Regional Lymph Node Metastasis Research Articles

Risk of leptomeningeal metastasis in children with parameningeal rhabdomyosarcoma with intracranial spread

Introduction. Soft tissue tumors account for up to 8 % of all malignant neoplasms in children. According to the international histological classification, about 150 different morphological variants of soft tissue tumors have been registered, of which 45 % are rhabdomyosarcoma (RMS). Most often, RMS occurs in early childhood – the average age of patients at the time of diagnosis is 5 years. The incidence rate of RMS is 0.9 per 100,000 children. In 25 % cases, the initial diagnosis reveals distant metastasis to the lungs, bones, bone marrow, and 8 % – leptomeningeal metastasis. More than 7 % of patients with localized parameningeal RMS develop leptomeningeal metastasis, according to the Rhabdomyosarcoma Study Group. Purpose of the study – report the incidence, prognosis of leptomeningeal metastasis and treatment outcomes in children with intracranial spread of RMS. Materials and methods. The study included 45 patients aged 1 to 17 years with a diagnosis of RMS of parameningeal localization with intracranial spread, who received special treatment from 2003 to 2020. The study included 6 (20 %) patients in whom the tumor developed in early childhood (up to 3 years). The boys predominated – 25 (55.5 %) in the study. The primary tumor spread to the orbit in 7 (15 %) cases, the skull base in 7 (15 %) cases, the middle ear in 4 (8 %) cases, the nasopharynx in 3 (6 %) cases, and the brain substance was affected in 16 (35 %). Metastases in regional lymph nodes were determined in 7 (15 %) patients. Multiple metastatic lesions of bones and bone marrow – 4 (9 %) cases, leptomeningeal metastases – in 2 (4 %). 45 (100 %) patients received drug treatment according to the protocols approved by the Academic Council of the Research Institute of Pediatric Oncology and Hematology at N. N. Blokhin National Medical Research Centerof Oncology, Ministry of Health of Russia. Radiation therapy was performed in 33 (74 %) patients, while total focal dose of 50 Gy was administered to the primary tumor. Affected lymph nodes of the neck were irradiated in 10 (23 %) patients, total focal dose is 45.0 Gy. Surgical treatment was performed in 15 (34 %) patients. Multicomponent treatment was performed in 15 (34 %) patients. Results. During the observation period from 12 months to 14 years, 21 (49 %) patients are alive. 21 (51 %) patients died from tumor progression, 1 (2 %) died from complications of special treatment. Conclusions. The treatment of this group of patients is one of the urgent problems of pediatric oncology, which is based on polychemotherapy, supplemented by intrathecal administration of anticancer drugs and craniospinal irradiation. The development of new therapies requires a multidisciplinary approach to achieve a significant improvement in the survival of children with leptomeningeal metastases RMS of parameningeal localization.

Intertumor heterogeneity of locally advanced gastric cancer.

435 Background: The aim of the present study was to determine to the effect of HER2, dMMR, PD-L1 status in the primary tumor and in metastasis to the regional lymph node of GC patients. Methods: A total of 44 patients with primary loco-regional (N+) gastric adenocarcinoma were recruited, and two formalin-fixed paraffin-embedded (FFPE) tumor-containing blocks of each patient (one block with primary tumor and one block with metastasis to the regional lymph node)were selected for HER2, dMMR, PD-L1 (CPS) immunohistochemical (IHC) assay. Clinicopathological characteristics were recorded, and intertumoral heterogeneity of HER2, dMMR, PD-L1 IHC expression was determined. Results: The study included 19 women and 25 men, 30 patients had Laurén’s intestinal type of cancer, 14 had a Laurén’s diffuse type. In 5 patients (11.4%) overexpression of Her-2 neu was detected, and heterogeneity was detected in all five cases: in three patients with HER2 overexpression in the primary tumor, no overexpression was detected in the metastasis to the regional lymph node, in two cases overexpression was detected in the metastasis, while no overexpression was observed in the primary tumor. 2 patients showed signs of dMMR (4.5%), in one case, heterogeneity in dMMR status was also revealed: signs of dMMR in the primary tumor and its absence in regional metastasis (pMMR). Assessment of PD-L1 status was carried out using the CPS formula. Ten patients (22.7%) had a negative PD-L1 status (CPS=0) both in the primary tumor and in regional metastasis. Positive PD-L1 status in the primary tumor: in 24 patients CPS= 0-5 (54.5%), in 5 patients CPS= 5-10 (11.4%) and 5 patients CPS= 10 or more (11.4% ). Positive PD-L1 status in regional lymph node metastasis: in 24 patients CPS= 0-5 (54.5%), in 5 patients CPS= 5-10 (11.4%) and in 5 patients CPS= 10 or more ( 11.4%). In 5 cases (11.4%) marked heterogeneity in PD-L1 status between the primary tumor and its regional metastasis (1 case with dMMR heterogeneity). Conclusions: The research findings in this paper indicate that the intertumoral heterogeneity of HER2 overexpression is common in GC patients, We highly recommend multi-block HER2 assessment for accurate diagnosis of GC. Given the rarity of status detection dMMR, a study in a larger number of patients is required, however, our data also confirm the presence of heterogeneity in dMMR status, and probably the possibility of metastasis of a more aggressive pMMR clone. Heterogeneity in PD-L1 status is quite rare and amounted to only 11.4%, which also has important practical significance.

Factors Associated with Bone Scintigraphy Positivity in Cholangiocarcinoma

Objective: To examine factors associated with bone scintigraphy (BS) positivity in cases with cholangiocarcinoma (CCA) to help assess appropriate utilization of BS in CCA patients. Material and Methods: This cross-sectional study enrolled CCA patients who underwent BS for detection of bone metastasis between January 2012 and July 2020. The BS images were reviewed by two nuclear medicine physicians to assess BS positivity. Factors including tumor location, T stage, regional lymph node metastasis, other distant metastases, and serum carbohydrate antigen 19-9 (CA19-9) were evaluated. Associations between covariates and positive BS were analyzed using bivariate and multiple logistic regressions. Results: Among 158 CCA patients, 70 (44.3%), 84 (53.2%), and 4 (2.5%) had positive, negative, and equivocal BS, respectively. Of all 70 positive cases, 50 cases (71.4%) had multiple metastatic lesions. The spine was the most common metastatic site (n=55, 78.6%). After exclusion of equivocal cases, 154 were included in the regression models. In bivariate logistic regression, the factors associated with BS positivity were intrahepatic tumor location (OR=2.18, p-value=0.039) and other distant metastasis (OR=2.08, p-value=0.028). Further analysis using multiple logistic regression showed only other distant metastasis was associated with positive BS (OR=2.66, p-value=0.008). Conclusion: There was a significant association between other distant metastasis and BS positivity in CCA patients. This factor should be considered as a clinical indication for requesting BS in this group of patients.

Prognostic Factors of Pretreatment Magnetic Resonance Imaging for Predicting Clinical Outcome in Patients With Parotid Gland Cancer.

This study aimed to assess the utility of pretreatment magnetic resonance imaging (MRI) in predicting the clinical outcomes of patients with parotid gland cancer. A total of 43 patients with histopathologically confirmed primary parotid gland cancer, who underwent pretreatment MRI, were enrolled in this study. All images were retrospectively reviewed, and MRI features were evaluated as possible prognostic factors influencing the progression-free survival (PFS) using the Kaplan-Meier method and Cox proportional hazards regression model. Cox regression analysis was used to estimate the hazard ratios (HRs) with 95% confidence interval (95% CI) values. Kaplan-Meier survival analysis showed that old age (>73 years, P < 0.01), large maximum tumor diameter (>33 mm, P < 0.01), low apparent diffusion coefficient value (≤1.29 ×10 -3 mm 2 /s, P < 0.01), ill-defined margin ( P < 0.01), skin invasion ( P < 0.01), regional nodal metastasis ( P < 0.01), heterogeneous enhancement ( P < 0.05), and high signal intensity ratio on gadolinium-enhanced fat-suppressed T1-weighted images (>2.017, P < 0.05) were significant predictors of worse PFS. Cox proportional hazards regression analysis revealed that regional nodal metastasis (HR, 32.02; 95% CI, 6.42-159.84; P < 0.01) and maximum tumor diameter (HR, 1.04; 95% CI, 1.01-1.08; P < 0.05) were independent predictors of PFS. Pretreatment MRI parameters could be prognostic factors of patients with parotid gland cancer. In particular, the maximum tumor diameter and regional nodal metastasis, which were closely associated with T and N classifications, were important prognostic factors in predicting the PFS.

WNT Pathway Mutations in Metachronous Oligometastatic Castration-Sensitive Prostate Cancer

WNT signaling is a cellular pathway that has been implicated in the development and progression of prostate cancer. Oligometastatic castration-sensitive prostate cancer (omCSPC) represents a unique state of disease in which metastasis-directed therapy (MDT) has demonstrated improvement in progression-free survival. Herein, we investigate the clinical implications of genomic alterations in the WNT signaling cascade in men with omCSPC. We performed an international multi-institutional retrospective study of 277 men with metachronous omCSPC who underwent targeted DNA sequencing of their primary/metastatic tumor. Patients were classified by presence or absence of pathogenic WNT pathway mutations (in the genes APC, RNF43, and CTNNB1). Pearson χ2 and Mann-Whitney U tests were used to determine differences in clinical factors between genomic strata. Kaplan-Meier survival curves were generated for radiographic progression-free survival and overall survival, stratified according to WNT pathway mutation status. A pathogenic WNT pathway mutation was detected in 11.2% of patients. Patients with WNT pathway mutations were more likely to have visceral metastases (22.6% vs 2.8%; P < .01) and less likely to have regional lymph node metastases (29.0% vs 50.4%; P = .02). At time of oligometastasis, these patients were treated with MDT alone (33.9%), MDT + limited course of systemic therapy (20.6%), systemic therapy alone (22.4%), or observation (defined as no treatment for ≥6 months after metastatic diagnosis). Multivariable cox regression demonstrated WNT pathway mutations associated with significantly worse overall survival (hazard ratio, 3.87; 95% confidence interval, 1.25-12.00). Somatic WNT pathway alterations are present in approximately 11% of patients with omCSPC and are associated with an increased likelihood of visceral metastases. Although these patients have a worse natural history, they may benefit from MDT.

The correlation between No. 6 and No. 14v lymph node metastasis and the value of dissecting these lymph nodes in radical gastrectomy

Radical gastrectomy with D2 lymphadenectomy has been widely performed as the standard surgery for patients with gastric cancer in major medical centers in China and abroad. However, the exact extent of lymph node dissection is still controversial. In the latest version of the Japanese Gastric Cancer Treatment Guidelines, No. 14v lymph nodes (along the root of the superior mesenteric vein) are again defined as loco-regional lymph nodes, and it is clarified that distal gastric cancer presenting with infra-pyloric regional lymph node (No.6) metastasis is recommended for D2+ superior mesenteric vein (No. 14v) lymph node dissection. To explore the relevance and clinical significance of No.6 and No.14v lymphadenectomy in radical gastric cancer surgery, a review of the national and international literature revealed that No.6 lymph node metastasis was associated with No.14v lymph node metastasis, that No.6 lymph node status was a valid predictor of No.14v lymph node negative status and false negative rate, and that for gastric cancer patients with No. 14v lymph node negative and No.6 lymph node positive, the dissection of No.14v lymph node may also have some significance. The addition of No. 14v lymph node dissection in radical gastrectomy is safe, but it is more important to distinguish the patients who can benefit from it. Professor Liang Han of Tianjin Medical University Cancer Hospital is currently leading a multicenter, large-sample, prospective clinical trial (NCT02272894) in China, which is expected to provide higher level evidence for the clinical significance of lymph node dissection in No.14v.

Interferon Alfa-2b Adjuvant Therapy of High-Risk Resected Cutaneous Melanoma: The Eastern Cooperative Oncology Group Trial EST 1684.

Interferon alfa-2b (IFN alpha-2b) exhibits antitumor activity in metastatic melanoma and on this basis has been evaluated as an adjuvant therapy following surgery for deep primary (T4) or regionally metastatic (N1) melanoma. A randomized controlled study of IFN alpha-2b (Schering-Plough, Kenilworth, NJ) administered at maximum-tolerated doses of 20 MU/m2/d intravenously (i.v.) for 1 month and 10 MU/m2 three times per week subcutaneously (SC) for 48 weeks versus observation, was conducted by the Eastern Cooperative Oncology Group (ECOG) in 287 patients. A significant prolongation of relapse-free survival (P = .0023, one-sided) and prolongation of overall survival (P = .0237, one-sided) was observed with IFN alpha-2b therapy in this trial, which is now mature with a median follow-up time of 6.9 years. The impact of treatment on relapse rate is most pronounced early during the treatment interval. The overall benefit of treatment in this trial was analyzed stratified by tumor burden and the presence or absence of microscopic nonpalpable and palpable regional lymph node metastasis. The benefit of therapy with IFN alpha-2b was greatest among node-positive strata. Toxicity of IFN alpha-2b required dose modification in the majority of patients, but treatment at > or = 80% of the scheduled dose was feasible in the majority of patients through the IV phase of treatment, and for more than 3 months of SC maintenance therapy. Discontinuation of treatment due to toxicity was infrequent after the fourth month of therapy. IFN alpha-2b prolongs the relapse-free interval and overall survival of high-risk resected melanoma patients. The increment in median disease-free survival (from 1 to 1.7 years) and overall survival (from 2.8 to 3.8 years) that results from this therapy is associated with a 42% improvement in the fraction of patients who are continuously disease-free after treatment with IFN (from 26% to 37%) in comparison to observation. IFN alpha-2b is the first agent to show a significant benefit in relapse-free and overall survival of high-risk melanoma patients in a randomized controlled trial.

Integrating Preoperative Computed Tomography and Clinical Factors for Lymph Node Metastasis Prediction in Esophageal Squamous Cell Carcinoma by Feature-Wise Attentional Graph Neural Network

This study aimed to propose a regional lymph node (LN) metastasis prediction model for patients with esophageal squamous cell carcinoma (ESCC) that can learn and adaptively integrate preoperative computed tomography (CT) image features and nonimaging clinical parameters. Contrast-enhanced CT scans taken 2 weeks before surgery and 20 clinical factors, including general, pathologic, hematological, and diagnostic information, were collected from 357 patients with ESCC between October 2013 and November 2018. There were 999 regional LNs (857 negative, 142 positive) with pathologically confirmed status after surgery. All LNs were randomly divided into a training set (n=738) and a validation set (n=261) for testing. The feature-wise attentional graph neural network (FAGNN) was composed of (1) deep image feature extraction by the encoder of 3-dimensional UNet and high-level nonimaging factor representation by the clinical parameter encoder; (2) a feature-wise attention module for feature embedding with learnable adaptive weights; and (3) a graph attention layer to integrate the embedded features for final LN level metastasis prediction. Among the 4 models we constructed, FAGNN using both CT and clinical parameters as input is the model with the best performance, and the area under the curve (AUC) reaches 0.872, which is better than manual CT diagnosis method, multivariable model using CT only (AUC=0.797), multivariable model with combined CT and clinical parameters (AUC=0.846), and our FAGNN using CT only (AUC=0.853). Our adaptive integration model improved the metastatic LN prediction performance based on CT and clinical parameters. Our model has the potential to foster effective fusion of multisourced parameters and to support early prognosis and personalized surgery or radiation therapy planning in patients with ESCC.

Overexpression of the NEK9–EG5 axis is a novel metastatic marker in pathologic stage T3 colon cancer

NEK9 is a key player in the NEK9–EG5 axis for microtubule polymerization, chromosome alignment, and mitosis. In present study, we investigated the altered expression of the NEK9, EG5 and acetyl-α-tubulin as well as common epithelial–mesenchymal transition (EMT) markers (E-cadherin, vimentin, claudin-1, and β-catenin) through the immunohistochemistry analysis of 138 patients with pathologic T3 (pT3) stage colon cancers, and evaluated their metastatic potential. NEK9 expression showed an association with distant metastasis (P = 0.032) and was an independent predictive factor for distant metastasis (HR = 3.365, P < 0.001) by multivariate analysis, which was more significant than either the regional nodal metastasis (HR = 2.496, P = 0.007) or lymphovascular invasion (HR = 2.090, P = 0.153). Positive correlations were observed between NEK9 and EG5 or acetyl-α-tubulin (r = 0.236 and P = 0.007; r = 0.181 and P = 0.038, respectively) and concordant overexpression of the NEK9–EG5 axis was further confirmed in colon cancer cell lines. These findings collectively suggest that the overexpression of the NEK9–EG5 axis is present and associated with distant metastasis in colon cancer. These biomarkers might be useful for predicting metastatic potential among the patients with pT3 colon cancers.

Investigating the functional role of SETD6 in lung adenocarcinoma

BackgroundSET domain containing 6 (SETD6) has been shown to be upregulated in multiple human cancers and can promote malignant cell survival. However, expression and function of SETD6 in lung adenocarcinoma (LUAD) remains unaddressed. This study aimed to demonstrate the expression pattern, biological roles and potential mechanisms by which SETD6 dysregulation is associated with LUAD.MethodsThe expression level of SETD6 was evaluated in LUAD clinical specimens and its correlation with clinical parameters were analyzed. In vitro, gain-of-function and loss-of-function experiments were performed to evaluate the effects of SETD6 on cell proliferation, apoptosis, migration, and colony formation of LUAD cell line A549. Western-blot was performed to investigate the involvement of nuclear factor-κB (NF-κB) and nuclear factor erythroid 2–related factor 2 (Nrf2) pathways as downstream signaling of SETD6 in LUAD cells.ResultsCompared with non-tumorous tissues, SETD6 was overexpressed in tumor tissues, and its overexpression significantly correlates with higher rates of regional lymph node metastasis and poor prognosis in patients with LUAD. In A549 cell line, SETD6 overexpression could promote cell proliferation, migration, colony formation and inhibit cell apoptosis, whereas SETD6 knockdown caused the opposite effects. Furthermore, we demonstrated that the mechanisms underlying the effect of SETD6 on LUAD biological behaviors may be through its interaction with NF-κB and Nrf2 signaling pathways.ConclusionsSETD6, which is highly expressed in LUAD tumor tissues, plays an important role in promoting the malignant behaviors of LUAD via likely the NF-κB and Nrf2 signaling pathways.

Worst pattern of invasion and other histopathological features in oral cancer as determinants of prognosis and survival rate: A retrospective cohort analysis.

Oral cavity squamous cell carcinoma (OCSCC) is a well-recognized malignancy of the head and neck. Studies on patients with early-stage oral cancer have shown that they develop locally recurring and/or regional lymph node metastasis, which results in disease-associated mortality. Thus, early-stage oral cancer does not always present good prognoses. The present study aimed to determine the efficacy of using worst pattern of invasion (WPOI) and other histopathological features, such as prognostic factors in OCSCC, and analyze the impact of resection margin status and histopathological prognostic indicators on local recurrence (LR) and overall survival (OS) in patients with OCSCC. A retrospective cohort study was conducted by reviewing the charts of 63 patients with OCSCC treated with primary surgery at King Abdulaziz University Hospital between 2012 and 2019. An author and an experienced pathologist reviewed pathology slides. Associations of histopathological factors, including differentiation, stage, lymphovascular invasion, extracapsular extension, perineural invasion (PNI), WPOI and surgical margins, with LR or disease-free survival (DFS) were evaluated. Univariate analysis identified WPOI and PNI, and multivariate analysis identified the WPOI as predictive factors for LR and DFS. Kaplan-Meier analysis identified the WPOI and PNI as predictive factors for OS and WPOI as a predictive factor for DFS. Therefore, it may be concluded that WPOI and PNI are significant independent prognostic factors for local tumor control and DFS in patients with OCSCC.

Prostate-specific Membrane Antigen–radioguided Surgery Facilitates Pelvic Lymph Node Dissection During Radical Prostatectomy for the Treatment of Locally Advanced Prostate Cancer with Regional Lymph Node Metastases

Lymph node metastases (LNMs) are common in intermediate- to high-risk prostate cancer (PC) and may be missed during extended pelvic lymph node dissection (ePLND). Here we report on the use of prostate-specific membrane antigen (PSMA)-radioguided surgery (RGS) during open radical prostatectomy (RP) with ePLND to resect locoregional LNMs identified on preoperative PSMA positron emission tomography (PET). Preoperative PSMA PET showed 78 LNMs in 35 patients undergoing RP with ePLND and RGS between January 2018 and June 2020. In 14 patients (40%), LNMs were located outside the ePLND template. RGS achieved resection of PSMA-positive LNMs in 33/35 patients (94%). On univariable analysis, lower metastatic burden with up to two PSMA-positive LNMs on preoperative PET was associated with better postoperative outcomes. Limitations include the retrospective analysis and the small sample size. RGS facilitates resection of PSMA-positive LNs in patients treated with RP. Our data indicate a favorable treatment outcome in patients with low metastatic LN burden on preoperative PSMA PET. Patient summaryWe investigated the use of radioactive guidance to remove lymph nodes affected by prostate cancer during surgical removal of the prostate. This approach can help to identify cancerous lymph nodes that might otherwise be missed and could lead to better survival outcomes.

Interobserver agreement in the histopathological classification of desmoplastic melanomas

Desmoplastic melanoma is a subtype of melanoma characterised by amelanotic fusiform melanocytes dispersed in a collagenous stroma. Cell-poor and fibrous stroma-rich 'pure' variants have been distinguished from 'mixed' variants with areas of higher cell density and/or less desmoplastic stroma. This distinction is relevant because patients whose tumours display a pure phenotype have a lower risk for regional lymph node metastasis and distant recurrence. However, little is known about interobserver agreement among pathologists in the subclassification of desmoplastic melanoma. To address this issue, we conducted a study in which eleven dermatopathologists independently evaluated whole slide scanned images of excisions from 30 desmoplastic melanomas. The participating pathologists were asked to classify the tumours as pure or mixed. They were also asked to record the presence or absence of neurotropism and angiotropism. We found substantial interobserver agreement between the 11 dermatopathologists in the classification of tumours as pure versus mixed desmoplastic melanoma (kappa=0.64; p<0.0001). There was fair agreement between the 11 dermatopathologists in the evaluation of presence versus absence of neurotropism (kappa=0.26; p<0.0001), and slight agreement in the assessment of angiotropism (kappa=0.13; p<0.0001). The level of concordance in the subclassification of desmoplastic melanomas is encouraging for the acceptance of this prognostic parameter in the real-world practice of melanoma pathology.

THE VALUE OF THE EXPRESSION OF K-RAS AND DNA-STATUS IN THE PROGRESSION OF ENDOMETRIOID ENDOMETRIAL CARCINOMA IN PATIENTS WITH EARLY STAGES OF TUMOR PROCESS

Summary. Aim: evaluation of DNA ploidy and K-RAS oncoprotein expression in endometrioid endometrial carcinoma (EEC) to determine the metastatic potential of patients with an initial stage of the malignant process. Objects and methods: the study was conducted on samples of postoperative material of 54 patients with EEC stage I according to FIGO (average age: 60.4 years; part from 38 to 72 years). Clinical, morphological, immunohistochemical, flow cytometry, and statistical methods were used for the research. Results: retrospective analysis of medical history revealed patients with EEC who developed metastases in regional lymph nodes within 1.8– 36.6 months. On the basis of this, two groups of studies were formed: I — EEC of patients without metastases (n = 34), II — patients with metastases (n = 20). As a result of the evaluation of the clinical and pathological features of EEC, it was established that G1–G2 tumors predominated (79.4%) in patients of the I group, and in 70.6% of cases, not deep invasion of the myometrium was detected. 55.0% of EEC of the II group had a low degree of differentiation with the deep invasion of the myometrium, which was correlated with a high expression of the oncoprotein K-RAS and the proliferation index. Aneuploidy with iDNA ≥ 2.0 was observed in 20.0% of EEC II group. In such regions, a probably higher expression of K-RAS was determined with this indicator in diploid carcinomas of this group. In addition, the term of occurrence of metastases in patients with aneuploidy was probably shorter than in patients of this group with diploid statuses. Conclusions: it was established that the expression of the K-RAS oncoprotein and DNA ploidy in EEC are associated with the course of the tumor process in stage I patients, which makes it possible to verify patients with a high risk of metastasis.

UNCOMMON SALIVARY GLAND TUMORS: A CASE SERIES

Salivary gland tumors are one of the rare entities having the annual incidence rate of 0.5 to 2 per 100,000 persons[7]. Majority of them are benign, only 20% cases are malignant. They usually present as painless mass in the oral cavity or close to their anatomical location. The main challenge is to differentiate between the benign and the malignant ones. Thus, various imaging modalities are used. Investigations such as ne needle aspiration cytology and MRI scans provide some useful information, but most cases will require tissue diagnosis to come to a denitive conclusion. Hence, biopsy or histopathological study of the surgically excised tissue is the gold standard for diagnosis. Benign tumour and early low-grade malignancies can be adequately treated with surgery alone, while more advanced and high-grade tumour with regional lymph node metastasis will require postoperative radiotherapy[11]. The role of chemotherapy remains largely palliative. In this article, we have presented a series of cases with uncommon tumors involving the various salivary glands.

A specimen out of the blue, case of squamous cell carcinoma demonstrating various patterns of perineural Invasion

Oral squamous cell carcinoma (OSCC) is the fifth most frequent cancer in the world and about 3% of all malignant neoplasms are usually spread by lymphatic or rarely hematogenous spread. Perineural invasion (PNI) is an alternate method of tumor spread and an important prognostic factor for further treatment plans in OSCC. The patterns of PNI are categorized, according to various research articles and studies conducted, some of the common ones are complete encirclement, incomplete “crescent-like” encirclement, sandwiching, onion skin, partial invasion, and neural permeation. We received a hemiglossectomy specimen of a 62-year-old male diagnosed with squamous cell carcinoma (SCC) on a small biopsy with an ulceroproliferative lesion in the left lateral border of tongue. Microscopy showed an invasive tumor showing features of well-differentiated SCC with extensive various patterns of PNI such as complete encirclement, incomplete encirclement, sandwich pattern, onion skinning, crescenting and neural permeation. PNI indicates and predicts the local recurrence and also regional nodal metastasis in patients with OSCC. PNI should be searched and included in the histopathology report in every OSCC case including recurrent cases.

The sealing effect of magnetic-sealing uterine manipulator in isolated uterus from patients with early-stage cervical cancer: a pre-clinical study.

Traditional uterine manipulator is considered as the main reason for short survival of patients with early-stage cervical cancer during minimally invasive surgery. This study aims to assess the sealing effect of magnetic-sealing uterine manipulators (MUMs) in isolated uteruses. The study was performed on isolated uterus from patients with early-stage cervical cancer who underwent open abdominal radical hysterectomy between November 2019 to April 2021. Right-angle forceps closure tests (groups 1 and 3) were defined as control tests. One experimental MUM closure test (group 2) and 2 control tests were respectively carried out in each of the isolated uterus. DNA ploidy analysis system was used to observe exfoliated cells. Statistical analysis was performed using Wilcoxon signed-rank test to assess the sealing effect of MUM. We identified 36 patients. No regional node metastasis was discovered and only one tumor was larger than 4.0 cm in diameter. The mean of exfoliated tumor cells in groups 1, 2, and 3 were 1, 1, and 2, respectively. There was no significant difference in the quantity of exfoliated cells between groups 1 and 3 (p=0.476), so the results of the 2 groups were merged. Subsequently, a significant difference was observed between combined right-angle forceps closure tests and MUM closure tests (p=0.022). The sealing effect of MUM was better than that of right-angle forceps. MUM can effectively seal cervical cancer cells in the cup cover, avoiding the dissemination of tumor cells. Chinese Clinical Trial Register Identifier: ChiCTR1900026012.

Metastatic retinoblastoma at presentation: Clinical presentation, treatment, and outcomes.

The aim of this study was to retrospectively determine clinical features, treatment outcomes, and overall survival in four patients with metastatic retinoblastoma at presentation. The mean age at diagnosis was 63 months (range: 24-108 months). Three patients had overt orbital disease of at least one eye and one patient had microscopic orbital disease with scleral infiltration on histopathology. Metastatic sites included regional lymph nodes (RLN) (n = 4), bone marrow (BM) (n = 2), and cerebrospinal fluid (CSF) (n = 1). The most common sites of RLN were ipsilateral preauricular nodes (two patients) and contralateral parotid gland involvement (one patient). The treatment administered included primary enucleation (n = 1), high-dose intravenous chemotherapy (n = 4), secondary enucleation (n = 2), orbital external beam radiotherapy (n = 3), and intrathecal chemotherapy (n = 1). High-risk features included massive choroidal and microscopic scleral infiltration in the eye that underwent primary enucleation. At a mean follow-up of 33 months (range, 4-68 months), one patient with CSF involvement deceased in 4 months. The remaining three patients were alive and disease-free at the last mean follow-up period of 43 months (range, 18-68 months). The results of our study showed that RLN and BM metastasis respond well to treatment while CSF metastasis is associated with poor prognosis.

Analysis of Risk Factors for Distant Metastasis of Pancreatic Ductal Adenocarcinoma without Regional Lymph Node Metastasis and a Nomogram Prediction Model for Survival.

Negative regional lymph nodes do not indicate a lack of distant metastasis. A considerable number of patients with negative regional lymph node pancreatic cancer will skip the step of regional lymph node metastasis and directly develop distant metastasis. We retrospectively analyzed the clinicopathological characteristics of patients with negative regional lymph node pancreatic cancer and distant metastasis in the Surveillance, Epidemiology, and End Results database from 2010 to 2015. Multivariate logistic analysis and Cox analysis were used to determine the independent risk factors that promoted distant metastasis and the 1-, 2-, and 3-year cancer-specific survival in this subgroup. Sex, age, pathological grade, surgery, radiotherapy, race, tumor location, and tumor size were significantly correlated with distant metastasis (P < 0.05). Among these factors, pathological grade II and above, tumor site other than the pancreatic head, and tumor size >40 mm were independent risk factors for distant metastasis; age ≥60 years, tumor size ≤21 mm, surgery, and radiation were protective factors against distant metastasis. Age, pathological grade, surgery, chemotherapy, and metastasis site were identified as predictors of survival. Among them, age ≥40 years, pathological grade II and above, and multiple distant metastasis were considered independent risk factors for cancer-specific survival. Surgery and chemotherapy were considered protective factors for cancer-specific survival. The prediction performance of the nomogram was significantly better than that of the traditional American Joint Committee on Cancer tumor, node, metastasis staging system. We also established an online dynamic nomogram calculator, which can predict the survival rate of patients at different follow-up time points. Pathological grade, tumor location, and tumor size were independent risk factors for distant metastasis in pancreatic ductal adenocarcinoma with negative regional lymph nodes. Older age, smaller tumor size, surgery, and radiotherapy were protective factors against distant metastasis. A new nomogram that was constructed could effectively predict cancer-specific survival in pancreatic ductal adenocarcinoma with negative regional lymph nodes and distant metastasis. Furthermore, an online dynamic nomogram calculator was established.

A nomogram based on dual-layer detector spectral computed tomography quantitative parameters and morphological quantitative indicator for distinguishing metastatic and nonmetastatic regional lymph nodes in pancreatic ductal adenocarcinoma.

There is no unified scope for regional lymph node (LN) dissection in patients with pancreatic ductal adenocarcinoma (PDAC). Incomplete regional LN dissection can lead to postoperative recurrence, while blind expansion of the scope of regional LN dissection significantly increases the perioperative risk without significantly prolonging overall survival. We aimed to establish a noninvasive visualization tool based on dual-layer detector spectral computed tomography (DLCT) to predict the probability of regional LN metastasis in patients with PDAC. A total of 163 regional LNs were reviewed and divided into a metastatic cohort (n=58 LNs) and nonmetastatic cohort (n=105 LNs). The DLCT quantitative parameters and the nodal ratio of the longest axis to the shortest axis (L/S) of the regional LNs were compared between the two cohorts. The DLCT quantitative parameters included the iodine concentration in the arterial phase (APIC), normalized iodine concentration in the arterial phase (APNIC), effective atomic number in the arterial phase (APZeff), normalized effective atomic number in the arterial phase (APNZeff), slope of the spectral attenuation curves in the arterial phase (APλHU), iodine concentration in the portal venous phase (PVPIC), normalized iodine concentration in the portal venous phase (PVPNIC), effective atomic number in the portal venous phase (PVPZeff), normalized effective atomic number in the portal venous phase (PVPNZeff), and slope of the spectral attenuation curves in the portal venous phase (PVPλHU). Logistic regression analysis based on area under the curve (AUC) was used to analyze the diagnostic performance of significant DLCT quantitative parameters, L/S, and the models combining significant DLCT quantitative parameters and L/S. A nomogram based on the models with highest diagnostic performance was developed as a predictor. The goodness of fit and clinical applicability of the nomogram were assessed through calibration curve and decision curve analysis (DCA). The combined model of APNIC + L/S (APNIC + L/S) had the highest diagnostic performance among all models, yielding an AUC, sensitivity, and specificity of 0.878 [95% confidence interval (CI): 0.825-0.931], 0.707, and 0.886, respectively. The calibration curve indicated that the APNIC-L/S nomogram had good agreement between the predicted probability and the actual probability. Meanwhile, the decision curve indicated that the APNIC-L/S nomogram could produce a greater net benefit than could the all- or-no-intervention strategy, with threshold probabilities ranging from 0.0 to 0.75. As a valid and visual noninvasive prediction tool, the APNIC-L/S nomogram demonstrated favorable predictive efficacy for identifying metastatic LNs in patients with PDAC.