Poor Differentiation Research Articles

Identification of FOXP1 as a favorable prognostic biomarker and tumor suppressor in intrahepatic cholangiocarcinoma

BackgroundForkhead-box protein P1 (FOXP1) has been proposed to have both oncogenic and tumor-suppressive properties, depending on tumor heterogeneity. However, the role of FOXP1 in intrahepatic cholangiocarcinoma (ICC) has not been previously reported.MethodsImmunohistochemistry was performed to detect FOXP1 expression in ICC and normal liver tissues. The relationship between FOXP1 levels and the clinicopathological characteristics of patients with ICC was evaluated. Finally, in vitro and in vivo experiments were conducted to examine the regulatory role of FOXP1 in ICC cells.ResultsFOXP1 was significantly downregulated in the ICC compared to their peritumoral tissues (p < 0.01). The positive rates of FOXP1 were significantly lower in patients with poor differentiation, lymph node metastasis, invasion into surrounding organs, and advanced stages (p < 0.05). Notably, patients with FOXP1 positivity had better outcomes (overall survival) than those with FOXP1 negativity (p < 0.05), as revealed by Kaplan–Meier survival analysis. Moreover, Cox multivariate analysis showed that negative FOXP1 expression, advanced TNM stages, invasion, and lymph node metastasis were independent prognostic risk factors in patients with ICC. Lastly, overexpression of FOXP1 inhibited the proliferation, migration, and invasion of ICC cells and promoted apoptosis, whereas knockdown of FOXP1 had the opposite role.ConclusionOur findings suggest that FOXP1 may serve as a novel outcome predictor for ICC as well as a tumor suppressor that may contribute to cancer treatment.

The prognostic value of radiological and pathological lymph node status in patients with cervical cancer who underwent neoadjuvant chemotherapy and followed hysterectomy

To investigate the prognostic value of lymph node status in patients with cervical cancer (CC) patients who underwent neoadjuvant chemotherapy (NACT) and followed hysterectomy. Patients in two referral centers were retrospectively analyzed. The baseline tumor size and radiological lymph node status (LNr) were evaluated on pre-NACT MRI. Tumor histology, differentiation and pathological lymph node status (LNp) were obtained from post-operative specimen. The log-rank test was used to compare survival between patient groups. Cox proportional hazards regression models were employed to estimate the hazard ratio (HR) of various factors with progression-free survival (PFS) and overall survival (OS). A total of 266 patients were included. Patients with 2018 FIGO IIIC showed worse PFS compared to those with FIGO IB-IIB (p < 0.001). The response rate in patients with LNp(−) was 64.1% (134/209), significantly higher than that of 45.6% (26/57) in patients with LNp( +) (p = 0.011). Multivariate Cox analysis identified the main independent predictors of PFS as LNp( +) (HR = 3.777; 95% CI 1.715–8.319), non-SCC (HR = 2.956; 95% CI 1.297–6.736), poor differentiation (HR = 2.370; 95% CI 1.130–4.970) and adjuvant radiation (HR = 3.266; 95% CI 1.183–9.019). The interaction between LNr and LNp regarding PFS were significant both for univariate and multivariate (P = 0.000171 and 1.5357e−7 respectively). In patients with LNr( +), a significant difference in PFS was observed between patients with LNp(−) and LNp( +) (p = 0.0027). CC patients with FIGO 2018 stage IIIC who underwent NACT and followed hysterectomy had worse PFS compared to those with IB-IIB. LNp( +), non-SCC, poor differentiation and adjuvant radiation were independent risk factors for PFS. The adverse prognostic value of LNp( +) was more significant in patients with LNr( +).

Prognosis and clinical and molecular characteristics of patients with brain metastasis secondary to pancreatic ductal adenocarcinoma.

635 Background: Pancreatic ductal adenocarcinoma (PDAC) is a disease of poor prognosis, while secondary brain metastasis (Br-M) is reported to occur in less than 1% of patients with PDAC, with only limited data available suggesting that patients with Br-M have even worse prognosis. We sought to evaluate the prognosis, clinical, and molecular characters of patients with Br-M secondary to PDAC. Methods: The Foundry software platform was used to retrospectively query the electronic health records to identify patients diagnosed with Br-M secondary to PDAC from 2005 to 2023; clinical, molecular, and oncologic outcome data were collected. Results: Br-M was diagnosed in 44 patients with PDAC. The median follow-up was 78 months for our cohort while median overall survival (OS) from diagnosis was 47 months (95%CI=34-79 months). The median duration for Br-M detection from PDAC diagnosis was 24 months, while median OS from Br-M diagnosis was only 3 months (95%CI=2-6 months). 48% (n=21) had metastatic disease at diagnosis. Histological grade was assessed for 37 patients of which 51% (n=19) patients had poor differentiation, while 46% had moderate differentiation, and only 1 patient had a well differentiated tumor. Most of our patients received multiple lines of chemotherapy prior to Br-M development, with a median of 4 chemotherapy regimens received. The majority (73%, n=32) had ECOG performance score of 0 or 1 at Br-M diagnosis, also 82% (n=36) patients had elevated CA19-9 prior to Br-M. Metastases to more than one site other than the brain were detected in 73% (n=32), lung metastasis was the most frequently detected, followed by liver then bone (71% n=31, 66% n=29, 39% n=17, respectively). The frontal lobe was the most frequently affected (34%, n=15) followed by cerebellar affection (23%, n=10). Leptomeningeal affection was observed in (18%, n=8) patients. Targeted clinical mutation testing was done for 17 patients, KRAS was mutated in 95% (n=16) of patients, with G12V in 47% (n=8) of patients, G12D in 29% (n=5), and G12R in 18% (n=3), the second most prevalent mutation was TP53, 70% (n=12) then CDKN2A in 18% (n=3) of the patients. Surgical resection for Br-M was performed for 5 patients who had better median OS of 8.6 months followed by patients who underwent stereotactic radiosurgery (n=11) with median OS of 3.3 months, and patients who received whole brain radiation (n=20) with median OS of 2.8 months. Conclusions: This is the largest cohort for patients with Br-M form PDAC reporting thatsecondary Br-M is a late complication, associated with extremely poor prognosis, in patients who received multiple lines of therapy and have widely metastatic disease. The frontal lobe is the most frequently affected site. KRAS was the most frequently detected mutation and G12V subtype was more prevalent. surgical resection for Br-M was associated with better OS.

Development of vasogenic cerebral oedema after CT myelogram with nonionic contrast.

Madam, Cerebral edema is fluid accumulation in brain because of a cerebral injury such as trauma, ischemia, hemorrhage, abscess, tumors, and poisoning. Based on the pathophysiology it is divided into three types cytotoxic, interstitial and vasogenic, among which vasogenic edema is the commonest type. [1] Vasogenic edema is a very rare complication of CT myelogram. A 42-year-old female known case of diabetes, hypertension, focal segmental necrotizing glomerulonephritis, and permanent pacemaker in situ for ASD secundum presented in December 2020 to Aga Khan University Hospital with backache and progressive bilateral lower limb weakness. On clinical examination she was conscious, alert, and oriented. She had a power of 4/5 and +2 reflexes in both the right and left upper limb and a power of 0/5 and absent reflexes in both the lower limbs. Patient was advised CSF studies and CT myelogram. CT myelogram was performed after a lumbar puncture at L3-L4 level. Approximately 12 mL of non-ionic water-soluble contrast was administered into the spinal canal. CT myelogram was normal. CSF studies showed raised protein. Within less than twelve hours she developed altered sensorium and decreased consciousness. Contrast-enhanced CT brain was performed which showed diffuse effacement of cortical sulci with poor gray-white matter differentiation as shown in Figure 1. There was crowding at the foramen magnum with evidence of tonsillar herniation as shown in Figure 2 and 3. Diagnosis of CT myelogram-induced cerebral edema was made. The patient received mannitol along with steroid pulse therapy. There was interval resolution of cerebral edema and tonsillar herniation on follow up CT brain (Figure 4 and 5). Endocrinology was taken onboard for the management of her diabetes. Five doses of pulse therapy were given, and after a five-day admission and observation the patient was discharged in stable condition. CT lumbar myelogram is a well-tolerated commonly performed procedure that employs intrathecal contrast to outline the subarachnoid space. The adverse effects of intrathecal contrast injection include nausea, headache, vomiting, and dizziness due to increase pressure in the subarachnoid spaces. Rare contrast-induced neurotoxicity, status epilepticus seizures and aseptic meningoencephalitis has also been reported with intrathecal and intravascular nonionic contrast agents. [3–5] Cerebral edema is also a rare complication of intrathecal contrast injection with few case reports being described in the literature. [2] We are reporting this case so that clinicians are familiar with this uncommon complication of CT myelogram to start early management for better patient outcome.

Long-term outcomes of endoscopic or surgical resection in T1 colorectal cancer patients: a retrospective cohort study.

The personalized treatments of T1 colorectal cancer (CRC) remains controversial. We compared the long-term outcomes of T1 CRC patients after endoscopic resection (ER) and surgery, and evaluated the risk factors for the long-term prognosis. T1 CRCs after resection at the Cancer Hospital, Chines Academy of Medical Sciences from June 2011 to November 2021 were reviewed. High-risk factors included positive resection margin, poor differentiation, deep submucosal invasion (DSI ≥ 1000 μm), lymphovascular invasion and intermediate/high tumor budding. Comparative analyses were conducted based on three treatment methods: follow-up after ER (Group A), additional surgery after ER (Group B) and initial surgery (Group C). The primary endpoints included recurrence-free survival (RFS) and overall survival (OS). Cox proportional hazard regression models were constructed to identify risk factors for RFS and OS. A total of 528 patients were enrolled (173 patients in Group A, 102 patients in Group B, 253 patients in Group C). The 3-year RFS, 5-year RFS, 3-year OS, and 5-year OS rates were 96.7%, 94.7%, 99.1%, and 97.8%, respectively. In the absence of other high-risk factors, RFS (P = 0.321) and OS (P = 0.155) of patients with DSI after ER were not inferior to those after surgery. Multivariate analyses identified sex (HR 0.379; 95% CI 0.160-0.894), Charlson comorbidities index (CCI) (HR 3.330; 95% CI 1.571-7.062), margin (HR 8.212; 95% CI 2.325-29.006), and budding (HR 3.794; 95% CI 1.686-8.541) as independent predictive factors of RFS, and identified CCI (HR 10.266; 95% CI 2.856-36.899) as an independent predictive factor of OS. The long-term outcomes of ER are comparable to those of surgery in T1 CRC patients with DSI when other high-risk factors are negative. Resection margin, tumor budding, sex, and CCI may be the most important long-term prognostic factors for T1 CRC patients.

Characterizing Immune Infiltration in Esthesioneuroblastoma Subtypes Through Gene Expression Deconvolution

BackgroundEsthesioneuroblastoma (ENB) is a rare cancer deriving from the olfactory mucosa. Among the basal or neural genomic subtypes, the basal subtype is associated with poorer survival, and poor differentiation, and higher levels of tumor-infiltrating immune cells (TIICs). The immune microenvironment of these ENB subtypes remains unclear. We used an established machine-learning algorithm on ENB transcriptomic profiles. MethodsThe authors characterized 22 immune cell populations using the CIBERSORTx deconvolutional machine-learning pipeline on RNAseq data from 18 ENB cases. The characterization aimed to elucidate differences in relative proportions and populations of TIICs between basal and neural ENB. ResultsNo differences in age, Hyams, Dulguerov, IDH2 mutation, or PD-L1 expression were seen between basal and neural subtypes of ENB (p>0.05). No difference in median overall survival was also appreciated (52.0±13.1 vs. 50.0±43.2 months, p=0.5). As a cohort, M2 macrophages were the most abundant subpopulation (14%) followed by naïve B-cells (13%) and CD4 memory resting T cells (12%). No gross differences on CD20, CD4, or CD8 cells/mm2 were apparent on gross histology (p>0.05). However, further analysis showed that activated CD4 memory T cells were significantly increased in the basal ENBs, whereas resting dendritic cells were increased in the neural ENB subtype. The TIIC profiles alone could not differentiate between basal and neural ENB but did suggest immunoprofile differences. ConclusionBasal and neural subtypes display distinct TIIC involvement, which may impact their difference in outcome. These findings provide the framework for further investigation in novel immunomodulation strategies for ENB.

Role of stromal PD-L1 expression in colorectal liver metastasis

Background and AimThe outcomes of immune checkpoint blockade for colorectal cancer (CRC) treatment are unsatisfactory. Furthermore, the efficacy of immune checkpoint blockade for liver metastasis of various cancer is poor. Here, we investigated the relationship between stromal programmed death-ligand 1 (PD-L1) expression and the prognosis of patients with colorectal cancer liver metastasis (CRLM).MethodsThe present study enrolled 84 CRLM patients who underwent surgery (R0) for CRC. Immunohistochemistry was performed to analyze stromal PD-L1 expression in CRLM.ResultsStromal PD-L1 was expressed in 52.3% of CRLM samples, which was associated with fewer not optimally resectable metastases (p = 0.04). Stromal PD-L1 also tended to associate with a lower tumor grade (p = 0.08). Stromal PD-L1-positive patients had longer overall survival (p = 0.003). Multivariate analysis identified stromal PD-L1 expression (p = 0.008) and poorer differentiation (p < 0.001) as independent prognostic indicators. Furthermore, stromal PD-L1 expression was correlated to a high number of tumor-infiltrating lymphocytes (TILs). Stromal PD-L1– and low TIL groups had shorter OS than stromal PD-L1 + and high TIL groups (46.6% vs. 81.8%, p = 0.05) Stromal PD-L1-positive patients had longer disease-free survival (DFS) (p = 0.03) and time to surgical failure (p = 0.001). Interestingly, stromal PD-L1 expression was positively related to the desmoplastic subtype (p = 0.0002) and inversely related to the replacement subtype of the histological growth pattern (p = 0.008).ConclusionsStromal PD-L1 expression may be a significant prognostic marker for CRLM.

Abstract C045: Multiplex fluorescent immunohistochemistry reveals immune microenvironment alterations in COMPASS-like complex gene mutated pancreatic cancer

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) is highly resistant to chemoradiation and immune therapies. There is limited biomarker to identify subsets of PDAC that responds to immunotherapy or targeted therapy. We have identified a subset of PDACs (approximately 25%) carrying COMPASS-like complex (CLC) gene mutations. Analysis of the clinicopathologic and molecular features of this PDAC subset revealed that these tumors are an aggressive group of PDACs with poor or squamous histologic differentiation, increased rates of TP53 mutations, and poor patient survival compared to control PDACs. Our preliminary data showed that PDACs carrying mutations in two members of the CLC genes (KDM6A and KMT2D) have immunosuppressive tumor microenvironment (TME), suggesting that CLC genes are candidate biomarkers for immunotherapy. However, a comprehensive analysis of the immune composition, immune checkpoint expression, and the relationship between tumor cells and immune cells in CLC gene mutated PDACs compared to controls has not been performed. In this study, we characterized the immune composition in CLC gene mutated PDACs compared to paired control PDACs using tyramide signal amplification multiplex fluorescent immunohistochemistry (mfIHC). Methods: Human PDAC tissue slides were stained with 7 markers using mfIHC and allowed for phenotyping of 7 cell types: PD-L1- epithelial cells (ECs) (pancytokeratin+PD-L1-), PD-L1+ ECs (pancytokeratin+PD-L1+), cytotoxic T lymphocytes (CTLs) (CD3+CD8+), helper T cells (CD3+CD8-FoxP3-), Tregs (CD3+CD8-FoxP3+), PD-L1- antigen presenting cells (APCs) (CD163+PD-L1-), and PD-L1+ APCs (CD163+PD-L1+). Random image sections were selected in each sample (5~8 sections per sample) and divided into wild-type (WT) group (n=49) and mutant group (n=49) and analyzed using inForm Cell Analysis software. Tissue segmentation training was performed to separate stromal and epithelial elements. Cell percentage, cell density, and nearest neighbor distance of each cell type were calculated using R program. Results: There is an increased infiltration of T cells, Tregs, and helper T cells in the epithelial component of the mutant group compared with WT group. The epithelial cells are more frequent to express PD-L1. Interestingly, we also observed more Treg infiltration in the stromal component and total tissue in the mutant group compared with WT group. The CTLs are more engaged with the epithelial cells, regardless of their PD-L1 status, in the mutant group compared with WT group. Conclusions: Our results provide insight into the effects of CLC gene mutations on shaping the immune microenvironment of PDAC and suggest that CLC gene mutated PDACs have a different immune microenvironment than other PDACs and may respond differently to immunotherapy. Citation Format: Shungang Zhang, Jake McGue, Elaina Daniels, Hong Sun Kim, Dafydd Thomas, Jiaqi Shi. Multiplex fluorescent immunohistochemistry reveals immune microenvironment alterations in COMPASS-like complex gene mutated pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C045.

Clinical role of pretreatment albumin-to-alkaline phosphatase ratio in lung cancer: a meta-analysis

The association between pretreatment albumin-to-alkaline phosphatase ratio (AAPR) and clinicopathological parameters and prognosis in lung cancer is unclear. The study aimed to identify the clinical role of pretreatment AAPR among lung cancer patients. Several databases were searched for relevant studies. The primary outcome and secondary outcome were long-term survival including the overall survival (OS) and progression-free survival (PFS) and clinicopathological characteristics, respectively. The hazard ratios (HRs) and relative risks (RRs) with 95% confidence intervals (CIs) were combined. A total of 11 publications involving 10,589 participants were included in this meta-analysis. The pooled results manifested that a lower pretreatment AAPR predicted poorer OS (HR = 0.65, 95% CI 0.59–0.71, P < 0.001) and PFS (HR = 0.68, 95% CI 0.59–0.78, P < 0.001). Furthermore, subgroup analysis for the OS and PFS based on the pathological type and treatment showed similar results and pretreatment AAPR was significantly associated with worse prognosis. Besides, pretreatment AAPR was significantly associated with male (RR = 1.08, 95% CI 1.03–1.13, P < 0.001), poor differentiation (RR = 1.33, 95% CI 1.03–1.73, P = 0.029), advanced T stage (RR = 1.25, 95% CI 1.03–1.52, P = 0.026), N stage (RR = 1.34, 95% CI 1.15–1.55, P < 0.001) and TNM stage (RR = 1.14, 95% CI 1.06–1.223, P < 0.001). Therefore, pretreatment AAPR is significantly related to prognosis and tumor stage in lung cancer and patients with a lower pretreatment AAPR are more likely to experience poor survival and advanced tumor stage.

Investigation of the association between the Toll-like receptor 1 rs4833095 variation and gastric adenocarcinoma recurrence.

Toll-like receptors (TLRs) are a family of transmembrane receptors that play key roles in identifying invading pathogens and activating innate immunity. TLR1 has been reported to be associated with the risk of gastric cancer (GC) but that was based on only a simple statistical analysis. We genotyped the TLR1 in 526 GC patients to investigate the association between the variation and gastric cancer survival by the multiplex polymerase chain reaction and sequencing method. The rs4833095 variation (chr4:38798089 [GRCh38. p14], T>C) in the TLR1 gene was genotyped in 526 patients who underwent GC resection. The associations between genotype, survival, and recurrence were investigated. The potential role of TLR1 in stomach cancer was investigated using clinical data from formalin-fixed, paraffin-embedded tissue samples. Patients with the T/C and C/C genotypes of rs4833095 had a lower risk of recurrence than those with the T/T genotype. Recurrence-free periods were substantially longer in patients with the T/C or C/C genotypes (22.6 and 22.3 months, respectively) than in those with the T/T genotype (20.7 months). Patients with the T/C or C/C genotype, low expression levels of VEGF1, high expression levels of ERBB2 and ERCC1, the absence of cancer nodules, a tumor size of less than 5cm, and poor differentiation had a considerably reduced risk of recurrence. TLR1 rs4833095 was correlated with the postresection prognosis of patients with gastric cancer, suggesting that TLR1 may have a role in the onset or progression of gastric cancer.

Combining pathological risk factors and T, N staging to optimize the assessment for risk stratification and prognostication in low-risk stage III colon cancer

BackgroundThis study aimed to investigate the combined pathological risk factors (PRFs) to stratify low-risk (pT1-3N1) stage III colon cancer (CC), providing a basis for individualized treatment in the future.Patients and methodsPRFs for low-risk stage III CC were identified using COX model. Low-risk stage III CC was risk-grouped combining with PRFs, and survival analysis were performed using Kaplan–Meier. The Surveillance, Epidemiology, and End Results (SEER) databases was used for external validation.ResultsNine hundred sixty-two stage III CC patients were included with 634 (65.9%) as low risk and 328 (34.1%) as high risk. Poor differentiation (OS: P = 0.048; DFS: P = 0.011), perineural invasion (OS: P = 0.003; DFS: P < 0.001) and tumor deposits (OS: P = 0.012; DFS: P = 0.003) were identified as PRFs. The prognosis of low-risk CC combined with 2 PRFs (OS: HR = 3.871, 95%CI, 2.004–7.479, P < 0.001; DFS: HR = 3.479, 95%CI, 2.158–5.610, P < 0.001) or 3 PRFs (OS: HR = 5.915, 95%CI, 1.953–17.420, P = 0.002; DFS: HR = 5.915, 95%CI, 2.623–13.335, P < 0.001) was similar to that of high-risk CC (OS: HR = 3.927, 95%CI, 2.317–6.656, P < 0.001; DFS: HR = 4.132, 95%CI, 2.858–5.974, P < 0.001). In the SEER database, 18,547 CC patients were enrolled with 10,023 (54.0%) as low risk and 8524 (46.0%) as high risk. Low-risk CC combined with 2 PRFs (OS: HR = 1.857, 95%CI, 1.613–2.139, P < 0.001) was similar to that of high-risk CC without PRFs (HR = 1.876, 95%CI, 1.731–2.033, P < 0.001).ConclusionCombined PRFs improved the risk stratification of low-risk stage III CC, which could reduce the incidence of undertreatment and guide adjuvant chemotherapy.

Clinical impact of ampulla of Vater cancer subtype classification based on immunohistochemical staining

BackgroundThe histological subtype is an important prognostic factor for ampulla of Vater (AoV) cancer. This study proposes a classification system for the histological subtyping of AoV cancer based on immunohistochemical (IHC) staining and its prognostic significance.MethodsSeventy-five AoV cancers were analyzed for cytokeratin 7 (CK7), CK20, and causal-type homeobox transcription factor 2 (CDX2) expression by IHC staining. We differentiated the subtypes (INT, intestinal; PB, pancreatobiliary; MIX, mixed; NOS, not otherwise specified) into classification I: CK7/CK20, classification II: CK7/CK20 or CDX2, classification III: CK7/CDX2 and examined their associations with clinicopathological factors.ResultsClassifications I, II, and III subtypes were INT (7, 10, and 10 cases), PB (43, 37, and 38 cases), MIX (13, 19, and 18 cases), and NOS (12, 9, and 9 cases). Significant differences in disease-free survival among the subtypes were observed in classifications II and III using CDX2; the PB and NOS subtype exhibited shorter survival time compared with INT subtype. In classification III, an association was revealed between advanced T/N stage, poor differentiation, lymphovascular invasion (LVI), the PB and NOS subtypes, and recurrence risk. In classification III, the subtypes differed significantly in T/N stage and LVI. Patients with the PB subtype had advanced T and N stages and a higher incidence of LVI.ConclusionsClassification using CDX2 revealed subtypes with distinct prognostic significance. Combining CK7 and CDX2 or adding CDX2 to CK7/CK20 is useful for distinguishing subtypes, predicting disease outcomes, and impacting the clinical management of patients with AoV cancer.

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.

Prognostic significance of FAT10 expression in malignant tumors: a systematic review and meta-analysis.

Aim: FAT10, a ubiquitin-like modifier protein, influences apoptosis, DNA damage response and tumor growth, with unclear effects on cancer prognosis.Methods: We reviewed FAT10 expression's impact on malignancy prognosis through a systematic review and meta-analysis, including studies up to September 2023 from PubMed, EMBASE and Web of Science.Results: From 18 studies involving 2513 patients, FAT10 overexpression significantly reduced overall and disease-free survival across various tumors, indicating correlations with advanced disease stage, poor differentiation, lymph node metastasis and larger tumor size.Conclusion: FAT10's overexpression suggests a negative prognostic value in cancer, meriting further investigation.PROSPERO Registration Number: CRD42023431287.

Beyond graft function impairment after liver transplantation: the prolonged cold ischemia time impact on recurrence of hepatocellular carcinoma after liver transplantation-a single-center retrospective study.

Hepatocellular carcinoma (HCC) is one of the malignant tumors responsible for high mortality and recurrence rates. Although liver transplantation (LT) is an effective treatment option for HCC, ischemia-reperfusion injury (IRI) is a contributor to HCC recurrence after LT. Moreover, prolonged cold ischemia time (CIT) is a risk factor for IRI during LT, and there is insufficient clinical evidence regarding the impact of CIT on HCC recurrence after LT. This retrospective study analyzed 420 patients who underwent LT for HCC between February 2015 and November 2020 at The First Affiliated Hospital, Sun Yat-sen University. The duration of CIT was defined as the time from clamping of the donor aorta until portal reperfusion. A total of 133 patients (31.7%) experienced tumor recurrence after LT, and CIT > 568 min was the independent risk factor for HCC recurrence (OR, 2.406; 95% CI [1.371-4.220]; p = 0.002). Multivariate Cox's regression analysis revealed that the recipients' gender, exceeding Milan criteria, poor differentiation, and alpha-fetoprotein (AFP) ≥400 ng/ml in CIT > 568 min group were independent risk factors for disease-free survival. The peak 7-day postoperative alanine aminotransferase (ALT) level (p<0.001), the peak 7-day postoperative aspartate aminotransferase (AST) level (p<0.001), the peak 7-day postoperative peak total bilirubin (TBIL) level (p=0.012), and the incidence of early allograft dysfunction (EAD) (p=0.006) were significantly higher in the CIT > 568 min group compared to the CIT ≤ 568 min group. Moreover, the amount of fresh frozen plasma (FFP) infusion during the operation increased (p=0.02), and the time of mechanical ventilation postoperative was longer (p=0.045). An effective strategy to improve the prognosis is to reduce CIT; this strategy lowers the recurrence of HCC in patients undergoing LT, especially those within the Milan criteria.

Patterns of lymph node metastasis in 441 patients with sinonasal squamous cell carcinoma.

Due to the rarity of sinonasal squamous cell carcinoma (SNSCC), the distribution patterns of lymph node metastasis (LNM), the relationship between LNM and prognosis, and the optimal treatment of LNM lack sufficient evidence-based support. To investigate the patterns of LNM in SNSCC and evaluate the impact of LNM on prognosis. This was a retrospective cohort study. The medical records of 441 patients with SNSCC between 2009 and 2022 in one institution were retrospectively reviewed. We assessed the incidence, the distribution of LNM, and the relationship between LNM and long-term survival. Seventy-three out of 441 patients (16.6%) presented LNM initially. Among the 73 patients, 34 patients (46.6%) had LNM in the region of ipsilateral level II; 22 patients (30.1%) had positive retropharyngeal lymph nodes; 20 patients (27.4%) had LNM in the region of ipsilateral level Ib; and nine patients (12.3%) had evidence of parotid LNM. Poor differentiation (p = 0.001), nasal cavity (p = 0.018), skin involvement (p = 0.036), and nasopharynx involvement (p = 0.009) were the risk factors for LNM. In the univariate and multivariate analyses, the overall survival (p = 0.25), progression-free survival (p = 0.22), regional failure-free survival (p = 0.20), and distant metastasis-free survival (p = 0.14) rates were not significantly decreased by the LNM. After the propensity score matching, LNM was still not correlated with poor long-term survival. The incidence of retropharyngeal and parotid LNM was higher than in previous studies. At initial diagnosis, the risk factors for LNM were identified, and LNM was not associated with poor survival outcomes.

Exploring the MRI and Clinical Features of P53-Mutated Hepatocellular Carcinoma.

To study the MRI features (based on LI-RADS) and clinical characteristics of P53-mutated hepatocellular carcinoma (HCC) patients. This study enrolled 344 patients with histopathologically confirmed HCC (P53-mutated group [n = 196], non-P53-mutated group [n = 148]). We retrospectively evaluated the preoperative MRI features, clinical and pathologic features of the lesions and assigned each lesion according to the LI-RADS. MRI findings, clinical features, and pathologic findings were compared using the Student's t test, χ2 test, and multivariable regression analysis. Most HCC patients were categorized as LR-5. On multivariate analysis, the Edmondson-Steiner grade (odds ratio, 2.280; 95% CI: 1.268, 4.101; p = 0.006) and rim enhancement (odds ratio, 2.517; 95% CI: 1.095, 5.784; p = 0.030) were found to be independent variables associated with P53-mutated HCC. In the group of HCC lesions with the largest tumor diameter (LTD) greater than or equal to 10mm and less than or equal to 20mm, enhancing capsule was an independent predictor of P53-mutated HCC (odds ratio, 6.200; 95% CI: 1.116, 34.449; p = 0.037). Among the HCC lesions (20 mm ˂ LTD ≤ 50 mm), corona enhancement (odds ratio, 2.102; 95% CI: 1.022, 4.322; p = 0.043) and nodule-in-nodule architecture (odds ratio, 2.157; 95% CI: 1.033, 4.504; p = 0.041) were found to be independent risk factors for P53 mutation. Among the HCC lesions (50 mm ˂ LTD ≤ 100 mm), diameter (odds ratio, 1.035; 95% CI: 1.001, 1.069; p = 0.044) and AFP ≥ 400 (ng/mL) (odds ratio, 3.336; 95% CI: 1.052, 10.577; p = 0.041) were found to be independent variables associated with P53-mutated HCC. Poor differentiation and rim enhancement are potential predictive biomarkers for P53-mutated HCC, while HCCs of different diameters have different risk factors for predicting P53 mutations.

Expression of RSK4 protein in non-small cell lung cancer tissues, adjacent tissues and its correlation with clinicopathological features.

To evaluate the expression of Ribosomal S6 kinase 4 (RSK4) protein in non-small cell lung cancer (NSCLC) tissues and adjacent non-tumor tissues, and to elucidate its correlation with clinicopathological features of NSCLC. We analyzed 100 NSCLC patients treated at the Second Affiliated Hospital of Zhejiang University School of Medicine from June 2020 to June 2022. Patient demographics and clinical data, including gender, age, history of diabetes, tumor location, degree of tumor differentiation, lymph node metastasis, and clinical stage, were collected. RSK4 protein expression was assessed in tissue samples via immunohistochemical staining. RSK4 protein was positively expressed in 35.00% of cancerous tissues, significantly lower than the 69.00% observed in adjacent non-tumor tissues (P < 0.05). Patients with lower tumor differentiation, advanced Tumor Node Metastasis (TNM) stages, and lymph node metastases showed significantly reduced RSK4 expression compared to those with higher differentiation, earlier TNM stages, and no lymph node metastases (all P < 0.05). Cox regression analysis indicated that TNM stage, low differentiation, and lymph node metastases significantly influenced RSK4 expression (all P < 0.05). Survival analysis revealed a higher positive prognosis survival rate of 74.29% (26/35) among patients with positive RSK4 expression, versus 53.85% (35/65) in those with negative expression (P < 0.05). Spearman correlation analysis demonstrated a significant positive correlation of RSK4 expression with TNM stage, lymph node metastasis, and patient prognosis (all P < 0.05). Positive RSK4 expression in NSCLC tissues is significantly correlated with advanced cancer stage, poor differentiation, and presence of lymph node metastasis, suggesting a potential tumor suppressor role for RSK4 in NSCLC. This association underscores its prognostic relevance in NSCLC patients.

Detection of γ-OHPdG in Circulating Tumor Cells of Patients With Hepatocellular Carcinoma as a Potential Prognostic Biomarker of Recurrence

Background and AimsBlood-based biomarkers for hepatocellular carcinoma (HCC) and its recurrence is lacking. We previously showed that hepatic γ-hydroxy-1,N2-propano-2′-deoxyguanosine (γ-OHPdG), an endogenous DNA adduct derived from acrolein by lipid peroxidation, increased during hepatocarcinogenesis. Additionally, higher hepatic γ-OHPdG from HCC patients after surgery were strongly associated with poor survival (P < .0001) and recurrence-free survival (P = .007) (Fu Y et al., Hepatology, 2018). These findings suggest that γ-OHPdG is a potential prognostic biomarker for HCC and its recurrence. To attain the goal of using γ-OHPdG as a biomarker in future preventive and therapeutic trials, we developed a blood-based method to detect γ-OHPdG in circulating liver tumor cells from HCC patient blood. MethodsWe first established the specificity of anti-γ-OHPdG antibody by determining its dose-response in HepG2 cells treated with acrolein. Then, HepG2 cells in spiked blood of healthy volunteers (HV) and circulating tumor cells (CTCs) from 32 HCC patients were isolated using a RosetteSep™ CD45 Depletion Cocktail and Ficoll Paque. The HCC CTCs identified with anti-asialoglycoprotein receptor 1, a surface protein expressed solely in hepatocytes, were stained with an anti-γ-OHPdG antibody. The number of total HCC CTCs and γ-OHPdG-positive CTCs, as well as the staining intensity, were quantified using a MetaMorph software. As an initial effort toward its clinical application, we also evaluated γ-OHPdG in CTCs from these patients along with certain clinical features. ResultsThe γ-OHPdG antibody specificity was demonstrated by an acrolein concentration-dependent increase of γ-OHPdG-positive HepG2 cells and the intensity of γ-OHPdG staining. The recovery of HepG2 cells from spiked blood was ∼50-60%, and the positivity rate of CTCs in blood from 32 patients with advanced HCC was 97%. The MetaMorph analysis showed a wide variation among patients in total number of CTCs, γ-OHPdG positivity, and staining intensity. Statistical analysis revealed γ-OHPdG in CTCs of these patients appear to be associated with multifocality and poor differentiation. ConclusionsA blood-based method was developed and applied to HCC patients to evaluate the potential of γ-OHPdG in CTCs as a prognostic biomarker.

An MRI radiomics-based model for the prediction of invasion of the lymphovascular space in patients with cervical cancer.

Cervical cancer (CC) remains the second leading cause of cancer-related death in women, and the ability to accurately anticipate the presence or absence of lymphovascular space invasion (LVSI) is critical to maintaining optimal patient outcomes. The objective of this study was to establish and verify an MRI radiomics-based model to predict the status of LVSI in patients with operable CC. The current study performed a retrospective analysis, with 86 patients in the training cohort and 38 patients in the testing group, specifically focusing on patients with CC. The radiomics feature extraction process included ADC, T2WI-SPAIR, and T2WI sequences. The training group data were used for the initial radionics-based model building, and the model predictive performance was subsequently validated using data from patients recruited in the experimental group. The development of the radiomics scoring model has been completed with 17 selected features. The study found several risk factors associated with LVSI. These risk factors included moderate tumor differentiation (P = 0.005), poor tumor differentiation (P = 0.001), and elevated combined sequence-based radiomics scores (P = 0.001). Radiomics scores based on predictive model, combined sequences, ADC, T2WI-SPAIR, and T2WI exhibited AUCs of 0.897, 0.839, 0.815, 0.698, and 0.739 in the training cohort, respectively, with corresponding testing cohort values of 0.833, 0.833, 0.683, 0.692, and 0.725. Excellent consistency was shown by the calibration curve analysis, which showed a higher degree of agreement between the actual and anticipated LVSI status. Moreover, the decision curve analysis outcomes demonstrated the medical application of this prediction model. This investigation indicated that the MRI radiomics model was successfully developed and validated to predict operable CC patient LVSI status, attaining high overall diagnostic accuracy. However, further external validation and more deeper analysis on a larger sample size are still needed.