Prediction of Microvascular Invasion and Its M2 Classification in Hepatocellular Carcinoma Based on Nomogram Analyses

Background and AimsAs a key pathological factor, microvascular invasion (MVI), especially its M2 grade, greatly affects the prognosis of liver cancer patients. Accurate preoperative prediction of MVI and its M2 classification can help clinicians to make the best treatment decision. Therefore, we aimed to establish effective nomograms to predict MVI and its M2 grade.MethodsA total of 111 patients who underwent radical resection of hepatocellular carcinoma (HCC) from January 2015 to September 2020 were retrospectively collected. We utilized logistic regression and least absolute shrinkage and selection operator (LASSO) regression to identify the independent predictive factors of MVI and its M2 classification. Integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were calculated to select the potential predictive factors from the results of LASSO and logistic regression. Nomograms for predicting MVI and its M2 grade were then developed by incorporating these factors. Area under the curve (AUC), calibration curve, and decision curve analysis (DCA) were respectively used to evaluate the efficacy, accuracy, and clinical utility of the nomograms.ResultsCombined with the results of LASSO regression, logistic regression, and IDI and NRI analyses, we founded that clinical tumor-node-metastasis (TNM) stage, tumor size, Edmondson–Steiner classification, α-fetoprotein (AFP), tumor capsule, tumor margin, and tumor number were independent risk factors for MVI. Among the MVI-positive patients, only clinical TNM stage, tumor capsule, tumor margin, and tumor number were highly correlated with M2 grade. The nomograms established by incorporating the above variables had a good performance in predicting MVI (AUCMVI = 0.926) and its M2 classification (AUCM2 = 0.803). The calibration curve confirmed that predictions and actual observations were in good agreement. Significant clinical utility of our nomograms was demonstrated by DCA.ConclusionsThe nomograms of this study make it possible to do individualized predictions of MVI and its M2 classification, which may help us select an appropriate treatment plan.

Reinvestigating Tumor–Ventricle Relationship of Craniopharyngiomas With Predominantly Ventricular Involvement: An Endoscopic Endonasal Series Based on Histopathological Assessment

ObjectiveCraniopharyngiomas (CPs) predominantly involving the third ventricle were commonly termed “intraventricular” lesions. The aim of this study was to clarify the anatomical relationship between the tumor and the third ventricle by both surgical and histological investigation.MethodsA retrospective review of primarily resected CPs by endoscopic endonasal surgery was performed. CPs with predominantly ventricular involvement were selected for study inclusion by preoperative imaging. The surgical procedure of each case was reviewed. The wholly removed tumor specimens were histologically analyzed, in all cases, to investigate the tumor–third ventricle relationship using hematoxylin and eosin, immunochemical, and immunofluorescence staining.ResultsTwenty-six primary CPs predominantly involving the third ventricle were selected from our series of 223 CPs treated by endoscopic endonasal surgery between January 2017 and March 2021. Gross-total resection was achieved in 24 (92.3%) of 26 patients, with achievement of near-total resection in the remaining patients. A circumferential layer of stretched third ventricle floor was identified surrounding the tumor capsule, which could be peeled off easily from the ventricle floor remnants at most areas of the plane of tumor attachment. Some portions of the tumor capsule tightly adhered to the third ventricle floor were removed together with the floor. A breach of various size was observed at the third ventricle floor after tumor removal in most cases, the floor remaining intact in only two cases (7.7%). Histological examination on marked portions of tumor capsule showed that the pia mater was frequently detected at most of the tumor–brain interface, except at the antero-frontal border of tumor contacting with the third ventricle floor. At this point, a layer of gliosis with various thickness was observed between the tumor and the neural tissue of the third ventricle floor.ConclusionCPs with predominantly ventricular involvement should be considered as lesions with an extraventricular, epi-pia topography rather than “intraventricular” or “subpial” topography. Accurate understanding of the relationship between the third ventricle and such tumors would predict the circumferential cleavage plane of dissection, and remind neurosurgeons of performing dissection along the safe surgical plane to achieve total tumoral resection with minimizing hypothalamic damage.

Development and Validation of Prognostic Nomograms Predicting Recurrence and Survival in Patients with Solitary Hepatocellular Carcinoma Following Curative Liver Resection

Background: This work was designed to establish and verify our nomograms integrating clinicopathological characteristics with hematological biomarkers to predict both disease-free survival (DFS) and overall survival (OS) in solitary hepatocellular carcinoma (HCC) patients following hepatectomy.Methods: We scrutinized the data retrospectively from 414 patients with a clinicopathological diagnosis of solitary HCC from Guangxi Medical University Cancer Hospital (Nanning, China) between January 2004 and December 2012. Following the random separation of the samples in a 7:3 ratio into the training set and validation set, the former set was assessed by Cox regression analysis to develop two nomograms to predict the 1-year and 3-year DFS and OS (3-years and 5-years). This was followed by discrimination and calibration estimation employing Harrell’s C-index (C-index) and calibration curves, while the internal validation was also assessed.Results: In the training cohort, the tumor diameter, tumor capsule, macrovascular invasion, and alpha-fetoprotein (AFP) were included in the DFS nomogram. Age, tumor diameter, tumor capsule, macrovascular invasion, microvascular invasion, and aspartate aminotransferase (AST) were included in the OS nomogram. The C-index was 0.691 (95% CI: 0.644-0.738) for the DFS-nomogram and 0.713 (95% CI: 0.670-0.756) for the OS-nomogram. The survival probability calibration curves displayed a fine agreement between the predicted and observed ranges in both data sets. Conclusion: Our nomograms combined clinicopathological features with hematological biomarkers to emerge effective in predicting the DFS and OS in solitary HCC patients following curative liver resection. Therefore, the potential utility of our nomograms for guiding individualized treatment clinically and monitor the recurrence monitoring in these patients.

Development and validation of prognostic nomograms in patients with hepatocellular carcinoma: a population-based study

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. The existing staging system has a limited budget capacity for HCC recurrence. The authors aimed to establish and verify two nomogram models to predict disease-free survival (DFS) and overall survival (OS) in patients with HCC. Methods: Patients diagnosed with HCC between August 2011 and March 2016 were recruited. Data were randomly divided into a training cohort and a validation cohort. Based on univariate and multivariate Cox regression analysis, independent risk factors for DFS and OS were identified, and two nomogram models were established to predict patient survival. Results: Sex, tumor size, Barcelona Clinic Liver Cancer (BCLC) stage, tumor capsule, macrovascular invasion, AST-to-platelet ratio index, AST-to-lymphocyte ratio index, neutrophil–lymphocyte ratio and alpha-fetoprotein (AFP) were used to build the nomogram for DFS, while age, tumor size, BCLC stage, tumor capsule, macrovascular invasion, systemic immune-inflammation index, AST, total bilirubin and AFP were used to build the nomogram for OS. Calibration curves showed good agreement between the nomogram prediction and actual observation. C-indices in both nomograms were significantly higher than BCLC. Conclusion: The two nomograms improved the accuracy of individualized prediction of DFS and OS, which may help doctors screen patients with a high risk of recurrence to formulate individualized treatment plans.

Dorsal displacement of the facial nerve in vestibular schwannoma surgery

The course of the facial nerve (FN) has been extensively investigated in patients with vestibular schwannomas (VSs). FN running dorsally to the tumor capsule accounts for less than 3% of the cases. Diffusion tensor imaging (DTI)–based fiber tracking helps to preoperatively identify the FN. During surgery, a higher risk of injury is associated with the dorsal location of the FN. The authors demonstrate the nuances and tricks to identify and preserve a dorsal displaced FN during resection of a large VS, T3b according to the Hannover classification, through the retrosigmoid-transmeatal approach. The video can be found here: https://stream.cadmore.media/r10.3171/2021.7.FOCVID2182

Case Report: A Case Series Using Natural Anatomical Gaps—Posterior Cervical Approach to Skull Base and Upper Craniocervical Meningiomas Without Bone Removal

Background: Removal of anteriorly located tumors of the upper cervical spine and craniovertebral junction (CVJ) is a particular surgical challenge. Extensive approaches are associated with pain, restricted mobility of neck and head and, in case of foramen magnum and clivus tumors, with retraction of brainstem and cerebellum.Methods: Four symptomatic patients underwent resection of anteriorly located upper cervical and lower clivus meningiomas without laminotomy or craniotomy using a minimally invasive posterior approach. Distances of natural gaps between C0/C1, C1/C2, and C2/C3 were measured using preoperative CT scans and intraoperative lateral x-rays.Results: In all patients, safe and complete resection was conducted by the opening of the dura between C0/C1, C1/C2, and C2/C3, respectively. There were no surgical complications. Local pain was reported as very moderate by all patients and postoperative recovery was extremely fast. All tumors had a rather soft consistency, allowing mass reduction prior to removal of the tumor capsule and were well separable from lower cranial nerves and vascular structures.Conclusion: If tumor consistency is appropriate for careful mass reduction before removal of the tumor capsule and if tumor margins are not firmly attached to crucial structures, then upper cervical, foramen magnum, and lower clivus meningiomas can be safely and completely removed through natural gaps in the CVJ region. Both prerequisites usually become clear early during surgery. Thus, this tumor entity may be planned using this minimally invasive approach and may be extended if tumor consistency turns out to be less unfavorable for resection or if crucial structures cannot be easily separated from the tumor.

Sub-Classification of Cirrhosis Affects Surgical Outcomes for Early Hepatocellular Carcinoma Independent of Portal Hypertension

Severity of liver cirrhosis is distinct from clinical portal hypertension because there exist different degrees of liver cirrhosis in hepatocellular carcinoma (HCC) patients without significant clinical portal hypertension. Whether severity of cirrhosis affects surgical outcomes for HCC patients in absence of portal hypertension or not remains unclear. This study aims to analyze the effect of cirrhotic severity on surgical outcomes for HCC patients with hepatitis B virus (HBV) infection in absence of portal hypertension. This retrospective study enrolled 166 patients who underwent curative resection for a single HCC ≤5 cm in absence of portal hypertension between February 2011 and December 2013. Liver cirrhosis was sub-classified into no/mild (no/F4A) and moderate/severe (F4B/F4C) according to the Laennec scoring system. The surgical outcomes and complications were analyzed. The surgical mortality was zero in this study. Major complications were apparently higher in the F4B/F4C group than in the no/F4A group (17.0% vs 7.4%, p <0.001). The 1-year, 3-year and 5-year overall survival (OS) rates were 98.5, 88.1 and 80%, respectively, in the no/F4A group, which were significantly higher than those in the F4B/F4C group (98.0, 69.2 and 54.7%, p = 0.001). Microscopic vascular invasion, absence of tumor capsule and severity of liver cirrhosis were independent risk factors of surgical outcomes for HCC patients without portal hypertension. In conclusion, severity of liver cirrhosis affected surgical outcomes for early-stage HCC patients independent of portal hypertension.

Infiltration of Immune Competent Cells into Primary Tumors and Their Surrounding Connective Tissues in Xenograft and Syngeneic Mouse Models

To fight cancer more efficiently with cell-based immunotherapy, more information about the cells of the immune system and their interaction with cancer cells in vivo is needed. Therefore paraffin wax embedded primary breast cancers from the syngeneic mouse WAP-T model and from xenografted tumors of breast, colon, melanoma, ovarian, neuroblastoma, pancreatic, prostate, and small cell lung cancer were investigated for the infiltration of immunocompetent cells by immunohistochemistry using antibodies against leukocyte markers. The following markers were used: CD45 as a pan-leukocyte marker, BSA-I as a dendritic cell marker, CD11b as an NK cell marker, and CD68 as a marker for macrophages. The labeled immune cells were attributed to the following locations: adjacent adipose tissue, tumor capsule, intra-tumoral septae, and cancer cells directly. In xenograft tumors, the highest score of CD45 and CD11b positive, NK, and dendritic cells were found in the adjacent adipose tissue, followed by lesser infiltration directly located at the cancer cells themselves. The detected numbers of CD45 positive cells differed between the tumor entities: few infiltrating cells in breast cancer, small cell lung cancer, neuroblastoma, a moderate infiltration in colon cancer, melanoma and ovarian cancer, strongest infiltration in prostate and pancreatic cancer. In the syngeneic tumors, the highest score of CD45 and CD11b positive, NK and dendritic cells were observed in the tumor capsule, followed by a lesser infiltration of the cancer tissue. Our findings argue for paying more attention to investigate how immune-competent cells can reach the tumor cells directly.