Pathological Lymph Node Metastasis Research Articles

A Novel Predictive Model of Pathological Lymph Node Metastasis Constructed with Preoperative Independent Predictors in Patients with Renal Cell Carcinoma.

Introduction: Renal cell carcinoma (RCC) is one of the most common urinary tumors. The risk of metastasis for patients with RCC is about 1/3, among which 30−40% have lymph node metastasis, and the existence of lymph node metastasis will greatly reduce the survival rate of patients. However, the necessity of lymph node dissection is still controversial at present. Therefore, a new predictive model is urgently needed to judge the risk of lymph node metastasis and guide clinical decision making before operation. Method: We retrospectively collected the data of 189 patients who underwent retroperitoneal lymph node dissection or enlarged lymph node resection due to suspected lymph node metastasis or enlarged lymph nodes found during an operation in Tongji Hospital from January 2016 to October 2021. Univariate and multivariate logistic regression and least absolute shrinkage and selection operator (lasso) regression analyses were used to identify preoperative predictors of pathological lymph node positivity. A nomogram was established to predict the probability of lymph node metastasis in patients with RCC before surgery according to the above independent predictors, and its efficacy was evaluated with a calibration curve and a DCA analysis. Result: Among the 189 patients, 54 (28.60%) were pN1 patients, and 135 (71.40%) were pN0 patients. Three independent impact factors were, finally, identified, which were the following: age (OR = 0.3769, 95% CI = 0.1864−0.7622, p < 0.01), lymph node size according to pre-operative imaging (10−20 mm: OR = 15.0040, 95% CI = 1.5666−143.7000, p < 0.05; >20 mm: OR = 4.4013, 95% CI = 1.4892−7.3134, p < 0.01) and clinical T stage (cT1−2 vs. cT3−4) (OR = 3.1641, 95% CI = 1.0336−9.6860, p < 0.05). The calibration curve and DCA (Decision Curve Analysis) showed the nomogram of this predictive model had good fitting. Conclusions: Low age, large lymph node size in pre-operative imaging and high clinical T stage can be used as independent predictive factors of pathological lymph node metastasis in patients with RCC. Our predictive nomogram using these factors exhibited excellent discrimination and calibration.

The Role of Fascin-1 in Human Urologic Cancers: A Promising Biomarker or Therapeutic Target?

Human cancer statistics show that an increased incidence of urologic cancers such as bladder cancer, prostate cancer, and renal cell carcinoma. Due to the lack of early markers and effective therapeutic targets, their prognosis is poor. Fascin-1 is an actin-binding protein, which functions in the formation of cell protrusions by cross-linking with actin filaments. Studies have found that fascin-1 expression is elevated in most human cancers and is related to outcomes such as neoplasm metastasis, reduced survival, and increased aggressiveness. Fascin-1 has been considered as a potential therapeutic target for urologic cancers, but there is no comprehensive review to evaluate these studies. This review aimed to provide an enhanced literature review, outline, and summarize the mechanism of fascin-1 in urologic cancers and discuss the therapeutic potential of fascin-1 and the possibility of its use as a potential marker. We also focused on the correlation between the overexpression of fascin-1 and clinicopathological parameters. Mechanistically, fascin-1 is regulated by several regulators and signaling pathways (such as long noncoding RNA, microRNA, c-Jun N-terminal kinase, and extracellular regulated protein kinases). The overexpression of fascin-1 is related to clinicopathologic parameters such as pathological stage, bone or lymph node metastasis, and reduced disease-free survival. Several fascin-1 inhibitors (G2, NP-G2-044) have been evaluated in vitro and in preclinical models. The study proved the promising potential of fascin-1 as a newly developing biomarker and a potential therapeutic target that needs further investigation. The data also highlight the inadequacy of fascin-1 to serve as a novel biomarker for prostate cancer.

Outcomes of immediate surgery for low-risk papillary thyroid microcarcinoma in patients with or without risky features at surgery.

Active surveillance (AS) is an accepted management option for patients with low-risk papillary thyroid microcarcinoma (PTMC), although some patients undergo immediate surgery (IS). At surgery, patients may have risky features such as adhesion or invasion to the adjacent organs. The surgical outcomes of this subset of patients are unknown. Here, we investigated the surgical and oncological outcomes of these patients in comparison with others. Between 2005 and 2019, 4,635 patients were diagnosed with low-risk PTMC at our institute. Of these, 1,739 patients underwent IS. In total, 114 patients had risky features at surgery (risky feature group), while the remaining 1,625 did not (no-risky feature group). The median follow-up periods in the risky and no-risky feature groups were 8.5 and 7.6 years, respectively. The risky feature group had higher incidences of tracheal invasion (8.8%), recurrent laryngeal nerve invasion (RLN) (7.9%), and permanent vocal cord paralysis postoperatively (10.0%) and higher frequency of pathological lateral lymph node metastasis (6.1%) than the no-risky feature group (0%, 0%, and 0.2%, and 0%, respectively [p < 0.01]). However, unexpectedly, the former had a lower incidence of high Ki-67 labeling index (1.1%) and lower locoregional recurrence rate (0%) than the latter (8.3% and 0.7, respectively [p < 0.01], not calculable). None of the groups developed distant metastasis or died of the disease. The risky feature group required resection of the trachea and/or the RLN more often than the no-risky feature group. However, unexpectedly, the tumor growth activity in the risky feature group was low, and their oncological outcome was excellent.

Assessment of Monitor Units and Gamma Pass Rate for 6 MV and Flattening Filter Free (FFF) Beams in Volumetric Modulated Arc Therapy (VMAT)

Background: In linear accelerators, the treatment field’s uniform intensity is achieved by including a flattening filter in the beam. However, to produce more conformal dose distributions, contemporary radiotherapy practice now frequently uses fluence and aperture modifying techniques, such as volumetric modulated arc therapy. In these circumstances, the flattening filter in the beam manufacturing process is no longer required. It is therefore necessary to compare the monitor units of 6 MV and flattening filter free plans and how it influences the gamma pass rates to determine which is best for treating cervical cancer with pelvic lymph node metastasis. Methods: VMAT plans for fifteen patients with cervical cancer with pathological pelvic lymph node metastasis were included in this study. Each patient had two VMAT plans using conventional 6 MV beam with flattening filter and one with flattening filter free beam (FFF). The VMAT plans were made using two arcs, and then recalculated to give the planned dose distribution to the detectors in a Delta4 phantom. The VMAT plans were irradiated on the Delta4 phantom using an Elekta linear accelerator (6 MV). Results: The mean monitor unit for the 6 MV plans was 506.3 MU and a standard deviation of 48.6 while that of the FFF plans had a mean MU of 701.5 with a standard deviation of 87.6. The total monitor units (MUs) for the FFF plans were significantly greater than the 6 MV plans (p = 6.1 × 10-5). Conclusion: Flattening filter free (FFF) plans require more numbers of monitor units in comparison to conventional 6 MV filtered beams for external radiation of cervical cancer with pelvic lymph nodes involvement.

Tumour location predicts occult N1 nodal metastasis in clinical stage I non-small-cell lung cancer.

Pathological lymph node metastases are often observed in patients with clinical N0 lung cancer. Identifying preoperative predictors of occult hilar nodal metastasis (OHNM) is important in determining the surgical procedure in patients with clinical stage I non-small-cell lung cancer. This study aimed to determine the frequency and predictors of OHNM by tumour location in these patients. Between April 2007 and May 2019, data of patients who underwent lobectomy or segmentectomy for clinical stage I pure-solid non-small-cell lung cancer were retrospectively reviewed. The ratio of the distance from the pulmonary hilum to the proximal side of the tumour to the distance from the pulmonary hilum to the visceral pleural surface through the centre of the tumour, named 'distance ratio (DR)', was calculated. The relationship of the DR with clinicopathological findings and prognosis was discussed. A total of 357 patients were enrolled. OHNM frequency was 14.6%. Patients were divided into 2 groups based on whether the DR was ≤0.67 (central type) or >0.67 (peripheral type). The frequency of OHNM was significantly higher in the DR ≤0.67 group (21.5% vs 7.4%; P < 0.001). Multivariable analysis revealed that DR was the only independent preoperative predictor of OHNM (odds ratio, 3.63; 95% confidence interval, 1.83-7.18; P < 0.001). The frequency of OHNM was significantly lower in peripheral-type lung cancer; therefore, tumour location was the most important preoperative predictor of OHNM.

Artificial Intelligence-Based Prediction of Recurrence after Curative Resection for Colorectal Cancer from Digital Pathological Images.

To develop an artificial intelligence-based model to predict recurrence after curative resection for stage I-III colorectal cancer from digitized pathological slides. In this retrospective study, 471 consecutive patients who underwent curative resection for stage I-III colorectal cancer at our institution from 2004 to 2015 were enrolled, and 512 randomly selected tiles from digitally scanned images of hematoxylin and eosin-stained tumor tissue sections were used to train a convolutional neural network. Five-fold cross-validation was used to validate the model. The association between recurrence and the model's output scores were analyzed in the test cohorts. The area under the receiver operating characteristic curve of the cross-validation was 0.7245 [95% confidence interval (CI) 0.6707-0.7783; P < 0.0001]. The score successfully classified patients into those with better and worse recurrence free survival (P < 0.0001). Multivariate analysis revealed that a high score was significantly associated with worse recurrence free survival [odds ratio (OR) 1.857; 95% CI 1.248-2.805; P = 0.0021], which was independent from other predictive factors: male sex (P = 0.0238), rectal cancer (P = 0.0396), preoperative abnormal carcinoembryonic antigen (CEA) level (P = 0.0216), pathological T3/T4 stage (P = 0.0162), and pathological positive lymph node metastasis (P < 0.0001). The artificial intelligence-based prediction model discriminated patients with a high risk of recurrence. This approach could help decision-makers consider the benefits of adjuvant chemotherapy.

Pathological multifocality is not a prognosis factor of papillary thyroid carcinoma: a single-center, retrospective study

IntroductionNon-total thyroidectomy (non-TTx) is a widely accepted operative procedure for low-risk papillary thyroid carcinoma (PTC). PTC patients preoperatively diagnosed with unifocal disease are often revealed as having multifocal foci by microscopy. The present study determined whether or not patients with clinically unifocal, but pathologically multifocal non-high-risk PTC treated with non-TTx have an increased risk of a poor prognosis compared to those with pathologically unifocal PTC.Materials and methodsPTC patients diagnosed as unifocal preoperatively who underwent non-TTx were multifocal in 61 and unifocal in 266 patients microscopically. Oncologic event rates were compared between pathologically multifocal and unifocal PTC patients.ResultsPathological multifocality was associated with positive clinical lymph node metastasis (cN1) (odds ratio [OR] 4.01, 95% confidence interval [CI]: 1.91–8.04) and positive pathological lymph node metastasis (pN1) in > 5 nodes (OR 3.68, 95% CI: 1.60–8.49). No patients died from PTC. There was no significant difference in the disease-free survival rate, remnant thyroid disease-free survival rate, lymph node disease-free survival rate, or distant disease-free survival rate between the two groups. Recurrence in pathologically multifocal PTC patients was locoregional in all cases and able to be salvaged by reoperation. Cox proportional hazard model analyses showed no significant difference in recurrence rates with regard to pathological multifocality and cN or number of pNs.ConclusionThe prognosis of PTC with pathological multifocality treated by non-TTx was not inferior to that of unifocal PTC. Immediate completion thyroidectomy is not necessary when microscopic foci are proven.

The comparative study for survival outcome of locally advanced cervical cancer treated by neoadjuvant arterial interventional chemotherapy or intravenous chemotherapy followed by surgery or concurrent chemoradiation

ObjectiveThis study aimed to compare the survival outcome of 3 different treatment groups (arterial interventional chemotherapy or intravenous chemotherapy or concurrent chemoradiotherapy) for locally advanced cervical cancer.MethodsA total of 187 patients with pathological stage IB3–IIB cervical cancer (cervical squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma) hospitalized in the First Affiliated Hospital of Zhengzhou University from January 2013 to May 2019 were included. Therefore, this article is a retrospective study. We collected data from all eligible patients. And all according to the treatment methods at that time, they were divided into three subgroups: (1) 40 patients who received neoadjuvant arterial interventional chemotherapy + surgery + postoperative chemotherapy (IA-NAC + RS), (2) 63 patients who received neoadjuvant intravenous chemotherapy + surgery + postoperative chemotherapy (IV-NAC + RS), (3) 84 patients who only received concurrent chemoradiotherapy (CCRT). Notably, 108 of these patients met the 5-year follow-up period, and 187 patients met the 3-year follow-up period only. Consequently, we compared 5-year survival and 3-year survival separately. The prognosis (5-year survival and 3-year survival) of the three groups and the chemotherapy efficacy, intraoperative blood loss, operation time, and postoperative pathological risk factors of different subgroups were compared.Results(1) There were no significant differences in the 3-year overall survival (OS) rate, 3-year progression-free survival (PFS) rate, 5-year OS rate, and 5-year PFS rate among the three subgroups (p > 0.05). (2) The chemotherapy response rates of IA-NAC+RS group (37.5%) and IV-NAC+RS group (25.4%) were comparable (p > 0.05). (3) The intraoperative blood loss in the IA-NAC+RS group (average 92.13±84.09 mL) was significantly lower than that in the IV-NAC+RS group (average 127.2±82.36 mL) (p < 0.05). (4) The operation time of the IA-NAC+RS group (average 231.43±63.10 min) and the IV-NAC+RS group (average 219.82±49.11 min) were comparable (p > 0.05). (5) There were no significant differences between the IA-NAC+RS group and IV-NAC+RS group in pathological lymph node metastasis, parametrial invasion, and involvement of lymphovascular space (p > 0.05).ConclusionsNeoadjuvant chemotherapy combined with surgery had the same long-term survival benefit as concurrent chemoradiotherapy.

Involvement in the tumor-infiltrating CD8+ T cell expression by the initial disease of remnant gastric cancer

BackgroundRemnant gastric cancer (RGC) has been increasing for various reasons such as a longer life span, medical progress, and others. It generally has a poor prognosis, and its mechanism of occurrence is unknown. The purpose of this study was to evaluate the clinicopathological features of and clarify the oncological features of RGC.MethodsBetween January 2002 and January 2017, 39 patients with RGC following distal gastrectomy underwent curative surgical resection at the Okayama University Hospital; their medical records and immunohistochemically stained extracted specimens were used for retrospective analysis.ResultsOn univariate analysis, initial gastric disease, pathological lymph node metastasis, and pathological stage were the significant factors associated with poor overall survival (p=0.014, 0.0061, and 0.016, respectively). Multivariate analysis of these 3 factors showed that only initial gastric disease caused by malignant disease was an independent factor associated with a poor prognosis (p=0.014, hazard ratio: 4.2, 95% confidence interval: 1.3–13.0). In addition, tumor-infiltrating CD8+ T cells expression was higher in the benign disease group than in the malignant group (p=0.046).ConclusionsInitial gastrectomy caused by malignant disease was an independent poor prognostic factor of RGC, and as one of the causes, lower level of tumor-infiltrating CD8+ T cells in RGC may involve in.

Glucose metabolic heterogeneity correlates with pathological features and improves survival stratification of resectable lung adenocarcinoma.

We investigated whether glycolytic heterogeneity correlated with histopathology, and further stratified the survival outcomes pertaining to resectable lung adenocarcinoma. We retrospectively analyzed the 18F-fluorodeoxyglucose positron emission tomography-derived entropy and histopathology from 128 patients who had undergone curative surgery for lung adenocarcinoma. Disease-free survival (DFS) and overall survival (OS) were analyzed using univariate and multivariate Cox regression models. Independent predictors were used to construct survival prediction models. Entropy significantly correlated with histopathology, including tumor grades, lympho-vascular invasion, and visceral pleural invasion. Furthermore, entropy was an independent predictor of unfavorable DFS (p = 0.031) and OS (p = 0.004), while pathological nodal metastasis independently predicted DFS (p = 0.009). Our entropy-based models outperformed the traditional staging system (c-index = 0.694 versus 0.636, p = 0.010 for DFS; c-index = 0.704 versus 0.630, p = 0.233 for OS). The models provided further survival stratification in subgroups comprising different tumor grades (DFS: HR = 2.065, 1.315, and 1.408 for grade 1-3, p = 0.004, 0.001, and 0.039, respectively; OS: HR = 25.557, 6.484, and 2.570, for grade 1-3, p = 0.006, < 0.001, and = 0.224, respectively). The glycolytic heterogeneity portrayed by entropy is associated with aggressive histopathological characteristics. The proposed entropy-based models may provide more sophisticated survival stratification in addition to histopathology and may enable personalized treatment strategies for resectable lung cancer.

Predictive model for the preoperative assessment and prognostic modeling of lymph node metastasis in endometrial cancer

Lymph node metastasis (LNM) is a well-established prognostic factor in endometrial cancer (EC). We aimed to construct a model that predicts LNM and prognosis using preoperative factors such as myometrial invasion (MI), enlarged lymph nodes (LNs), histological grade determined by endometrial biopsy, and serum cancer antigen 125 (CA125) level using two independent cohorts consisting of 254 EC patients. The area under the receiver operating characteristic curve (AUC) of the constructed model was 0.80 regardless of the machine learning techniques. Enlarged LNs and higher serum CA125 levels were more significant in patients with low-grade EC (LGEC) and LNM than in patients without LNM, whereas deep MI and higher CA125 levels were more significant in patients with high-grade EC (HGEC) and LNM than in patients without LNM. The predictive performance of LNM in the HGEC group was higher than that in the LGEC group (AUC = 0.84 and 0.75, respectively). Patients in the group without postoperative pathological LNM and positive LNM prediction had significantly worse relapse-free and overall survival than patients with negative LNM prediction (log-rank test, P < 0.01). This study showed that preoperative clinicopathological factors can predict LNM with high precision and detect patients with poor prognoses. Furthermore, clinicopathological factors associated with LNM were different between HGEC and LGEC patients.

Impact of the preoperative clinical N stage on the prognosis of patients with colon cancer.

Although preoperative clinical staging (cStage) is performed for most cancer patients, limited information is currently available on the relationship with postoperative prognosis. We herein investigated the relationship between cStage and prognosis of colon cancer (CC) patients, particularly focusing on the presence or absence of clinical lymph node (LN) metastasis. This was a retrospective study on 840 consecutive patients with colon adenocarcinoma who underwent radical resection at our institution between January 2007 and December 2018. A Kaplan-Meier curve was used to analyse the prognosis of two groups: cN(+)pN(-); a group preoperatively diagnosed with clinical LN metastasis positive, but with no pathological LN metastasis postoperatively, and cN(-)pN(-); a group without clinical and pathological LN metastasis. We also investigated whether a clinical diagnosis is a more accurate prognostic factor than other clinical factors. Among pN(-) cases, the 5-year recurrence-free survival rate was significantly lower in preoperatively diagnosed cN(+) cases than in cN(-) cases (79.4% vs. 95.6%, 3.04 years vs. 3.85 years, p < 0.01). In a multivariate analysis of various preoperative clinical factors in pStage II cases, including high risk factors for pStage II CC, cN(+) was identified as an independent prognostic factor (hazard ratio: 2.06, 95% CI: 1.02-4.27, p=0.04). Preoperatively over-staged cN cases had a poorer prognosis than cases without over-staging, indicating its potential as a prognostic factor. In addition to already known high risk factors in pStage II cases, the preoperative cStage may be an indication for adjuvant chemotherapy.

Prediction of Central Lymph Node Metastasis in cN0 Papillary Thyroid Carcinoma by CT Radiomics

To explore the feasibility of the preoperative prediction of pathological central lymph node metastasis (CLNM) status in patients with negative clinical lymph node (cN0) papillary thyroid carcinoma (PTC) using a computed tomography (CT) radiomics signature. A total of 97 PTC cN0 nodules with CLNM pathology data (pN0, with CLNM, n=59; pN1, without CLNM, n=38) in 85 patients were divided into a training set (n=69) and a validation set (n=28). For each lesion, 321 radiomic features were extracted from nonenhanced, arterial and venous phase CT images. Minimum redundancy and maximum relevance and the least absolute shrinkage and selection operator were used to find the most important features with which to develop a radiomics signature in the training set. The performance of the radiomics signature was evaluated by receiver operating characteristic curves, calibration curves and decision curve analysis . Three nonzero the least absolute shrinkage and selection operator coefficient features were selected for radiomics signature construction. The radiomics signature for distinguishing the pN0 and pN1 groups achieved areas under the curve of 0.79 (95% CI 0.67, 0.91) in the training set and 0.77 (95% CI 0.55, 0.99) in the validation set. The calibration curves demonstrated good agreement between the radiomics score-predicted probability and the pathological results in the two sets (p= 0.399, p=0.191). The decision curve analysis curves showed that the model was clinically useful. This radiomic signature could be helpful to predict CLNM status in cN0 PTC patients.

Study on the Relationship between MMP-2, MMP-9 Gene Polymorphisms, and the Risk of Colorectal Cancer.

Objective The aim of the study is to explore the relationship between matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) gene polymorphisms and the risk of colorectal cancer. Methods From January 2019 to December 2021, 308 patients with colorectal cancer in our hospital were selected to be included in the colorectal cancer group and 300 normal healthy people were included in the control group. We perform genotyping, compare the genotype frequencies between the colorectal cancer group and the control group, calculate the relationship between MMP-2 and MMP-9 gene polymorphisms and disease risk, and analyze the genotype distribution characteristics of colorectal cancer patients with different pathological stages and lymph node metastasis status. The expression levels of serum MMP-2 and MMP-9 in patients with different genotypes were compared. Results The frequency of CC genotype and C gene at the MMP-2 gene−735 (C/T) locus in the colorectal cancer group was higher than that of the control group, and the frequency of TT genotype and T gene at MMP-9 gene−1562 (C/T) locus was a higher control group (P < 0.05). The comparison of genotype and gene frequency distribution of MMP-2 gene−1306 (C/T), −790 (T/G), and MMP-9 gene R668Q and P574R between the colorectal cancer group and the control group (P > 0.05); MMP-2 gene−735 (C/T) locus CC genotype and MMP-9 gene−1562 (C/T) locus TT genotype are dangerous genotypes for colorectal cancer. OR values were 1.490 (95% CI: 1.085–2.047), 1.519 (95% CI: 1.061–2.174); TNM stage III-IV, the proportion of CC genotype and TT genotype at MMP-9 gene−1562 (C/T) locus in patients with lymph node metastasis is higher than that without lymph node metastasis of TNM stage I-II patients (P < 0.05); MMP-2 gene in colorectal cancer patients. Serum MMP-2 levels in patients with CC genotype at 735 (C/T) locus were higher than those with CT + TT genotype, and serum MMP-9 levels in patients with TT genotype at MMP-9 gene−1562 (C/T) locus were higher CT + CC genotype patients (P < 0.05). Conclusion The CC genotype at −735 (C/T) locus of the MMP-2 gene and the TT genotype at−1562 (C/T) locus of the MMP-9 gene are risk genotypes for the development of colorectal cancer.

The Different Evaluative Significance of Enlarged Lymph Nodes on Preoperative CT in the N Stage for Patients with Suspected Subsolid and Solid Lung Cancers

To investigate the clinical value of enlarged mediastinal and/or hilar lymph nodes on CT for patients with lung subsolid and solid nodules. The study was performed on patients who underwent surgical treatment for suspected lung cancer. One hundred seventeen subsolid nodules and 101 solid nodules with enlarged lymph nodes (LNs) were included in the study group. The same number of cases with normal LNs with a balanced distribution of the clinical T stage were randomly selected as the control group for each study group. The pathological statuses of the lymph nodes of these patients proven by histopathology after surgery were collected. Lung solid lesions with enlarged LNs were more prone to lymph node metastasis (37.6% vs. 13.9%, p <0.001). However, there were only two and one metastatic lesions in the subsolid group with and without enlarged LNs, respectively. (2/117 vs. 1/117, p=1.000). No pathological lymph node metastasis was observed in subsolid lesions under clinical stage T1b (cT1b), even though some of them (117/234) with enlarged LNs. The evaluative significance of enlarged LNs on CT is different for subsolid and solid lesions. CT is useful for lymph node evaluation and N staging of solid lesions but may has little value for subsolid lesions. There is a very low possibility of lymph node metastasis occurring in patients with subsolid lesions under cT1b. Enlarged LNs on CT may not be critical in subsequent management and treatment for subsolid nodules.

High expression of Sam68 contributes to metastasis by regulating vimentin expression and a motile phenotype in oral squamous cell carcinoma.

The present study aimed to investigate the clinical and biological significance of Src-associated in mitosis 68 kDa (Sam68) in oral squamous cell carcinoma (OSCC). Immunohistochemical analysis was performed on tissue samples obtained from 77 patients with OSCC. Univariate analysis revealed that the high expression of Sam68 was significantly correlated with advanced pathological T stage (P=0.01), positive lymphovascular invasion (P=0.01), and pathological cervical lymph node metastasis (P<0.01). Moreover, multivariate analysis demonstrated that the high expression of Sam68 was an independent predictive factor for cervical lymph node metastasis (odds ratio, 4.39; 95% confidence interval, 1.49-14.23; P<0.01). These results indicated that high Sam68 expression contributed to tumor progression, especially cervical lymph node metastasis, in OSCC. mRNA sequencing was also performed to assess the changes in the transcriptome between OSCC cells with Sam68 knockdown and control cells with the aim of elucidating the biological roles of Sam68. Gene Ontology enrichment analysis revealed that downregulated differentially expressed genes (DEGs) were concentrated in some biological processes related to epithelial-mesenchymal transition. Among these DEGs, it was established that vimentin was particularly downregulated in these cells. It was also confirmed that Sam68 knockdown reduced the motility of OSCC cells. Furthermore, the immunohistochemical study of vimentin identified the association between vimentin expression and Sam68 expression as well as cervical lymph node metastasis. In conclusion, the present study suggested that the high expression of Sam68 may contribute to metastasis by regulating vimentin expression and a motile mesenchymal phenotype in OSCC.

Surgical outcome predictor analysis following hand-assisted or pure laparoscopic transperitoneal nephroureterectomy using the Taiwan upper urinary tract urothelial carcinoma database.

PurposeTaiwan has a high incidence of upper tract urothelial carcinoma (UTUC). This study aimed to compare the surgical outcomes following transperitoneal hand-assisted laparoscopic nephroureterectomy (TP-HALNU) and transperitoneal pure laparoscopic nephroureterectomy (TP-LNU) from the Taiwan nationwide UTUC collaboration database using different parameters, including surgical volumes.Materials and methodsThe nationwide UTUC collaboration database includes 14 hospitals in Taiwan from the Taiwan Cancer Registry. We retrospectively reviewed the records of 622 patients who underwent laparoscopic nephroureterectomy between July 1988 and September 2020. In total, 322 patients who received TP-LNU or TP-HALNU were included in the final analysis. Clinical and pathological data and oncological outcomes were compared.ResultsOf the 322 patients, 181 and 141 received TP-LNU and TP-HALNU, respectively. There were no differences in clinical and histopathological data between the two groups. No differences were observed in perioperative and postoperative complications. There were no significant differences in oncological outcomes between the two surgical approaches. In the multivariate analysis, the cohort showed that age ≥70 years, positive pathological lymph node metastasis, tumors located in the upper ureter, and male sex were predictive factors associated with an increased risk of adverse oncological outcomes. A surgical volume of ≥20 cases showed a trend toward favorable outcomes on cancer-specific survival [hazard ratio (HR) 0.154, p = 0.052] and marginal benefit for overall survival (HR 0.326, p = 0.019) in the multivariate analysis.ConclusionAlthough different approaches to transperitoneal laparoscopic nephroureterectomy showed no significant differences in surgical outcomes, age, sex, lymph node metastasis, and tumor in the upper ureter in the following period were predictive factors for oncological outcomes. Higher surgical volume did not impact disease-free survival and bladder recurrence-free survival but was associated with improved overall survival and cancer-specific survival. Exploration of unknown influencing factors is warranted.

Analysis of delay in adjuvant chemotherapy in locally advanced rectal cancer.

Adjuvant chemotherapy (AC) after neoadjuvant chemoradiation and surgical resection has been the standard of care for locally advanced rectal cancer. However, there are no evidence-based guidelines regarding the optimal timing of AC for rectal cancer. The objective of this study was to evaluate the effect of AC timing on overall survival for rectal cancer. The National Cancer Database (NCDB) from 2004 to 2016 was queried for primary clinical stage II or III rectal cancer patients who had undergone neoadjuvant chemoradiation followed by surgery and AC. Patients were grouped based on AC initiation: early ≤ 4weeks, intermediate 4-8weeks, and delayed ≥ 8weeks. The primary outcome was overall survival. We identified 8722 patients, of which 905 (10.4%) received early AC, 4621 (53.0%) intermediate AC, and 3196 (36.6%) delayed AC. Pathological lymph-node metastasis (ypN +) was positive in 73% of early AC, 74% intermediate AC, and 63% delayed AC (p < 0.05). The 5-year survival probability was 71.1% (95% CI 68-74%) for early AC, 73.2% (95% CI 72-75%) intermediate AC, and 65.8% (95% CI 64-68%) delayed AC (p < 0.001). Using Cox proportional hazard modeling, patients undergoing delayed AC had an associated decreased survival compared to patients receiving early AC (HR 1.18; 95% CI 1.028-1.353, p = 0.018) or intermediate AC (HR 1.28; 95% CI 1.179-1.395, p < 0.01). Delay in AC administration may be associated with decreased 5-year survival. Compared to early or intermediate AC, patients in the delayed AC group were observed to have increased risk of death, despite having lower proportions with ypN + disease. Patients with higher socioeconomic and education status were more likely to receive early chemotherapy.

Effective dissecting range and prognostic significance of lateral pelvic lymph node dissection for middle-low rectal cancer patients with lateral pelvic lymph node metastasis: Results of a large multicenter lateral node collaborative group in China.

BackgroundLateral pelvic lymph node (LPN) metastasis causes increased lateral local recurrence and poor prognosis. We aimed to investigate the prognostic significance and effective range of dissection for the LPN dissection (LPND) in rectal cancer patients with LPN metastasis.Materials and methodsThrough this large, multicenter retrospective cohort study, we evaluated the therapeutic effect of LPND. From January 2012 to December 2019, 387 rectal cancer patients with clinical evidence of LPN metastasis who underwent total mesorectal excision with LPND were included in the study. According to pathological findings, they were divided into negative (n = 296) and positive (n = 91) LPN groups. Primary endpoints were 3-year overall survival (OS), recurrence-free survival (RFS), and local recurrence-free survival (LRFS).ResultsThe OS, RFS, and LRFS in the positive group were significantly worse than those in the negative group; However, LPN metastases were not independent prognostic risk factors for LRFS (hazard ratio [HR]: 2.42; 95% confidence interval [CI], 0.77–7.64; P=0.132). Among patients with pathological LPN metastases, LPN metastases to the common and external iliac arteries were independent prognostic risk factors both for OS (HR: 4.74; 95% CI, 1.74–12.90; P=0.002) and RFS (HR: 2.70; 95% CI, 1.16–6.29; P=0.021). No significant difference was observed in the 3-year OS (72.3% vs. 70.2%, P=0.775) and RFS rates (60.9% vs. 52.6%, P=0.408) between patients with metastases to the obturator or internal iliac arteries and patients at N2b stage.ConclusionsLPND may be effective in controlling local recurrence in patients with LPN metastasis but not systemic metastases. Patients with LPN metastasis limited to the internal iliac and obturator regions achieve a long-term survival benefit from LPND, and their prognoses may be comparable to those at the N2b stage. Further metastasis to the external iliac or common iliac region should be considered systemic disease, and LPND should be avoided.Clinical Trial Registration ClinicalTrials.gov, identifier NCT04850027.

Clinical impact of remnant lymphatic invasion on the recurrence of esophageal squamous cell carcinoma after esophagectomy with neoadjuvant chemotherapy.

For stage II and III esophageal squamous cell carcinoma (ESCC), neoadjuvant chemotherapy (NAC) followed by esophagectomy is recommended in the Japanese guidelines for the diagnosis and treatment of esophageal cancer. However, recurrence of ESCC is common regardless of the NAC regimen and surgical method, and NAC demonstrates limited efficacy against recurrence. Therefore, the present study was conducted to identify risk factors of recurrence of ESCC with surgery after NAC. The outcomes of 51 patients who underwent esophagectomy for ESCC after NAC from 2010 to 2017 at Kyushu University Hospital were retrospectively analyzed. A total of 52 patients with ESCC without NAC followed by esophagectomy from 2001 to 2017 were selected for comparison. Among patients who underwent NAC followed by surgery, only lymphatic invasion (LY; hazard ratio, 2.761; 95% CI, 1.86-6.43, P=0.018) was an independent factor significantly associated with 3-year recurrence-free survival in the multivariate analysis. In patients with pathologic lymph node metastasis (pN) and no LY after NAC, there was significantly less recurrence compared with patients with pN and LY (P=0.0085), whereas in patients without LY after NAC, the presence of pN was not significantly associated with recurrence (P=0.2401). There were significantly fewer LY (+) patients in the NAC (+) group (P=0.0158) compared with those in the NAC (−) group. The presence of LY was an independent risk factor for recurrence of ESCC after esophagectomy following NAC. Overall, adjuvant treatment after surgery may be required in cases with remnant LY after NAC.