Median Recurrence-free Survival Time Research Articles

Tissue inhibitor of metalloproteinase-3 expression affects clinicopathological features and prognosis of aflatoxin B1-related hepatocellular carcinoma.

The dysregulation of tissue inhibitor of metalloproteinase-3 (TIMP3) was positively correlated with the progression of hepatocellular carcinoma (HCC). However, it is not clear whether TIMP3 expression is associated with the clinicopathological features and prognosis of aflatoxin B1 (AFB1)-related HCC (AHCC). To assess the effects of TIMP3 expression on the clinicopathological features and prognosis of AHCC. A retrospective study, including 182 patients with AHCC, was conducted to explore the link between TIMP3 expression in cancerous tissues and the clinicopathological characteristics and prognosis of AHCC. TIMP3 expression was detected by immunohistochemistry and its effects on the clinicopathological features and prognosis of AHCC were evaluated by Kaplan-Meier survival analysis and Cox regression survival analysis. Odds ratio, hazard ratio (HR), median overall survival time (MST), median tumor recurrence-free survival time (MRT), and corresponding 95% confidential interval (CI) was calculated to evaluate the potential of TIMP3 expression in predicting AHCC prognosis. Kaplan-Meier survival analysis showed that compared with high TIMP3 expression, low TIMP3 expression in tumor tissues significantly decreased the MST (36.00 mo vs 18.00 mo) and MRT (32.00 mo vs 16 mo) of patients with AHCC. Multivariate Cox regression survival analysis further proved that decreased expression of TIMP3 increased the risk of death (HR = 2.85, 95%CI: 2.04-4.00) and tumor recurrence (HR = 2.26, 95%CI: 1.57-3.26). Furthermore, decreased expression of TIMP3 protein in tissues with AHCC was significantly correlated with tumor clinicopathological features, such as tumor size, tumor grade and stage, tumor microvessel density, and tumor blood invasion. Additionally, TIMP3 protein expression was also negatively associated with amount of AFB1-DNA adducts in tumor tissues. These findings indicate that the dysregulation of TIMP3 expression is related to AHCC biological behaviors and affects tumor outcome, suggesting that TIMP3 may act as a prognostic biomarker for AHCC.

Clinical characteristics and predisposing factors of lung metastasis in sacral chordoma: a cross-sectional cohort study of 221 cases.

Limited studies are available on the topic of lung metastasis in sacral chordoma. The primary objective of this study was to investigate the prevalence, characteristics, associated factors, and prognosis of lung metastasis in sacral chordoma. A total of 221 cases with primary sacral chordoma, all of whom underwent surgical resection at our center, were included in this study. Comprehensive demographic information, imaging findings, and oncological evaluations were collected and thoroughly analyzed. The diagnosis of lung metastasis in the majority of cases was established through radiographic examinations. The prevalence of lung metastasis in the cohort was 19.5%, with the lung emerging as the predominant site of distant metastasis. Recurrent chordoma cases exhibited a significantly higher lung metastasis rate in comparison to newly diagnosed chordoma cases (33.33% and 12.76%, p=0.0005). Patients with lung metastasis had a larger tumor size, a higher proportion of previous sacral chordoma surgeries and a greater likelihood of postoperative recurrence. Associated factors of lung metastasis were tumor size, postoperative recurrence and radiotherapy. Patients with lung metastasis exhibited decreased median overall survival (91 vs. 144 months for those without lung metastasis, p<0.05) and recurrence-free survival (27 vs. 68 months, p<0.001) times. Lung is the most common site of distant metastasis in sacral chordoma with an incidence rate nearly 20%. Larger tumor size and postoperative recurrence are risk factors for lung metastasis while radiotherapy is a protective factor. Occurrence of lung metastasis in sacral chordoma is a negative prognostic factor.

Correlation between tumor budding and the long-term follow-up outcomes after endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma.

The effect of tumor budding (TB) on the prognosis of patients with esophageal squamous cell carcinoma (ESCC) after endoscopic submucosal dissection (ESD) remains unclear. We evaluated the long-term outcomes of patients with superficial ESCC after ESD and the risk factors of TB for the long-term prognosis. We conducted a retrospective study in a Chinese hospital. All patients with ESCC treated by ESD and reported TB were included consecutively. Comparative analyses were conducted in three parts: specimen analysis, follow-up analyses of unmatched patients, and propensity score-matched (PSM) patients. Cox proportional hazard regression models were constructed to identify risk factors for overall survival and recurrence-free survival (RFS). A total of 437 patients were enrolled [154TB and 283 no tumor budding (NTB)], and 258 patients (52TB and 206 NTB) were included in the follow-up analysis. Results showed that the invasion depth, differentiation type, and positive vascular invasion (all p < 0.001) of the TB group were significantly different from the NTB group. The all-cause mortality and the median RFS time between the two groups were comparable. RFS rate at 5years were 84.6% and 80.6%, respectively (p = 0.43). Cox analyses identified that having other cancers but not TB, as a risk factor independently associated with overall survival and RFS after ESD. TB tends to be associated with invasion depth, differentiation type, and positive vascular invasion. However, it might not affect the long-term outcomes of patients with superficial ESCC after ESD when other high-risk factors are negative.

Lumbar functional evaluation of pelvic bone sarcomas after surgical resection and spinal pelvic fixation: A clinical study of 304 cases.

We endeavored to introduce a novel scoring system (Lumbar Functional Index, LFI) capable of evaluating lumbar function in pelvic bone sarcoma patients who underwent surgical resection and spinal pelvic fixation, while simultaneously identifying the incidence, outcomes, and risk factors of lumbar function impairment among these populations. A cohort of 304 primary bone sarcoma patients were recruited. The LFI was created based on the Oswestry Dysfunction Index (ODI) and Japanese Orthopaedic Association (JOA) scores. Lumbar function impairment was defined as LFI score ≥ 18 points, which was identified as high LFI. Demographic data, clinical characteristics, and oncological outcomes were analyzed. The cohort included chondrosarcoma (39.8%), osteosarcoma (29.9%), Ewing sarcoma (8.6%), bone-derived undifferentiated pleomorphic sarcoma (7.2%), giant cell tumor of bone (7.2%), chordoma (2.3%), and other bone sarcomas (5.0%). The LFI score exhibited significant negative correlation with common scoring systems of bone sarcoma. The incidence of high LFI was 23.0%. Patients with high LFI demonstrated a higher prevalence of type I + II + III + IV pelvic tumor, more sacrificed nerve roots and bilateral lumbar spine fixation during surgery, while lower percentage of R0 resection and local control of pelvic tumor. Decreased median overall survival (30 vs. 52 months, p < 0.001) and recurrence-free survival (14 vs. 24 months, p < 0.001) time were observed in these patients. Type I + II + III + IV pelvic tumor and sacrificed nerve roots≥2 were identified as risk factors for high LFI, while R0 resection and local control were identified as protective factors. The LFI scoring system exhibited a significant negative correlation to current scoring systems. High LFI patients had worse prognosis and distinct characteristics. The risk factors of high LFI included type I + II + III + IV pelvic tumor and sacrificed nerve roots≥2, and the protective factors included R0 resection and local control.

The Effect of Renin-Angiotensin System Inhibitors in Patients Undergoing Pancreatic Cancer Resection.

The local renin-angiotensin system promotes angiogenesis and proliferation via vascular endothelial growth factor or epidermal growth factor receptor expression. In this study, we aimed to evaluate the impact of angiotensin system inhibitors (ASIs) on long-term outcomes in patients undergoing surgical resection of pancreatic ductal adenocarcinoma (PDAC). A single institutional retrospective analysis was performed using the medical records of patients who underwent pancreatic resection with curative intent for PDAC between January 2005 and December 2018. Patient characteristics and surgical outcomes were compared between patients taking ASIs and those who are not. A total of 272 patients were included in the study and classified into the ASI group (n = 121) and the non-ASI group (n = 151). The median overall survival times in the ASI group and non-ASI group were 38.0 and 34.0 months ( P = 0.250), and the median recurrence-free survival times were 24.0 and 15.0 months ( P = 0.025), respectively. Multivariate analysis for recurrence-free survival identified the use of ASIs ( P = 0.020), CA19-9 level >500 IU/L ( P = 0.010), positive lymph node metastasis ( P < 0.001), and no adjuvant chemotherapy ( P < 0.001) as independent prognostic factors. The use of ASI may improve long-term outcomes after surgery for PDAC.

Recurrence risk stratification of hepatocellular carcinomas based on immune gene expression and features extracted from pathological images.

Immune-based therapy is a promising type of treatment for hepatocellular carcinoma (HCC) but has only been partially successful due to the high heterogeneity in HCC tumor. The differences in the degree of tumor cell progression and in the activity of tumor immune microenvironment could lead to varied clinical outcome. Accurate subgrouping for recurrence risk is an approach to address the issue of such heterogeneity. It remains under investigation as whether integrating quantitative whole slide image (WSI) features with the expression profile of immune marker genes can improve the risk stratification, and whether clinical outcome prediction can assist in understanding molecular biology that drives the outcome. We included a total of 231 patients from the Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) project. For each patient, we extracted 18 statistical metrics corresponding to a global region of interest and 135 features regarding nucleus shape from WSI. A risk score was developed using these image features with high-dimensional survival modeling. We also introduced into the model the expression profile of 66 representative marker genes relevant to currently available immunotherapies. We stratified all patients into higher and lower-risk subgroup based on the final risk score selected from multiple models generated, and further investigated underlying molecular mechanisms associated with the risk stratification. One WSI feature and three immune marker genes were selected into the final recurrence-free survival (RFS) prediction model following the best integrated modeling framework. The resultant score showed a significantly improved prediction performance on the test dataset (mean time-dependent AUCs = 0.707) as compared to those of other types (e.g: mean time-dependent AUCs of AJCC tumor stage = 0.525) of input data integration. To assess that the risk score could provide a higher-resolution risk stratification, a lower-risk subgroup (or a higher-risk subgroup) was arbitrarily assigned according to score falling below (or above) the median score. The lower risk subgroup had significantly longer median RFS time than that of the higher-risk patients (median RFS = 903 vs. 265 days, log-rank test p-value< 0.0001). Additionally, the higher-risk subgroup, in contrast to the lower-risk patients were characterized with a significant downregulation of immune checkpoint genes, suppressive signal in tumor immune response pathways, and depletion of CD8 T cells. These observations for the higher-risk subgroup suggest that new targets for adoptive or checkpoint-based combined systemic therapies may be useful. We developed a novel prognostic model to predict RFS for HCC patients, using one feature that can be automatically extracted from routine histopathological images, as well as the expression profiles of three immune marker genes. The methodology used in this paper demonstrates the feasibility of developing prognostic models that provide both useful risk stratification along with valuable biological insights into the underlying characteristics of the subgroups identified.

Prognostic significance of positive lymph node regression grade to neoadjuvant chemoradiation for esophageal squamous cell carcinoma.

To assess the relationship between metastatic lymph node (LN) responder status and recurrence-free survival (RFS) in patients undergoing neoadjuvant chemoradiotherapy (NCRT). We retrospectively reviewed 304 patients with local advanced esophageal squamous cell carcinoma received NCRT followed by esophagectomy. For 112 patients with positive node, according to the proportion of residual viable tumor cells area within the whole tumor beds of all metastatic LNs, we classified LN-tumor regression grade (LN-TRG) into four categories: grade 1, 0%; 2, <10%; 3, 10%-50%; 4, >50%. Patients with grade 1-2 LN-TRG of were considered LN responders, and those with grades 3-4, as LN nonresponders. Univariate and multivariate analyses of RFSwere estimated by a Cox regression model, Kaplan-Meier curve, and log-rank test. The median follow-up time of a total of 112 patients was 29.6 months. Fifty-two (46.4%) patients have experienced recurrence. In Cox univariate analysis, differentiation, AJCC stage LN responder status, nerve invasion, and lymphovascular invasion significantly correlated with RFS. Multivariate analysis for RFS revealed that LN responder status and AJCC stage (p < 0.05) were independent prognostic factor. The 3-year RFS rates for patients with LN-TRG of 1-4 grades were 72.7%, 76.5%, 37.4%, and 28.5%, respectively, and the median RFS times were not reach, 43.56, 28.09, and 22.77, respectively. LN responder status is an independent prognostic factor for RFS in esophageal cancer patients who received NCRT.

Salvage treatment for local recurrence after endoscopic resection for superficial nonampullary duodenal epithelial tumors

Background and AimsLocal recurrence is a significant concern in endoscopic resection of superficial nonampullary duodenal tumors (SNADTs). Our objective was to elucidate the clinical outcomes of salvage endoscopic treatment. MethodsThis retrospective study included consecutive patients who underwent endoscopic resection of SNADTs between January 2013 and December 2021. Four hundred thirty-three patients were observed, excluding those with familial adenomatous polyposis and those who did not undergo surveillance endoscopy. Local recurrence was defined as histologically proven adenoma or adenocarcinoma in contact with a prior endoscopic resection scar. The clinicopathological characteristics of patients with local recurrence and outcomes of salvage endoscopic treatment were evaluated. ResultsLocal recurrence occurred in 33 (8%) of the 433 patients after endoscopic resection for SNADT. Multivariate analysis identified older age (≥63 years), larger lesion size (≥13 mm), and piecemeal resection as significant independent predictors of local recurrence. Among the 33 patients with 33 recurrent lesions, 10 lesions (30%) disappeared after forceps biopsy. Three patients (9%) remained untreated. Sixteen lesions (48%) disappeared after one session of salvage endoscopic treatment, and four lesions (12%) disappeared after two sessions of treatment. Among these 24 treatment sessions, underwater endoscopic mucosal resection was performed in 19 sessions. The median post-procedural hospitalization period was four days (interquartile range, 3–4.25 days). Delayed bleeding occurred in three sessions. No recurrences have been detected in the 30 salvaged patients. The median recurrence-free survival time was 24.5 months (interquartile range, 14–48.75 months). ConclusionsLocal recurrence after endoscopic resection of SNADT can be managed endoscopically.

Combination of carbohydrate antigen 19-9 level and tumor size after neoadjuvant chemoradiation therapy may predict early recurrence of resectable pancreatic ductal adenocarcinoma

BackgroundAlthough the overall survival rate of patients with resectable pancreatic cancer has gradually improved, some patients relapse early and have a poor prognosis. This study aimed to identify the preoperative risk factors for early recurrence after neoadjuvant chemoradiotherapy in patients with resectable pancreatic cancer. MethodsThis study analyzed patients who underwent pancreatectomy after receiving neoadjuvant chemoradiotherapy for resectable pancreatic cancer between January 2009 and June 2021 and excluded those with borderline resectable and unresectable pancreatic cancers. Early recurrence was defined as recurrence within 6 months after surgery. ResultsThis study included 203 patients, of whom 22 experienced early recurrence. The median survival time of patients with early recurrence was 18.3 months, which was significantly worse than that of patients with late recurrence (44.0 months, p < 0.001) or no recurrence (not reached, p < 0.001). Logistic regression analysis revealed that a carbohydrate antigen 19-9 level of >100 units/mL and a T status of ≥T2 after neoadjuvant chemoradiotherapy were independent predictive risk factors for early recurrence. The median recurrence-free survival time of patients with two risk factors was 9.7 months and significantly worse than that of those with either risk factors (20.5 months, p = 0.024) and those with no risk factor (26.2 months, p < 0.001). ConclusionsA combination of a high-level carbohydrate antigen 19–9 and a T status of ≥T2 after neoadjuvant chemoradiotherapy are predictors of early recurrence and may be helpful for selecting patients who require a stronger preoperative treatment.

Clinical Characteristics and Predictors of the Recurrence of Organizing Pneumonia Associated With Rheumatoid Arthritis.

To clarify the clinical characteristics of organizing pneumonia (OP) in rheumatoid arthritis (RA; RA-OP) and the association of OP development with RA exacerbation, and to identify OP recurrence predictors. Data from 33 patients with RA-OP admitted to our hospital were retrospectively analyzed (2006-2016). RA onset preceded OP onset in 82% of patients, whereas OP onset preceded (OP-preceding) or co-occurred with RA in 9% of patients each. Median age at first OP onset was 64.0 years, and the period from RA onset to first OP onset was 5.5 years. At OP onset, 42% of events exhibited unilateral involvement and 76% had normal Krebs von den Lungen-6. RA disease control remained optimal in 52% of events and was exacerbated in 18% of events. Ten patients (30%) experienced OP recurrence with an interval of 13.0 months between events, and the first OP recurrence rate was 127/1000 person-years. Compared with nonrecurrent cases (n = 14), recurrent cases (n = 10) showed lower age at first OP onset (59.5 vs 67.1 yrs; P = 0.04) and a shorter period from RA onset to first OP onset (6.4 vs 14.2 yrs; P = 0.047); moreover, these cases included a higher number of OP-preceding patients (30% vs 0%; P = 0.03) and ever smokers (80% vs 36%; P = 0.03). OP-preceding patients showed shorter median recurrence-free survival time (15 vs 136 months; P = 0.01) and higher recurrence risk (hazard ratio 5.45; P = 0.02). RA-OP showed a high recurrence rate and was not associated with RA exacerbation. Four RA-OP recurrence predictors were identified.

Association between autologous transfusion and recurrence-free survival in patients with hepatocellular carcinoma after resection: A prospective nonrandomized controlled trial.

e16206 Background: To investigate whether preoperative stored autologous transfusion has a significant effect on recurrence-free survival of patients with primary hepatocellular carcinoma (HCC). Methods: Recurrence-free survival (RFS), overall survival, and perioperative morbidity were compared among patients with or without autologous transfusion at our medical center between January 2019 and December 2021. Patients who received autologous transfusion were matched based on propensity scores to patients who did not, in order to reduce confounding due to baseline differences. This study was registered on ClinicalTrials.gov (NCT02654028). Results: Of the 618 patients in the analysis, 399 (64.6%) received autologous transfusion and 219 (35.4%) did not receive autologous transfusion. By 30 July 2022, the median RFS time had been achieved. Patients with or without autologous transfusion had similar RFS before (hazard ratio 1.01, 95%CI 0.82-1.24) or after propensity score analysis (hazard ratio 1.04, 95%CI 0.82-1.31). However, the median overall survival was not achieved. Patients with or without autologous transfusion also had similar overall survival before (hazard ratio 1.15, 95%CI 0.84-1.56) or after propensity score analysis (hazard ratio 1.26, 95%CI 0.88-1.79). Moreover, subgroup analyses found that patients with or without autologous transfusion had similar RFS or overall survival among those with early, intermediate, or advanced stage disease. The two groups also had similar rates of perioperative mortality and morbidity. Conclusions: Preoperative stored autotransfusion had no significant effect on survival in patients with HCC who underwent liver resection. Clinical trial information: NCT02654028 .

Clinicopathological features and survival of rare primary pulmonary lymphoepithelial carcinoma: A cohort from a single center.

Primary pulmonary lymphoepithelial carcinoma (PLEC) is a rare subtype of nonsmall cell lung cancer. This study aimed to investigate the clinicopathological and prognostic characteristics of resected primary PLEC. In this retrospective study, 95 consecutive patients with primary PLEC, who received radical surgical resection treatment, were examined from October 2009 to January 2022. The clinicopathological features and their association with survival outcomes were analyzed. Primary PLEC predominated in relatively younger patients and nonsmokers, who lacked driver mutations and were always positive for immunohistochemical markers of the squamous cell lineage. Further, 21.1% of patients had abnormally elevated preoperative serum marker fragments of cytokeratin 19 (Cyfra21-1). The median follow-up time was 43.5 months. The 1-, 3-, and 5-year recurrence-free survival (RFS) rates were 96.5%, 81.8%, and 64.3%, respectively. The median RFS time was not reached. Cox univariate survival analysis showed that patients with positive lymph nodes had significantly worse RFS than those with negative ones (p = 0.017). The patients with open surgery experienced significantly worse RFS than those with video-assisted thoracoscopic surgery (p = 0.038). The multivariate survival analysis confirmed that only lymph node involvement (hazard ratio: 2.769; 95% confidence interval: 1.171-6.548, p = 0.020) was an independent prognostic factor. Primary PLEC is a rare type of lung cancer with a favorable outcome, more common in young and nonsmoking Asian populations. Driver gene mutations are rare. Regional lymph node metastasis is an independent prognostic factor for RFS after radical surgical resection.

Characteristics and outcomes of patients with primary abdominopelvic aggressive angiomyxoma: a retrospective review of 12 consecutive cases from a sarcoma referral center

BackgroundAggressive angiomyxoma (AAM) is a rare mesenchymal tumor that mostly arises from the pelvic and perineal soft tissues. Few studies reported its characteristics and outcomes previously due to its rarity and challenges of treatments. This study aimed to investigate the clinical characteristics as well as surgical and short-term survival outcomes of primary abdominopelvic AAM.MethodsMedical records of patients who were admitted to surgery with pathological confirmation of primary abdominopelvic AAM at Peking University International Hospital from January 2016 through December 2021 were retrospectively retrieved from our retroperitoneal tumor database. Demographics, operative outcomes and pathological findings were collected. Patients received followed-up routinely after the surgery. Survival probabilities were calculated and determined through Kaplan–Meier analysis.ResultsA total of 12 consecutive patients (male/female 4:8) were included in this study. The median age was 45 years old. The clinical presentation varied among individuals, consisting of 2 abdominal discomforts, 4 constipations, 1 lumbago, 1 prolonged menstruation, and 1 buttock swelling. R0/R1 resection was achieved in 100% of patients. Postoperatively, 50% of patients developed various complications including 3 fistulas and 3 wound infections. No operative mortality was observed. Histopathology of all patients was suggestive of AAM. Immunohistochemistry was done with a 91.7% positive rate for estrogen and progesterone receptors. The median recurrence-free survival time was 38 months. There were no cases of deceased or presented with distal metastasis during a median of 42 months’ follow-up.ConclusionsThe clinical manifestations of abdominopelvic AAM are mostly atypical. Surgical resection with curative intents remains the mainstay treatment of this disease, which was strongly suggested in experienced sarcoma centers due to the high probability of severe postoperative complications. In addition, long-term follow-up is necessary due to the high rate of local recurrences.

Impact of previous malignancy at diagnosis on oncological outcomes of upper tract urothelial carcinoma

BackgroundThe evidence of prognostic factors and individualized surveillance strategies for upper tract urothelial carcinoma are still weak.ObjectivesTo evaluate whether the history of previous malignancy (HPM) affects the oncological outcomes of upper tract urothelial carcinoma (UTUC).MethodsThe CROES-UTUC registry is an international, observational, multicenter cohort study on patients diagnosed with UTUC. Patient and disease characteristics from 2380 patients with UTUC were collected. The primary outcome of this study was recurrence-free survival. Kaplan-Meier and multivariate Cox regression analyses were performed by stratifying patients according to their HPM.ResultsA total of 996 patients were included in this study. With a median recurrence-free survival time of 7.2 months and a median follow-up time of 9.2 months, 19.5% of patients had disease recurrence. The recurrence-free survival rate in the HPM group was 75.7%, which was significantly lower than non-HPM group (82.7%, P = 0.012). Kaplan-Meier analyses also showed that HPM could increase the risk of upper tract recurrence (P = 0.048). Furthermore, patients with a history of non-urothelial cancers had a higher risk of intravesical recurrence (P = 0.003), and patients with a history of urothelial cancers had a higher risk of upper tract recurrence (P = 0.015). Upon multivariate Cox regression analysis, the history of non-urothelial cancer was a risk factor for intravesical recurrence (P = 0.004), and the history of urothelial cancer was a risk factor for upper tract recurrence (P = 0.006).ConclusionBoth previous non-urothelial and urothelial malignancy could increase the risk of tumor recurrence. But different cancer types may increase different sites’ risk of tumor recurrence for patients with UTUC. According to present study, more personalized follow-up plans and active treatment strategies should be considered for UTUC patients.

Changes in Modified Raymond–Roy Classification Occlusion Classes and Predictors of Recurrence-Free Survival in Patients with Intracranial Aneurysms after Endovascular Coil Embolization

PurposeTo assess changes in modified Raymond–Roy classification (MRRC) occlusion classes and recurrence rates over time and evaluate recurrence-free survival after coil embolization and its predictors. Materials and MethodsDuring 2007–2016, 201 patients (mean age, 57.1 ± 13.4 years; 75.5% women) with 240 aneurysms treated with coil embolization were enrolled. MRRC Class I (n = 210), Class II (n = 14), Class IIIa (n = 10), and Class IIIb (n =6) closures were assessed. Recurrence was defined as recanalization in MRRC Class I closures or an increase of at least 20% in any of the dimensions of the remnants of the other classes. Recurrence-free survival and its predictors were analyzed using survival analysis. ResultsMost changes in MRRC class occurred in the first year after treatment. MRRC Class I closures had a slightly lower probability of change than that associated with other classes within 1–5 years, whereas Class IIIb closures remained unchanged. Rates of recurrence or regression for all classes were highest within the first year. The median recurrence-free survival times among patients with Class IIIa and Class IIIb closures were 11.56 and 5.55 months, respectively. Significant predictors of recurrence included aneurysm size of 13–24 mm, ruptured or wide-necked aneurysms, and MRRC Class IIIa or IIIb closures. ConclusionsClass changes and recurrence rates for all MRRC classes were highest in the first year. MRRC Class IIIb closures had the highest recurrence rate and the shortest recurrence-free survival. Recurrence risk increased in Classes IIIa and IIIb and with large, ruptured or wide-necked aneurysms.

FDG-PET Predicts Neoadjuvant Therapy Response and Survival in Borderline Resectable/Locally Advanced Pancreatic Adenocarcinoma.

Neoadjuvant therapy (NAT) is used in borderline resectable/locally advanced (BR/LA) pancreatic ductal adenocarcinoma (PDAC). Anatomic imaging (CT/MRI) poorly predicts response, and biochemical (CA 19-9) markers are not useful (nonsecretors/nonelevated) in many patients. Pathologic response highly predicts survival post-NAT, but is only known postoperatively. Because metabolic imaging (FDG-PET) reveals primary tumor viability, this study aimed to evaluate our experience with preoperative FDG-PET in patients with BR/LA PDAC in predicting NAT response and survival. We reviewed all patients with resected BR/LA PDAC who underwent NAT with FDG-PET within 60 days of resection. Pre- and post-NAT metabolic (FDG-PET) and biochemical (CA 19-9) responses were dichotomized in addition to pathologic responses. We compared post-NAT metabolic and biochemical responses as preoperative predictors of pathologic responses and recurrence-free survival (RFS) and overall survival (OS). We identified 202 eligible patients. Post-NAT, 58% of patients had optimization of CA 19-9 levels. Major metabolic and pathologic responses were present in 51% and 38% of patients, respectively. Median RFS and OS times were 21 and 48.7 months, respectively. Metabolic response was superior to biochemical response in predicting pathologic response (area under the curve, 0.86 vs 0.75; P&lt;.001). Metabolic response was the only univariate preoperative predictor of OS (odds ratio, 0.25; 95% CI, 0.13-0.40), and was highly correlated (P=.001) with pathologic response as opposed to biochemical response alone. After multivariate adjustment, metabolic response was the single largest independent preoperative predictor (P&lt;.001) for pathologic response (odds ratio, 43.2; 95% CI, 16.9-153.2), RFS (hazard ratio, 0.37; 95% CI, 0.2-0.6), and OS (hazard ratio, 0.21; 95% CI, 0.1-0.4). Among patients with post-NAT resected BR/LA PDAC, FDG-PET highly predicts pathologic response and survival, superior to biochemical responses alone. Given the poor ability of anatomic imaging or biochemical markers to assess NAT responses in these patients, FDG-PET is a preoperative metric of NAT efficacy, thereby allowing potential therapeutic alterations and surgical treatment decisions. We suggest that FDG-PET should be an adjunct and recommended modality during the NAT phase of care for these patients.

Expression characteristics and diagnostic value of angiogenic molecules in intravenous leiomyomatosis

Objective: This study aims to analyze the clinicopathological characteristics of patients with intravenous leiomyoma (IVL), and to explore the expression characteristics and diagnostic value of angiogenesis related molecules in IVL. Methods: The clinicopathological data of 40 patients with IVL at Women's Hospital, School of Medicine, Zhejiang University from January 2013 to April 2021 were reviewed. Log-rank test was performed to compare the difference in recurrence-free survival (RFS) rates among patients with different clinicopathological characteristics. Immunohistochemistry (IHC) staining was performed on 10 angiogenesis related molecules to analyze their expression characteristics in IVL. The sensitivity and specificity of molecules with high expression rates in the diagnosis of IVL were calculated, the receiver operating characteristic curve (ROC) was plotted and the area under ROC (AUC) was calculated to evaluate the diagnostic value. Results: Median age of the 40 patients was 47 (43, 50) years. The clinical manifestations of IVL were atypical with the diagnostic accuracy of preoperative ultrasound was 12.5% (5/40), CT and/or MRI was 26.7% (8/30), and intraoperative frozen section was 30.0% (12/40). The overall recurrence rate of IVL was 10.0% (4/40). The Log-rank test showed that the cumulative recurrence-free survival rate of IVL patients with previous cesarean section (40.9%) was lower than that of those without cesarean section (96.4%) (P<0.05); and their median RFS time was shorter than those without cesarean section (16.4 months vs 22.2 months). The overall positive rates of adrenomedullin (ADM), fibroblast growth factor receptor 1 (FGFR1), vascular endothelial growth factor receptor 3 (VEGFR3) and angiogenin receptor tyrosine kinase receptor 1 (TIE1) were 65.0% (26/40), 75.0% (30/40), 57.5% (23/40) and 50.0% (20/40), respectively. FGFR1 expression intensity and positive rate were higher in tumors with a maximum diameter greater than 5 cm than in tumors with a maximum diameter smaller than 5 cm (P<0.05). The AUC of FGFR1 combined with ADM, VEGFR3, and TIE1 was 0.876 (95%CI: 0.788-0.964, P<0.001). Conclusions: There was no typical clinical manifestation of IVL. A history of the previous cesarean section indicated a lower cumulative recurrence-free survival rate and shorter recurrence interval. It was hard to diagnose IVL by sonography, radiography, or frozen section pathology. FGFR1, ADM, VEGFR3, and TIE1 were all highly expressed in IVL, and the efficacy of the combination of the four molecules in diagnosing IVL was higher than that of imaging and classical vascular endothelial markers, which are expected to be promising molecular diagnostic markers.

Impact of adjuvant chemotherapy on prognosis in intrahepatic cholangiocarcinoma patients underwent radical resection

Objectives: To investigate the clinical value of adjuvant chemotherapy(ACT) in patients with intrahepatic cholangiocarcinoma(ICC) who underwent radical resection and to explore the optimal population that can benefit from ACT. Methods: A retrospective cohort study method was adopted. The clinical and pathological data of 685 patients with ICC who underwent curative intent resection in 10 Chinese hepatobiliary surgery centers from January 2010 to December 2018 were collected;There were 355 males and 330 females. The age(M(IQR)) was 58(14) years (range: 22 to 83 years). Propensity score matching(PSM) was applied to balance the differences between the adjuvant and non-adjuvant chemotherapy groups. Log-rank test was used to compare the prognosis of the two groups of patients. A Bayesian network recurrence-free survival(RFS) prediction model was constructed using the median RFS time (14 months) as the target variable, and the importance of the relevant prognostic factors was ranked according to the multistate Birnbaum importance calculation. A survival prognostic prediction table was established to analyze the population benefiting from adjuvant chemotherapy. Results: Among 685 patients,214 received ACT and 471 did not receive ACT. A total of 124 pairs of patients were included after PSM, and patients in the ACT group had better overall survival (OS) and RFS than those in the non-ACT group(OS: 32.2 months vs. 18.0 months,P=0.003;RFS:18.0 months vs. 10.0 months,P=0.001). The area under the curve of the Bayesian network RFS prediction model was 0.7124. The results of the prognostic factors in order of importance were microvascular invasion (0.158 2),perineural invasion (0.158 2),N stage (0.155 8),T stage (0.120 9), hepatic envelope invasion (0.090 3),adjuvant chemotherapy (0.072 1), tumor location (0.057 5), age (0.042 3), pathological differentiation (0.034 0), sex (0.029 3), alpha-fetoprotein (0.028 9) and preoperative jaundice (0.008 5). A survival prediction table based on the variables with importance greater than 0.1 (microvascular invasion,perineural invasion,N stage,T staging) and ACT showed that all patients benefited from ACT (increase in the probability of RFS≥14 months from 2.21% to 7.68%), with a more significant increase in the probability of RFS≥14 months after ACT in early-stage patients. Conclusion: ACT after radical resection in patients with ICC significantly prolongs the OS and RFS of patients, and the benefit of ACT is greater in early patients.

Predictors of lymphovascular invasion in estrogen receptor positive/Her-2 negative breast cancer patients treated with neoadjuvant chemotherapy.

Lymphovascular invasion (LVI) is considered a high-risk factor for recurrence in early-stage breast cancer, hence examination of LVI in pathological samples is an absolute recommendation. We aim to investigate predictive factors of LVI in preneoadjuvant chemotherapy (NAC) patients with estrogen receptor positive (ER+) and human epidermal growth factor receptor 2 negative (HER2-) molecular subtypes of breast cancer. One hundred and thirty-four patients treated with NAC were included in this study who were ER+/HER2-. The clinical characteristics of the patients, the data obtained from the core needle biopsy before NAC and the LVI status in the pathology that examined after breast surgery were collected. Univariate and multivariate analysis were performed using the logistic regression model. An examination of the association between LVI and clinical-pathological patient characteristics showed that advanced age (>40 years old) (p = 0.021), ductal histology (p = 0.039), and presence of axillary lymph node metastasis (p = 0.005) were predictors of LVI. Independent predictors of LVI in a multivariate logistic model included advanced age (p = 0.037), and the presence of axillary lymph node metastasis prior to NAC (p = 0.006). The median RFS (Recurrence-free survival) time was 22.8 months for all patients. RFS was shorter in patients with LVI (log-rank p = 0.037). Independent predictors of LVI are advanced age and lymph node positivity at the time of diagnosis. Our study is the first study that evaluates pre-NAC predictive factors of LVI in ER+/HER2- breast cancer patients treated with NAC.

Efficacy and Safety of Central Memory T Cells Combined With Adjuvant Therapy to Prevent Recurrence of Hepatocellular Carcinoma With Microvascular Invasion: A Pilot Study.

BackgroundPostoperative adjuvant transcatheter arterial chemoembolization (TACE) following curative hepatectomy has been reported to improve the clinical outcomes of hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI), but more endeavors are required to achieve greater clinical benefit. Central memory T-cell (Tcm) self-transfusion has shown superior antitumor activity in several preclinical studies; however, clinical studies are rare. The aim of this study was to evaluate the clinical benefit and safety of combination treatment with Tcm self-transfusion and TACE as adjuvant treatment in HCC patients with MVI after curative hepatectomy.MethodsFrom October 2016 to September 2018, primary HCC patients with histologically confirmed MVI who underwent curative hepatectomy at the Cancer Hospital of the Chinese Academy of Medical Sciences were recruited for this study. The patients were divided into a Tcm group (combined Tcm self-transfusion with TACE treatment) or a control group (TACE treatment alone) according to their willingness. The recurrence-free survival (RFS), quality-of-life (QOL) score, and adverse events of each patient were recorded within 2 years.ResultsA total of 52 patients were enrolled, and 48 were eligible for the final data analysis. The median follow-up time was 20.5 months (95% CI: 17.05–22.55 months). The median RFS time was 9.5 months in the control group; the cutoff date was not reached in the Tcm group (when the follow-up duration was 12 months, p = 0.049, HR = 0.40; 95% CI: 0.16–0.99). Compared with the control group, 1- and 2-year RFS rates were higher in the Tcm group (72.0% vs. 46.4% and 58.18% vs. 39.14%, respectively). Multivariate analysis did not indicate that Tcm treatment was an independent prognostic factor associated with HCC recurrence (p = 0.107, HR = 2.312; 95% CI: 0.835–6.400), which might be due to the small sample size of this study. Nevertheless, Tcm treatment effectively improved a reduced QOL due to HCC and liver function injury. Finally, the safety profile of Tcm treatment in this study was good, without any serious adverse events.ConclusionsThis pilot study showed that Tcm self-transfusion combined with TACE treatment might be a beneficial adjuvant therapy with good safety for primary HCC patients with MVI after curative hepatectomy.Trial registration numberNCT03575806