 3.77–18.81) in univariate analysis. Median follow-up was 38 months, with 3-year DFS of 71%. Prognostic factors for DFS were cT1-T2 (p = 0.0001), N0 (p = 0.03), HIV-positive (p = 0.04), HIV-HPV coinfection (p = 0.02), and well-differentiated tumors (p = 0.03). Three-year OS was 81.6%. Female sex (p = 0.05), cT1-T2 (p = 0.019), and well-differentiated tumors (p = 0.003) were associated with better OS. This unsupervised analysis demonstrates clear segregation, identifying that poor prognosis clusters associated with shorter DFS (HR = 1.66, 95% CI = 1.21–2.27, p = 0.0012) were enriched with locally-advanced disease, anal canal location, HPV-HIV coinfection, and non-CR. Conclusions: In conclusion, our results reinforce the prognostic value of T stage, N stage, sex, differentiation status, tumor location, and HIV-HPV coinfection in ASCC after CRT.

Matrix Metalloproteinase 9 Induced in Esophageal Squamous Cell Carcinoma Cells via Close Contact with Tumor-Associated Macrophages Contributes to Cancer Progression and Poor Prognosis.

Tumor-associated macrophages (TAMs) contribute to disease progression in various cancers, including esophageal squamous cell carcinoma (ESCC). We have previously used an indirect co-culture system between ESCC cell lines and macrophages to analyze their interactions. Recently, we established a direct co-culture system to closely simulate actual ESCC cell-TAM contact. We found that matrix metalloproteinase 9 (MMP9) was induced in ESCC cells by direct co-culture with TAMs, not by indirect co-culture. MMP9 was associated with ESCC cell migration and invasion, and its expression was controlled by the Stat3 signaling pathway in vitro. Immunohistochemical analyses revealed that MMP9 expression in cancer cells at the invasive front ("cancer cell MMP9") was related to high infiltration of CD204 positive M2-like TAMs (p < 0.001) and was associated with worse overall and disease-free survival of patients (p = 0.036 and p = 0.038, respectively). Furthermore, cancer cell MMP9 was an independent prognostic factor for disease-free survival. Notably, MMP9 expression in cancer stroma was not associated with any clinicopathological factors or patient prognoses. Our results suggest that close interaction with TAMs infiltrating in cancer stroma or cancer nests induces MMP9 expression in ESCC cells, equipping them with more malignant features.

Preoperative HALP score is a prognostic factor for intrahepatic cholangiocarcinoma patients undergoing curative hepatic resection: association with sarcopenia and immune microenvironment.

The hemoglobin-albumin-lymphocyte-platelet (HALP) score is a combination index that assesses nutritional status and systemic inflammatory response and is reported to predict prognosis in several cancer types. However, researches about the usefulness of the HALP score in intrahepatic cholangiocarcinoma (ICC) are limited. This was a single-center, retrospective study of 95 patients who underwent surgical resection for ICC between 1998 and 2018. We divided patients into two groups by calculating the cutoff value of the HALP score and examined clinicopathological characteristics, prognosis, and sarcopenia. Tumor-infiltrating lymphocytes (TILs), CD8 + TILs, and FOXP3 + TILs were evaluated by immunohistochemical staining of resected tumors. Of 95 patients, 22 were HALP-low. The HALP-low group had significantly lower hemoglobin (p = 0.0007), lower albumin (p = 0.0013), higher platelet counts (p < 0.0001), fewer lymphocytes (p < 0.0001), higher CA19-9 levels (p = 0.0431), and more lymph node metastasis (p = 0.0013). Multivariate analysis revealed that the independent prognostic factors for disease-free survival were maximum tumor size (≥ 5.0cm) (p = 0.0033), microvascular invasion (p = 0.0108), and HALP score (≤ 25.2) (p = 0.0349), and that factors for overall survival were lymph node metastasis (p = 0.0020) and HALP score (≤ 25.2) (p = 0.0014). The HALP-low group contained significantly more patients with sarcopenia (p = 0.0015). Immunohistochemistry showed that counts of CD8 + TILs were significantly lower in the HALP-low group (p = 0.0075). We demonstrated that low HALP score is an independent prognostic factor for ICC patients undergoing curative hepatic resection and is associated with sarcopenia and the immune microenvironment.

Clinicopathologic Features and Prognosis of Melanoma in Northeast China: A Region-Based Cohort Study of 229 Consecutive Cases

Melanoma has been reported in many parts of East Asia. However, there are no reports on the epidemiology of melanoma in Northeast China. In this study, we collected demographic, clinicopathologic, and treatment data of patients with melanoma treated at the First Hospital of Jilin University (Changchun, China). A total of 229 consecutive nonselective cases were analyzed for the incidence and clinicopathologic characteristics of melanoma. The median overall survival was 53.5 months. The 1-year, 3-year, and 5-year survival rates were 86.3, 66.4, and 44.8%, respectively. The median disease-free survival was 33.1 months, and the 1-year, 3-year, and 5-year disease-free survival rates were 75.0, 48.5, and 35.8%, respectively. Multivariate analysis showed that disease stage, Eastern Cooperative Oncology Group score, and lactic dehydrogenase were independent prognostic factors of overall survival. Pathologic subtype and stage were independent prognostic factors of disease-free survival. Furthermore, vascular invasion was a prognostic factor for overall survival in acral melanoma and a prognostic factor for disease-free survival in cutaneous melanoma. Compared with the Caucasian population, the population of Northeast China showed significant differences in disease location, pathologic subtype, gene status, and survival prognosis. In summary, our study showed that vascular invasion might be a prognostic factor in patients with acral and cutaneous melanoma.

Short-term efficacy analysis and comprehensive evaluation of laparoscopy for patients with rectal cancer-a prospective multi-center study

ObjectiveTo compare the short-term efficacy indicators of laparoscopic technique and open surgery in patients with rectal cancer surgery, and to further evaluate the safety and efficacy of laparoscopic rectal cancer surgery.MethodsThis study adopted a prospective multicenter, open-label, non-randomized concurrent control method to analyze patients who received rectal cancer surgery from 10 colorectal tumor centers across the country from January 2017 to December 2018. The two groups of patients received laparoscopic-assisted surgery and conventional open surgery respectively. All surgeons were selected according to relevant standards and participated in the two groups of operations at the same time. Comprehensive evaluation and analysis of the operation and postoperative recovery, postoperative pathological results, survival information, postoperative related functional scores and other indicators.ResultsIn the open surgery group, the proportion of tumors with a maximum diameter of more than 5 cm was higher (χ2 = 0.089, P = 0.018), and the proportion of T4 was higher (χ2 = 0.478, P < 0.001). In the laparoscopic group, the proportion of more than 12 harvested lymph nodes was higher (χ2 = 0.248, P < 0.001). There were no significant differences in the length of postoperative hospital stay, intraoperative blood loss, time to first flatus after operation, time to first out of bed, time to first liquid diet, and preservation rate of anal sphincter between the two groups, but in the laparoscopic surgery group the operation time was shorter (t = 6.750, P < 0.001) and postoperative pain was less (t = 0.896, 0.63, 0.964, and 0.989 on postoperative days 1, 2, and 3, respectively, all P < 0.001). The incidence of grade 2–4 adverse complication in the two groups was 12.5% and 14.6%, respectively, with no statistical difference (χ2 = 0.061, P = 0.105), but the incidence of incision infection was lower in the laparoscopy group (χ2 = 0.19, P < 0.001). There was no significant difference in 3-year disease-free survival between the two groups (HR = 1.089, 95% CI = 0.962–1.232, P = 0.170). Multivariate analysis suggested that intraoperative blood loss, T stage, N stage, nerve invasion, and postoperative sepsis were independent prognostic factors for disease-free survival. Wexner score, IPSS score and LARS score were not statistically different between the two groups.ConclusionThe pathological results and short-term outcomes of laparoscopic surgery for rectal cancer are comparable to those of conventional open surgery, and laparoscopic surgery is safe and feasible for rectal cancer patients.

The significance of peri-neural invasion in patients with gallbladder carcinoma after curative surgery: a 10year experience in China.

The significance of peri-neural invasion (PNI) in patients with gallbladder carcinoma (GBC) after curative surgery remains unknown. Current study was performed to evaluate the significance of PNI in resected GBC patients in terms of tumor-related biological features and long-term survival. Patients with GBC between September 2010 and September 2020 were reviewed and analyzed. SPSS 25.0 software were used for statistical analysis. A total of 324 resected GBC patients were identified (No. PNI: 64). An elevated preoperative Ca19.9 level (P = 0.001), obstructive jaundice (P = 0.001), liver invasion (P < 0.0001), lymph-vascular invasion (P < 0.0001), lymph-node metastasis (P < 0.0001), and poor or moderate differentiation status (P = 0.036) were more frequently detected in patients with PNI. Major hepatectomy (P = 0.019), bile duct resection (P < 0.0001), combined multi-visceral resections (P = 0.001), and combined major vascular resections and reconstructions (P = 0.002) were also more frequently detected. However, a significantly lower R0 rate (P < 0.0001) was acquired in patients with PNI. Patients with PNI were generally more advanced disease and shared a much worse prognosis even after matching. PNI was an independent prognostic factor of disease-free survival as well as an independent predictor of early recurrence. Postoperative adjuvant chemotherapy has brought an obvious survival benefit in resected GBC patients with PNI. PNI could be regarded as an indicator of worse prognosis and could serve as an independent predictor of early recurrence. Postoperative adjuvant chemotherapy was correlated with an improved survival for resected GBC patients with PNI. Upcoming multicenter studies covering various races are warranted for further validation.