Risk Factor For Recurrence-free Survival Research Articles

Recurrence risk analysis for stage II and III colorectal cancer, and the implications of diabetes mellitus as a risk factor for the recurrence of stage III colorectal cancer.

The present study investigated the risk factors for recurrence in patients with stage II-III colorectal cancer (CRC) who underwent colorectal surgery. Data from 232 patients with stage II and III CRC who underwent primary tumor resection were retrospectively analyzed. Univariate and multivariate analyses were performed to determine the risk factors for recurrence. The overall recurrence rate was 21.6% (n=50/232). Univariate Cox regression analysis identified diabetes mellitus (DM) (P=0.032) as a risk factor for recurrence. In addition, multivariate Cox regression analysis showed that DM was an independent risk factor for recurrence-free survival (RFS) (hazard ratio 2.40, P=0.016). The RFS curve obtained using the Kaplan-Meier method indicated that in patients with stage III colon cancer, the non-DM group demonstrated a significantly longer RFS than the DM group (P=0.012). In conclusion, the present study demonstrated that DM may be an independent risk factor for recurrence in patients undergoing curative resection for stage III CRC. Consequently, better postoperative therapy and careful monitoring might be required, especially in patients with stage III CRC and preoperative DM.

Model for end-stage liver disease-dependent prognostic capacity of platelet-to-lymphocyte ratio following liver transplantation for hepatocellular carcinoma

BackgroundTo improve liver organ allocation, the model for end-stage liver disease (MELD) score was adopted in candidates reflecting the severity of liver disease and the physical condition of patients. Inflammatory markers are prognostic factors for various cancers and play prognostic roles in patients after liver transplantation (LT) for hepatocellular carcinoma (HCC). Researchers focused more on pre-LT inflammatory markers, while the role of dynamic change of these inflammatory markers is still unknown. The purpose of this study was to estimate the prognostic value of pre-LT and post-LT inflammatory markers. Material and methodsWe collected the pre-LT complete blood count and the post-LT result with highest count of white blood cells within 48 h. Platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio and systemic immune-inflammation index were calculated, and their prognostic roles were analyzed for their MELD scores. ResultsThis retrospective two-center cohort study enrolled 290 patients after LT for HCC. Multivariate analysis identified pre-LT PLR as independent risk factor for recurrence-free survival (RFS) [HR (95%CI): 1.002 (1.000–1.003), p = 0.023]. A high pre-LT PLR or post-LT PLR were associated with poorer RFS (p < 0.001 and p = 0.004, respectively). Based on the MELD scores, the pre-LT PLR value was able to predict the RFS in high MELD group (p < 0.001) but had no predictive power in low MELD group (p = 0.076). On the contrary, the post-LT PLR value was better to predict the overall RFS value in low MELD group (p = 0.007) but could not predict the overall RFS value in high MELD group (p = 0.136). ConclusionsBoth pre-LT PLR and post-LT PLR demonstrated prognostic value in patients following LT for HCC. Monitoring PLR values based on the MELD score can improve the predictive prognosis and more effectively guide the individual decisions for the postoperative intervention.

Treatment and prognosis study of spontaneous rupture hemorrhage in hepatocellular carcinoma: Recommendations for adding the A1 stage to the BCLC staging system.

The Barcelona Clinic Liver Cancer (BCLC) staging system is an internationally recognized clinical staging system for hepatocellular carcinoma (HCC). However, this staging system does not address the staging and surgical treatment strategies for patients with spontaneous rupture hemorrhage in HCC. In this study, we aimed to investigate the prognosis of patients with BCLC stage A undergoing liver resection for HCC with spontaneous rupture hemorrhage and compare it with the prognosis of patients with BCLC stage A undergoing liver resection without rupture. Clinical data of 99 patients with HCC who underwent curative liver resection surgery were rigorously followed up and treated at Shandong Provincial Hospital from January 2013 to January 2023. A retrospective cohort study design was used to determine whether the presence of ruptured HCC (rHCC) is a risk factor for recurrence and survival after curative liver resection for HCC. Prognostic comparisons were made between patients with ruptured and non-ruptured BCLC stage A HCC (rHCC and nrHCC, respectively) who underwent curative liver resection. rHCC (hazard ratio [HR] = 2.974, [p] = 0.016) and tumor diameter greater than 5 cm (HR = 2.819, p = 0.022) were identified as independent risk factors for overall survival (OS) after curative resection of BCLC stage A HCC. The postoperative OS of the spontaneous rupture in the HCC group (Group I) was shorter than that in the BCLC stage A group (Group II) (p = 0.008). Tumor invasion without penetration of the capsule was determined to be an independent risk factor for recurrence-free survival (RFS) after liver resection for HCC (HR = 2.584, p = 0.002). HCC with concurrent spontaneous rupture hemorrhage is an independent risk factor for postoperative OS after liver resection. TheBCLC stage A1 should be added to complement the current BCLC staging system to provide further guidance for the treatment of patients with spontaneous rupture of HCC.

Prognostic implication of consolidation-to-tumor ratio in early lung adenocarcinoma: a retrospective cross-sectional study.

The threshold value of consolidation-to-tumor ratio (CTR) for distinguishing between ground-glass opacity (GGO)-predominant and solid-predominant ground-glass nodules (GGNs) needs to be clarified, as the lack of clarity has caused the prognostic implications to remain ambiguous. This study aimed to determine the threshold value of CTR for distinguishing between GGO-predominant GGNs and solid-predominant GGNs and elucidate the prognostic implications of the solid-predominant GGNs categorized by CTR on c-stage IA lung adenocarcinoma. Between January 2016 and October 2018, 764 c-stage IA lung adenocarcinoma cases were assembled from the First Affiliated Hospital of Chongqing Medical University. Of the 764 lesions, 515 (67.4%) were nodules with a GGO component, and 249 (32.6%) were solid nodules (SNs) on thin-section computed tomography (CT). We evaluated the correlation of the 3-dimensional (3D) consolidation component volume ratio with CTR based on the coefficient of determination, r. After receiver operating characteristic (ROC) analysis of 515 GGNs, we defined the nodule with CTR >0.750 as solid-predominant GGN and the nodule with CTR ≤0.750 as GGO-predominant GGN. Subsequently, the prognosis of 439 patients who had follow-up registration was evaluated. Survival curves were calculated using the Kaplan-Meier method, and the log-rank test was employed to compare survival rates among different groups. Cox proportional hazard regression models were applied to evaluate the independent risk factors for recurrence-free survival (RFS). Among 764 patients, 515 (67.4%) were nodules with a GGO component, and 249 (32.6%) were SNs on thin-section CT. For 515 GGNs, the 3D consolidation component volume ratio correlated well with CTR (r=0.888). CTR tended to be slightly larger than the 3D consolidation component volume ratio. A 3D consolidation component volume ratio >50% was best predicted by CTR >0.750, followed by CTR >0.549. CTR >0.750 and CTR >0.549 predicted 3D consolidation component volume ratio >50% with 85% and 99.2% sensitivity and 91.6% and 57.2% specificity, respectively. The 5-year RFS and overall survival (OS) of patients with 0.750< CTR <1 were worse than those of patients with 0≤ CTR ≤0.750 (P<0.001 and P<0.001, respectively) but better than those of patients with CTR =1 (P=0.002 and P=0.03, respectively). Carcinoembryonic antigen (CEA) >2.1 [hazard ratio (HR) =12.516, 95% confidence interval (CI): 1.729-90.598], CTR >0.750 (HR =13.934, 95% CI: 3.341-58.123), larger consolidation component size with diameter more than 20 mm (HR =1.855, 95% CI: 1.242-2.770), poorly differentiated (HR =1.622, 95% CI: 1.056-2.491), lymph node metastasis (HR =2.473, 95% CI: 1.601-3.821), and sublobar resection (HR =2.596, 95% CI: 1.701-3.962) could predict the poor prognosis. Patients with 0≤ CTR ≤0.750 receiving sublobar resection had prognoses comparable to those receiving lobar resection, whether the tumor size ≤2 cm or consolidation component size ≤3 cm. Lobar resection was superior to sublobar resection for non-small cell lung cancer (NSCLC) ≤2 cm with CTR >0.750. Compared to CTR =0.5, the 2-dimensional (2D) CTR =0.750 found using the 3D consolidation component volume ratio as the gold standard better differentiated between solid-predominant GGNs and GGO-predominant GGNs. CTR >0.750 was an independent risk factor associated with the poor prognosis of patients with c-stage IA lung adenocarcinoma. Sublobar resection should be cautiously adopted in GGNs with 0.750< CTR ≤1.

Development and comprehensive validation of a predictive prognosis model for very early HCC recurrence within one year after curative resection: a multicenter cohort study.

The high incidence of early recurrence after liver resection for hepatocellular carcinoma (HCC) is the main obstacle in achieving good long-term survival outcomes. The aim of the present study is to develop a prognostic model in predicting the risk of very early (1-year) recurrence. Consecutive patients who underwent liver resection for HCC with curative intent at multi-centers in China were enrolled in this study. The VERM-pre (the Preoperative Very Early Recurrence Model of HCC) with good performance was derived and validated by internal and external cohorts retrospectively and by another two-center cohort prospectively. 7401 patients were enrolled and divided randomly into 3 cohorts. Eight variables (tumor diameter, tumor number, macrovascular invasion, satellite nodule, alpha-fetoprotein, level of HBV-DNA, γ-GT and prothrombin time) were identified as independent risk factors for recurrence-free survival on uni- and multi-variate analyses. The VERM-pre model was developed which showed a high capacity of discrimination (C-index: 0.722; AUROC at 1 year: 0.722)) and was validated comprehensively by the internal, external and prospective cohorts, retrospectively. Calibration plots showed satisfactory fitting of probability of early HCC recurrence in the cohorts. Three risk strata were derived to have significantly different recurrence free survival rates (low-risk: 80.4%-85.4%; intermediate-risk: 59.7%-64.8%; high-risk: 32.6%-42.6%). In the prospective validation cohort, the swimming plot illustrated consistent outcomes with the beginning predictive score. The VERM-pre model accurately predicted the 1-year recurrence rates of HCC after liver resection with curative intent. The model was retrospectively and prospectively validated and then developed as the online tool.

Clinical outcome of non-curative endoscopic submucosal dissection for early gastric cancer.

Early gastric cancer (EGC) is defined as cancer cells confined to the mucosal or submucosal layer, irrespective of size or presence of lymph node metastasis. The recent EGC endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) guidelines (2021 Japan Gastroenterological Endoscopy Society (JGES) guidelines, 2nd edition) revised the concept from "endoscopic curative/non-curative resection" (NCR) to "endoscopic curability (eCura)". Under this, eCuraA and eCuraB signify curative resections (CRs), while eCuraC (including eCuraC-1 and eCura-C2) indicate NCRs. This study retrospectively analyzes clinical and pathological data from EGC patients who underwent endoscopic resection, assessing the long-term clinical outcomes in a substantial cohort after undergoing NCR. We retrospectively analyzed clinical and pathological data from 443 EGC patients, encompassing 478 lesions, who received endoscopic treatment. The long-term clinical outcomes of patients who underwent NCR were statistically evaluated. Characteristics of the NCR group were compared with those of the surgical group, employing single- and multi-factor logistic regression analyses to identify risk factors that necessitate further surgical intervention. Prognostically, the Kaplan-Meier method and Log-Rank test determined the impact of risk factors on recurrence-free survival post-surgery in NCR patients. Differences were assessed using a method incorporating statistically significant differences in the multi-factor Cox regression analysis, evaluating the hazard ratio (HR) for disease recurrence following NCR. In this study, 443 EGC cases were pathologically diagnosed, comprising a total of 478 lesions. Of these, 127 cases underwent non-curative endoscopic resection, resulting in a NCR rate of 24.4%. Long-term follow-up was achieved for 117 (92.12%) patients. The metastasis/recurrence rate at 6 months stood at 23.1%. Multivariate Cox regression analysis identified lesion size ≥2.0 and <3 cm [P=0.02, HR =0.12, 95% confidence interval (CI): 0.02-0.67], presence of ulceration (P=0.03, HR =5.48, 95% CI: 1.23-24.33), lymphatic invasion (P=0.05, HR =17.51, 95% CI: 1.07-286.23), positive vertical margins (P=0.09, HR =3.77, 95% CI: 0.81-17.53), and flat macroscopic morphology (P=0.048, HR =4.8, 95% CI: 1.01-22.73) as independent risk factors for recurrence-free survival post non-curative endoscopic resection in EGC patients. The recurrence/metastasis rate in patients who underwent NCR is notably higher compared to the control group. Significant prognostic risk factors include tumor size ≥2.0 and <3 cm, positive vertical margins, lymphatic invasion, and flat type (one of pathological gross classification). Patients in the eCuraC-2 category of NCR should consider further surgical intervention. The necessity for additional surgical intervention in these patients warrants further investigation.

Component Patterns and Survival Outcomes in Patients with Mixed Malignant Ovarian Germ Cell Tumors: A Retrospective Cohort Study

AimsTo evaluate the component patterns and risk stratification in patients with mixed malignant ovarian germ cell tumors (mMOGCT). MethodsA retrospective study of 70 mMOGCT patients treated in our hospital between 2000 and 2022 was conducted. The recurrence-free survival (RFS), disease-specific survival (DSS), and risk stratification systems based on scoring the identified prognostic factors were assessed. ResultsYolk sac tumor component was the most common type (80%), followed by dysgerminoma (50%), immature teratoma (40%), embryonic carcinoma (27.1%), and chorionic carcinoma (15.7%). The 5-year RFS and DSS rates were 77.9% and 87.9%, respectively. International federation of gynecology and obstetrics (FIGO) stage III-IV (RR 3.253, P = 0.029) and normalization of tumor marker (TM) ≤ 3 cycles of chemotherapy (RR 6.249, P = 0.017) were risk factors for RFS and DSS, respectively. Significant DSS (RR 8.268, P = 0.006) was also noted between patients who had normalized TM ≤ 4 and ≥5 cycles of chemotherapy. FIGO stages I–II and stages III–IV were scored as 0 and 2, respectively. AFP normalization ≤3, 4, and ≥5 cycles of chemotherapy were scored as 0, 1, and 4, respectively. A total score of 0, 1–2, and ≥3 stratified patients into low-risk (43 patients), intermediate-risk (13 patients), and high-risk groups (14 patients), respectively. Patients in three risk stratifications manifested significant differences in DSS (P = 0.010) but not in RFS (P > 0.05). ConclusionDistinct different component patterns existed among mMOGCT patients, and predicting survival outcomes in a universal model was challenging.

Adipose Tissue Quantification Improves the Prognostic Value of GLIM Criteria in Advanced Gastric Cancer Patients.

The present study investigated whether the risk of recurrence after curative surgery could be further stratified by combining the Global Leadership Initiative on Malnutrition (GLIM) criteria and changes in subcutaneous (SAT) and visceral (VAT) adipose tissue mass after surgery in patients with advanced gastric cancer (AGC). This study retrospectively analyzed 302 patients with AGC who underwent curative surgery. Based on the GLIM criteria, patients were classified into malnourished and non-malnourished groups. The cross-sectional areas of SAT and VAT were measured from preoperative and 6-month post-operative computed tomography (CT) images. Multivariate survival analyses demonstrated that GLIM-defined malnutrition (p = 0.008) and loss of VAT after surgery (p = 0.008) were independent risk factors for recurrence-free survival (RFS). Evaluation of the prognostic value of combining the two independent predictors showed that malnourished patients with a marked loss of VAT had the worst 5-year RFS rate of 35.2% (p < 0.001). Preoperative GLIM-defined malnutrition and a loss of VAT during the first 6 months after surgery were independent predictors for RFS in patients with AGC. Changes in the VAT area after surgery could further enhance the prognostic value of the GLIM criteria for predicting the risk of gastric cancer recurrence.

Oncological outcomes and hospitalization cost of hyperthermic intraperitoneal chemotherapy (HIPEC) open and closed abdomen techniques: Results from two French expert centers

BackgroundHyperthermic intraperitoneal chemotherapy (HIPEC) associated with CC0 excision is performed using either an open (OPEN_HIPEC) or closed abdominal technique (CLOSED_HIPEC). However, little data is available on the costs of this treatment, as there is no code for HIPEC in the French Classification of Medical Acts. Oncological outcomes and the mean cost of hospitalization were compared. MethodsBetween 2017-2021, 144 patients with peritoneal carcinomatosis (all etiologies) were included (OPEN_HIPEC, n = 70; CLOSED_HIPEC, n = 74) in this retrospective two-center study. Morbi-mortality, overall survival (OS), recurrence-free-survival (RFS) and mean cost of hospitalization were compared. ResultsThe median OS and RFS were 71.3 months [63–71.5] and 26.8 months [20–35.3] respectively, and were similar for both techniques; and after stratification by histology. Multivariate analysis adjusted on PCI score of OS identified mitomycin as a protective factor (HR = 0.31 [0.10–0.90], p = 0.032) and ASA score>2 as a risk factor of RFS (HR = 2.21 [1.28–3.83], p = 0.004). Complication rates at day 30 were similar between OPEN and CLOSED_HIPEC, 31 (44.3 %) vs 42 (56.8 %); p = 0.135. OPEN_HIPEC had more severe complications (11(35.5 %) vs 6(14.3 %); p = 0.034). The mean cost of hospitalization was estimated as €15,627 for OPEN_HIPEC and €14,211 for CLOSED_HIPEC for a mean length-of-stay of 12.7 and 16.7 days respectively. The mean amount received by the hospital per hospitalization was estimated at €16,399 and €15,536 respectively. ConclusionsOS and RFS were similar for open and closed HIPEC. Severe complications at day 30 were more frequent in OPEN_HIPEC group. The amount received by hospital for both HIPEC techniques is sufficient.

Feasibility of laparoscopic versus open pancreatoduodenectomy following neoadjuvant chemotherapy for borderline resectable pancreatic cancer: a retrospective cohort study

BackgroundThere is no evidence supporting the feasibility of laparoscopic pancreaticoduodenectomy (LPD) compared to open pancreatoduodenectomy (OPD) following neoadjuvant chemotherapy (NACT) for pancreatic ductal adenocarcinoma (PDAC).MethodsThe clinical data of consecutive patients with borderline resectable PDAC who received NACT and underwent either LPD or OPD between January 2020 and December 2022 at Fudan University Shanghai Cancer Center was prospectively collected and retrospectively analyzed.ResultsThe analysis included 57 patients in the OPD group and 20 in the LPD group. Following NACT, the LPD group exhibited a higher median CA19-9 decrease rate compared to the OPD group (85.3% vs. 66.9%, P = 0.042). Furthermore, 3 anatomically borderline PDACs in the LPD group and 5 in the OPD group were downstaged into resectable status (30.0% vs. 12.3%, P = 0.069). According to RECIST criteria, 51 (66.2%) patients in the entire cohort were evaluated as having stable disease. The median operation time for the LPD group was longer than the OPD group (419 vs. 325 min, P < 0.001), while the venous resection rate was 35.0% vs. 43.9%, respectively (P = 0.489). There was no difference in the number of retrieved lymph nodes, with a median number of 18.5 in the LPD group and 22 in the OPD group, and the R1 margin rate (15.0% vs. 12.3%) was also comparable. The incidence of Clavien-Dindo complications (35.0% vs. 66.7%, P = 0.018) was lower in the LPD group compared to the OPD group. Multivariable regression analysis revealed that a tumor diameter > 3 cm before NACT (HR 2.185) and poor tumor differentiation (HR 1.805) were independent risk factors for recurrence-free survival, and a decrease rate of CA19-9 > 70% (OR 0.309) was a protective factor for early tumor recurrence and overall survival.ConclusionsLPD for PDAC following NACT is feasible and oncologically equivalent to OPD. Effective control of CA19-9 levels is beneficial in reducing early tumor recurrence and improving overall survival.

Geriatric Nutritional Risk Index Is an Independent Prognostic Factor for Patients With Esophageal Cancer Who Receive Curative Treatment.

The perioperative nutritional status has recently been reported to influence the prognosis of various types of cancer. We investigated the relationship between the Geriatric Nutritional Risk Index (GNRI) and overall survival (OS) and recurrence-free survival (RFS) in patients with esophageal cancer who received radical and adjuvant therapy. Patients who underwent radical resection for esophageal cancer at our hospital (n=187) were included. Background characteristics, surgical factors, and OS were examined retrospectively. The GNRI was calculated using preoperative values, with GNRI <98 classified as low-GNRI. Seventy-five and 112 patients were classified into the GNRI-low and -high groups, respectively. The 3- and 5-year OS rates were 75.7% and 66.7%, respectively, in the GNRI-high group and 43.2% and 36.7% in the GNRI-low group; the difference was statistically significant (p<0.001). In the univariate and multivariate analyses, low-GNRI was selected as a risk factor for OS. The hazard ratio for low-GNRI was 2.184 (95% confidence interval=1.361-3.508, p=0.001). The 5-year RFS rate in the high- and low-GNRI groups was 54.6% and 25.0%, respectively (p=0.001). In the univariate and multivariate analyses, low-GNRI was a risk factor for RFS. The hazard ratio for low-GNRI was 1.704 (95%CI=1.121-2.590, p=0.013). Regarding the type of recurrence, lymph node recurrence was significantly more common in the low-GNRI group (p=0.008). Low-GNRI was an independent risk factor for OS and RFS after radical resection of esophageal cancer. The preoperative GNRI may be a useful prognostic factor after esophageal cancer surgery.

HER-2 Expression in Colorectal Cancer and Its Correlation with Immune Cell Infiltration.

This study aimed to investigate the effect of increased HER-2 expression on tumor-infiltrating lymphocytes (TILs) and determine its impact on the prognosis of colorectal cancer (CRC) patients; Methods: HER-2, CD4, CD8, CD19, LY6G, CD56, CD68, CD11b, and EpCam expression in CRC tissues and adjacent paracancerous tissues were assessed using multiplex fluorescence immunohistochemical staining. The correlation between HER-2 expression and the number of TILs in CRC tissues was analyzed. Kaplan-Meier and Cox proportional hazards models were used to analyze survival outcomes; Results: The expression of HER-2 in tumor tissues was higher than that in paracancerous tissues (1.31 ± 0.45 vs. 0.86 ± 0.20, p < 0.05). Additionally, there was an increase in the numbers of CD4+, CD8+, CD19+, and CD68+ cells in CRC tissues (14.11 ± 1.10 vs. 3.40 ± 0.18, p < 0.005; 0.16 ± 0.12 vs. 0.04 ± 0.04, p < 0.005; 0.71 ± 0.46 vs. 0.25 ± 0.13, p < 0.0005; 0.27 ± 0.24 vs. 0.03 ± 0.11, p < 0.05). An increase in HER-2 expression was positively correlated with an increase in CD4, CD8, and CD19 (p < 0.0001). In HER-2-positive CRC tissues, CD68 expression was increased (0.80 ± 0.55 vs. 0.25 ± 0.22, p < 0.05). In HER-2-upregulated CRC tissues, CD4, CD8, CD19, CD68, CD11b, Ly6G, and CD56 expressions were elevated (0.70 ± 0.37 vs. 0.32 ± 0.17, p = 0.03; 0.22 ± 0.13 vs. 0.09 ± 0.06, p = 0.03; 0.31 ± 0.19 vs. 0.12 ± 0.08, p = 0.02; 1.05 ± 0.62 vs. 0.43 ± 0.21, p < 0.01; 1.34 ± 0.81 vs. 0.53 ± 0.23, p < 0.01; 0.50 ± 0.31 vs. 0.19 ± 0.10, p < 0.01; 1.26 ± 0.74 vs. 0.52 ± 0.24, p < 0.01). Furthermore, increased HER-2 expression was an independent risk factor for recurrence-free survival (RFS) in patients (p < 0.01, HR = 3.421); Conclusions: The increased expression of HER-2 and its relationship with immune cells will provide new insights for immunotherapy in CRC patients.

Conditional recurrence analysis of intrahepatic cholangiocarcinoma: Changes in recurrence rate and survival after recurrence resection by disease-free interval.

The prognosis of patients with resected intrahepatic cholangiocarcinoma (ICC) is still unsatisfactory, with a high recurrence rate. We aimed to evaluate risks of recurrence changing over time and the survival benefit of resection for recurrent ICC. This study included patients who underwent hepatectomy for ICC during 1995-2020. Risk factors for recurrence-free survival (RFS) in patients undergoing initial resection and overall survival (OS) in patients who developed recurrence after initial resection were analyzed. Conditional cumulative incidence of recurrence was assessed. A total of 169 patients were included in the study and 114 patients (67.5%) developed recurrence. Cumulative analyses showed that the 5-year recurrence rate was 69.3% at the time of initial resection but decreased to 24.8% in patients free from recurrence at 2years after initial resection and 2.6% in patients free from recurrence at 4years. Re-resection was carried out in 26 (22.8%) of 114 patients who developed recurrence. Multivariable Cox proportional hazards model analysis indicated re-resection (hazard ratio [HR] 0.19; 95% confidence interval [CI] 0.11-0.40, p<0.001), microvascular invasion (MVI) (HR 2.39; 95% CI 1.05-5.40, p=0.037), and disease-free interval (months) (HR 0.97; 95% CI 0.95-1.00, p=0.067) were significantly associated with longer OS after recurrence. Although the rate of recurrence remains high, conditional cumulative recurrence rate analysis showed that the rate of recurrence decreased by disease-free interval. Resection of recurrent ICC was associated with improved OS, particularly among patients with longer disease-free interval and absence of MVI after initial hepatectomy.

Analysis of clinicopathological features of 18 cases of hepatic angiosarcoma

Objective: To investigate the clinicopathological features, treatment, and prognosis of hepatic angiosarcoma. Methods: Clinicopathological data and prognostic conditions of 18 cases with hepatic angiosarcoma were collected retrospectively. The recurrence-free survival rate and overall survival rate were calculated by the Kaplan-Meier method. A Cox regression analysis was used to explore the survival-related risk factors. Results: There were 12 male and 6 female patients, with an average age of 57 (37 ~ 70) years. The tumor's average diameter was 8.40 (2.00 ~ 18.00) cm. Seven cases had multiple tumors, while two cases had large vessel tumor thrombuses. Microscopically, the tumor tissues were irregularly anastomosed, with vascular lacunar or solid bundle-like weaving, and the tissue morphology mimicked capillary hemangioma, cavernous hemangioma, or angioepithelioma, while tumor cells were spindle-shaped or epithelioid, lined with hobnails in the lumen, or formed papillary structures in the lumen. The proportion of highly, moderately, and poorly differentiated tumors was 4:8:6, with six cases having clear tumor boundaries, eight having microvascular tumor thrombi, and sixteen having blood lake formation. Different levels of expression of CD31, CD34, erythroblast transformation-specific related genes, and Fli-1 markers were demonstrated in all of the cases. Four cases had a P53 mutation, and six cases had Ki-67 > 10%. During the follow-up period of 0.23-114.20 months, the five-year recurrence-free survival rate and overall survival rate were 16.7% and 37.2%, respectively. Cox regression multivariate analysis showed that preoperative symptoms and multiple tumors were significant risk factors for recurrence-free survival, while preoperative symptoms and Ki-67 > 10% were significant risk factors for overall survival. Conclusion: Hepatic angiosarcoma is a rare hepatic mesenchymal tumor with high malignancy and a poor prognosis. Pathological morphology and immunohistochemical marker combinations are needed for a definite diagnosis. However, the complexity of angiosarcomas' histological and cytological conformations and the overlap of pathological features with benign vascular tumors, sarcomas, and carcinomas pose difficulties in the differential diagnosis. Thus, the only effective ways to prolong survival are early detection and radical surgical resection.

Outcomes of Long-Term Follow-up of Patients Receiving Antithyroid Medication for Hyperthyroidism due to Graves' Disease

Background: Thyrotropin (also known as thyroid stimulating hormone (TSH)) receptors antibodies (TRAb) activate thyroid follicular cells in the autoimmune condition known as Graves' hyperthyroidism, which causes thyrotoxicosis and swelling of the thyroid gland. Objective: Using a thorough retrospective cohort design, this research assessed the effectiveness of antithyroid drugs (ATDs) and risk variables linked to the recurrence of Graves' hyperthyroidism. Methods: With enough follow-up data, we evaluated 2100 individuals who had just received a Graves' hyperthyroidism diagnosis. Evaluation of the treatment results of the subjects and risk factors for recurrence-free survival, particularly alterations in thyrotropin receptors antibodies. Results: The participants' average age was 44.8 years, and 64% of them were females. After using ATD for a median of 22.9 months (interquartile range (IQR) 16.9-34.4), 1450 participants were given the option to discontinue the medication. Initial remission ratio was 56.6%. 95.24% of participants completed the second round of ATD therapy after the initial recurrence and the remission ratio was 56.6%. 7.14% of participants required surgery, and 10.9% received radioactive iodine treatment, throughout the course of a median follow-up duration of 67 months. About 29.7% of patients were still receiving ATD medication for chronic lower-dose maintained or recurring illness. Male gender, being younger (&lt;45 years old), and fluctuating or smoldering of TRAb levels were all distinct risk indicators for the first recurrence following ATD therapy. Conclusions: ATD therapy is a viable choice for both chronic condition and the first therapy of Graves' hyperthyroidism. The individual risk indicators of recurring must be determined to identify the effective therapeutic duration for ATD therapy.

Clinical characteristics and survival outcomes in patients with primary ovarian carcinoid: A historical cohort study.

Primary ovarian carcinoids are extremely rare ovarian tumors, and there is limited data available on their clinical characteristics and survival outcomes. We conducted a historical cohort study of 56 patients to investigate their clinical characteristics. The overall survival, disease-specific survival, recurrence-free survival, and potential prognostic factors of these patients were also evaluated. The median age of these patients was 42.0 years (range: 20-71). The average mass and carcinoid size was 7.3 and 0.4 cm, respectively. Elevated tumor marker levels and ascites were observed in 15 and 10 patients, respectively. In 98.2% of the patients, tumors were confined to the ovary, while only one had metastatic disease. Surgery was the mainstay therapy: 37.5% of the patients underwent unilateral salpingo-oophorectomy, 25.0% underwent hysterectomy with bilateral salpingo-oophorectomy, 21.4% underwent ovarian cystectomy, 10.7% underwent comprehensive staging surgery, and 5.4% underwent bilateral salpingo-oophorectomy. Appendectomy and lymphadenectomy were performed in eight and five patients, respectively, but none showed tumor involvement. Chemotherapy was the only adjuvant treatment utilized, and was administered in four patients. Pathological analysis showed that strumal carcinoid was the most predominant subtype, occurring in 66.1% of the patients. The Ki-67 index was reported in 39 patients, 30 of which had an index of no more than 3%, with a maximum of only 5%. Only one relapse occurred after the initial treatment, and that patient experienced recurrences on two occasions, maintaining stable disease after surgery and octreotide therapy. After a median follow-up of 3.6 years, 96.4% of the patients achieved no evidence of disease, while 3.6% were alive with the disease. The 5-year recurrence-free survival rate was 97.9% and no death occurred. No risk factors for recurrence-free survival, overall survival, or disease-specific survival were identified. The Ki-67 indices were extremely low and prognoses were excellent in patients with primary ovarian carcinoids. Conservative surgery, especially unilateral salpingo-oophorectomy, is preferred. Individualized adjuvant therapy may be considered for patients with metastatic diseases.

Bioinformatics analysis and experimental validation of a novel autophagy-related signature relevant to immune infiltration for recurrence prediction after curative hepatectomy

Hepatocellular carcinoma (HCC) remains imposing an enormous economic and healthcare burden worldwide. In this present study, we constructed and validated a novel autophagy-related gene signature to predict the recurrence of HCC patients. A total of 29 autophagy-related differentially expressed genes were identified. A five-gene signature (CLN3, HGF, TRIM22, SNRPD1, and SNRPE) was constructed for HCC recurrence prediction. Patients in high-risk groups exhibited a significantly poor prognosis compared with low-risk patients both in the training set (GSE14520 dataset) and the validation set (TCGA and GSE76427 dataset). Multivariate cox regression analysis demonstrated that the 5-gene signature was an independent risk factor for recurrence-free survival (RFS) in HCC patients. The nomograms incorporating 5-gene signature and clinical prognostic risk factors were able to effectively predict RFS. KEGG and GSEA analysis revealed that the high-risk group was enriched with multiple oncology characteristics and invasive-related pathways. Besides, the high-risk group had a higher level of immune cells and higher levels of immune checkpoint-related gene expression in the tumor microenvironment, suggesting that they might be more likely to benefit from immunotherapy. Finally, the immunohistochemistry and cell experiments confirmed the role of SNRPE, the most significant gene in the gene signature. SNRPE was significantly overexpressed in HCC. After SNRPE knockdown, the proliferation, migration and invasion ability of the HepG2 cell line were significantly inhibited. Our study established a novel five-gene signature and nomogram to predict RFS of HCC, which may help in clinical decision-making for individual treatment.

The Prognostic Value of Preoperative Serum Markers and Risk Classification in Patients with Hepatocellular Carcinoma.

Complex hepatocellular carcinoma (HCC) prognostic biomarkers have been reported in various studies. We aimed to establish biomarkers that could predict prognosis, and formulate a simple classification using non-invasive preoperative blood test data. We retrospectively identified 305 patients for a discovery cohort who had undergone HCC-related hepatectomy at four Japanese university hospitals between January 1, 2011 and December 31, 2013. Preoperative blood test parameter optimal cut-off values were determined using receiver operating characteristic curve analysis. Cox uni- and multivariate analyses were used to determine independent prognostic factors. Risk classifications were established using classification and regression tree (CART) analysis. Validation was performed with 267 patients from three other hospitals. In multivariate analysis, α-fetoprotein (AFP, p < 0.001), protein induced by vitamin K absence or antagonist-II (PIVKA-II, p = 0.006), and C-reactive protein (CRP, p < 0.001) were independent prognostic factors for overall survival (OS). AFP (p = 0.007), total bilirubin (p = 0.001), and CRP (p = 0.003) were independent recurrent risk factors for recurrence-free survival (RFS). CART analysis results formed OS (CRP, AFP, and albumin) and RFS (PIVKA-II, CRP, and total bilirubin) decision trees, based on machine learning using preoperative serum markers, with three risk classifications. Five-year OS (low risk, 80.0%; moderate risk, 56.3%; high risk, 25.2%; p < 0.001) and RFS (low risk, 43.4%; moderate risk, 30.8%; high risk, 16.6%; p < 0.001) risks differed significantly. These classifications also stratified OS and RFS risk in the validation cohort. Three simple risk classifications using preoperative non-invasive prognostic factors could predict prognosis.

The prognostic effect of immunohistochemical staining rates in patients with non-muscle-invasive bladder cancer.

Despite the follow-up protocols developed in non-muscle-invasive bladder cancer patients, progression and recurrence could not be prevented. We aimed to investigate whether proteins such as OCT-4, CD47, p53, Ki-67, and Survivin, which increase in bladder cancer cells, can be used as prognostic markers for patients with non-muscle-invasive bladder cancer. The study included a total of 89 patients with newly diagnosed non-muscle-invasive bladder cancer between January 2015 and December 2020. Levels of OCT-4, CD47, p53, Kİ-67, and Survivin proteins in cancer cells were determined with a semi-quantitative immunohistochemical experiment. Pathological data and survival rates were compared according to the staining rates. Data obtained in the study were analyzed statistically with SPSS 22.0 (SPSS, Chicago, IL, USA). The mean age of the patients was 64.25 ± 9.91 years, and the median follow-up period was 55 months. Recurrence rate was determined to be 36% (n = 32), and the rate of progression at 40.4% (n = 36). The staining rates were stronger for each marker in the progression group and advanced-stage tumors (p < 0.001). The findings of the multivariate analysis carried out as part of the study showed that older age and higher tumor stage were independent risk factors for recurrence-free survival (HR = 1.048 and 7.074, respectively; P = 0.02). Also, higher tumor stages, diameters, and grades were associated with reduced progression-free survival (HR = 0.105, 0.395, 0.225, respectively; P < 0.05). Although immunohistochemical staining rates are promising, it is more appropriate to use tumor characteristics when assessing survival rate in patients with non-muscle-invasive bladder cancer.

The efficacy of a machine learning algorithm for assessing tumour components as a prognostic marker of surgically resected stage IA lung adenocarcinoma.

The importance of the stromal components in tumour progression has been discussed widely, but their prognostic role in small size tumours with lepidic components is not fully understood. Applying digital tissue image analysis to whole-slide imaging may enhance the accuracy and reproducibility of pathological assessment. This study aimed to evaluate the prognostic value of tumour components of lung adenocarcinoma by measuring the dimensions of the tumour consisting elements separately, using a machine learning algorithm. Between September 2002 and December 2016, 317 patients with surgically resected, pathological stage IA adenocarcinoma with lepidic components were analysed. We assessed the whole tumour area, including the lepidic components, and measured the epithelium, collagen, elastin areas and alveolar air space. We analysed the prognostic impact of each tumour component. The dimensions of the epithelium and collagen areas were independent significant risk factors for recurrence-free survival (hazard ratio, 8.38; 95% confidence interval, 1.14-61.88; P=0.037, and hazard ratio, 2.58; 95% confidence interval, 1.14-5.83; P=0.022, respectively). According to the subgroup analysis when combining the epithelium and collagen areas as risk factors, patients with tumours consisting of both large epithelium and collagen areas showed significantly poor prognoses (P=0.002). We assessed tumour components using a machine learning algorithm to stratify the post-operative prognosis of surgically resected stage IA adenocarcinomas. This method might guide the selection of patients with a high risk of recurrence.