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.

Single-Fiber Diffuse Reflectance Spectroscopy and Spatial Frequency Domain Imaging in Surgery Guidance: A Study on Optical Phantoms

Diffuse reflectance spectroscopy (DRS) and imaging are increasingly being used in surgical guidance for tumor margin detection during endoscopic operations. However, the accuracy of the boundary detection with optical techniques may depend on the acquisition parameters, and its evaluation is in high demand. In this work, using optical phantoms with homogeneous and heterogeneous distribution of chromophores mimicking normal and pathological bladder tissues, the accuracy of tumor margin detection using single-fiber diffuse reflectance spectroscopy and spatial frequency domain imaging was evaluated. We also showed how the diffuse reflectance response obtained at different spatial frequencies with the spatial frequency domain imaging technique could be used not only to quantitatively map absorption and scattering coefficients of normal tissues and tumor-like heterogeneities but also to estimate the tumor depth localization. The demonstrated results could be helpful for proper analysis of the DRS data measured in vivo and for translation of optical techniques for tumor margin detection to clinics.

Epithelial–Mesenchymal Transition Phenotype and Peritumoral Immune Cell Infiltration in Advanced Biliary Tract Cancer

We evaluated the clinical implications of epithelial–mesenchymal transition (EMT) markers and peritumoral immune cell infiltration in patients with biliary tract cancer (BTC) treated with gemcitabine plus cisplatin (GemCis). Forty-five patients with advanced BTC who received GemCis were included as the study population. We conducted multiplex immunohistochemistry and examined EMT markers and their correlations with immune cell infiltrate at the invasive tumor margin. Study population was subdivided into two groups: twenty-four patients with short-term survival (SS) and 21 with long-term survival (LS). The density of tumor cells expressing epithelial marker E-cadherin (E-cadherin+ CK+) at the invasive tumor margin tended to be higher in the LS group than in the SS group (p = 0.065). The density of tumor cells expressing mesenchymal marker vimentin (vimentin+ CK+) was significantly higher in the SS group than in the LS group (p = 0.021). Accordingly, the density of E-cadherin− vimentin+ CK+ cells was also significantly higher in the SS group (p = 0.020). The density of vimentin+ CK+ cells was positively correlated with FoxP3+ CD4+ regulatory T-cells (r = 0.29, p = 0.047). EMT-related features were enriched in BTC patients with poor survival outcomes and were associated with the immunosuppressive tumor microenvironment.

Outcomes and Prognostic Factors in Patients with Malignant Peripheral Nerve Sheath Tumor

Objective: To investigate and report the clinical profiles, treatment patterns, and oncologic outcomes in MPNST patients, and to identify the prognostic factors that significantly affect survival.Materials and Methods: Patients diagnosed with and treated for histologically confirmed MPNST at our institute during the January 1997 to June 2018 study period were included. Patient medical records and surgical specimens were reviewed, and study-related data was extracted and analyzed.Results: There were 27 males and 32 females with a mean age of 44 years. Most patients presented with mass and most patients were AJCC stage III. Twenty-nine percent of patients had MPNST that was associated with NF-1. At a median follow-up time, 18 patients (30.51%) suffered from local disease recurrence. Two-year and 5-year overall survival was 72% and 46%, respectively. In univariate analysis, chemotherapy treatment and positive tumor margin were adverse prognostic factors for disease-free survival. In multivariate analysis, chemotherapy treatment (hazard ratio (HR): 3.415, 95% CI: 1.367-16.021; p=0.013) and positive tumor margin (HR: 4.680, 95% CI 1.828-10.314; p=0.014) were found to be independent prognostic factors for disease-free.Conclusion: Chemotherapy treatment and positive tumor margin were identified as independent adverse prognostic factors for disease-free and overall survival, respectively. Accordingly, early detection and appropriate treatment are essential for improved patient outcome.

Holmium laser-assisted laparoscopic partial cystectomy for bladder cancer: technical feasibility and outcome

BackgroundIn selected patients with bladder cancer, partial cystectomy is an alternative treatment for bladder preservation with fair oncologic result. During partial cystectomy, tumor margin demarcation is difficult. Various methods were introduced, however, there is no standard for tumor margin demarcation. We aimed to introduce and provide our experience with holmium laser-assisted method with ten patients.MethodsFrom March 2016 and February 2019, patients who want partial cystectomy for bladder cancer were enrolled in this study. Inclusion criteria were stage T2 or T3 disease and tumor location restricted within the dome, and lateral, posterior side of the bladder were included. Transurethral holmium laser-assisted mucosal incision was made and deepened until perivesical fat. Minimal Safety margin for 5–10 mm were spared, and tumor removal was done laparoscopically.ResultsTen patients underwent holmium laser-assisted laparoscopic partial cystectomy. All procedures were done without complication. The tumor locations were laterally in seven patients, dome in two patients, and posterior wall in one patient. Pathologic examination of surgical margin showed no cancer cell involvement in all cases. There were no recurrences or metastases for 12 months follow up.ConclusionsHolmium laser-assisted laparoscopic partial cystectomy is effective and safe technique. To achieve precise and appropriate surgical margin during the laparoscopic partial cystectomy, holmium laser resection provides feasible and safe method that assists in bladder incision with minimal ureteral orifice involvement.Trial registrationRetrospectively registered.

Evaluation of intestinal cancer by 1H HR-MAS NMR spectroscopy: A new diagnostic tool?

Previous studies have demonstrated that cancer cells harbor unique metabolic characteristics relative to healthy counterparts. The current study is a prospective ex-vivo HR-MAS NMR analysis of malignant colorectal cancer (CRC) tissue specimens and its corresponding benign tissues.To assess the HR-MAS Spectroscope qualitatively & to analyze significant difference between the normal, benign and malignant intestinal mucosa.Between November 2013and January 2016, 36 consecutive patients with confirmed CRC were recruited to a prospective observational study. Fresh tissue samples were obtained from center of tumor and 5 cm from tumor margin from surgical resection specimens. Samples were run in duplicate where tissue volume permitted to compensate for anticipated sample heterogeneity. Typically, the sample was packed into a 4 mm ZrO2 rotor of 50 μl capacity; a volume of 20μl of D2O having 0.03% TSP was used as a chemical shift reference. The sample-rotor-setup was then transferred into the HR-MAS NMR probe for analysis.A total of 36 spectra were acquired (center of tumor, n = 18; 5 cm from tumor margin, n = 18). The malignant clustering occurs due to increased Val (0.90ppm), Lac (1.34ppm), Ala(1.48ppm) levels of acetate (1.90ppm), glutamate (2.35ppm), taurine (3.23 ppm), choline containing compounds (3.20-3.22ppm), glycine (3.56ppm), lactate (4.12ppm) and α-H of Leu, Ileu, Val, Lys, Ala (3.76-3.79ppm . In addition unique metabolic profiles were observed for tumors of differing T-stage. The information gathered from clustering in PCA had highly suggested that malignancy induces metabolic perturbations at cellular levels.HR-MAS NMR profiling demonstrates cancer-specific metabolic signatures in CRC and reveals metabolic differences between benign and malignant tumors. In addition, this approach reveals that tumor metabolism undergoes modification during local tumor advancement, offering potential in future staging and therapeutic approaches.

67 STRATEGY FOR DEFINITIVE TREATMENT AND PRESERVING QUALITY OF LIFE IN UPPER CERVICAL ESOPHAGEAL CARCINOMA

In radical surgery for upper cervical esophageal carcinoma, questions such as whether the larynx should be preserved depending on the distance from the esophageal orifice to the tumor margin and risk of aspiration during swallowing arise. We report the clinical outcomes of our strategy for upper cervical esophageal carcinoma based on the goals of curability and larynx preservation. Methods At our institution, resectable upper cervical esophageal carcinoma in which the tumor margin on the oral side is within 3 cm of the esophageal orifice is treated with chemoradiotherapy followed by larynx-preserving esophagectomy. The reason for initially using chemoradiotherapy is to make the surgical margin on the oral side completely negative and as distal as possible for definitive treatment and to improve quality of life (QOL). From 2016 to 2019, there were 24 patients who were diagnosed with upper cervical esophageal carcinoma within 3 cm of the esophageal orifice and received chemoradiotherapy and larynx-preserving esophagectomy. Results All patients were eligible for chemoradiotherapy and larynx-preserving esophagectomy. Pathologically, all surgical margins on the oral side were negative and all operations were curative. In particular, 6 patients with a tumor margin within 1 cm of the esophageal orifice underwent successful curative, larynx-preserving esophagectomy with the following additional techniques: incision of the cricopharyngeus muscle, lifting of the trachea and larynx, and rotation of the larynx to the left. Regarding surgical complications, 4 patients had temporary recurrent nerve paralysis with aspiration pneumonia and 1 patient had minor anastomotic leakage. Conclusion The combination of chemoradiotherapy and esophagectomy with a larynx-preserving technique is a useful treatment strategy for upper cervical esophageal carcinoma in terms of both definitive treatment and QOL.

Diagnostic performance of imaging features in the HBP of gadoxetate disodium-enhanced MRI for microvascular invasion in hepatocellular carcinoma: a meta-analysis

Background Microvascular invasion (MVI) is a major risk factor for early recurrence in patients with hepatocellular carcinoma (HCC). Preoperative accurate evaluation of the presence of MVI could enormously benefit its treatment and prognosis. Purpose To evaluate and compare the diagnostic performance of two imaging features (non-smooth tumor margin and peritumor hypointensity) in the hepatobiliary phase (HBP) to preoperatively diagnose the presence of MVI in HCC. Material and Methods Original articles were collected from Medline/PubMed, Web of Science, EMBASE, and the Cochrane Library up to 17 January 2021 linked to gadoxetate disodium–enhanced magnetic resonance imaging (MRI) on 1.5 or 3.0 T. The pooled sensitivity, specificity, and summary area under the receiver operating characteristic curve (AUC) were calculated and meta-regression analyses were performed. Results A total of 14 original articles involving 2193 HCCs were included. The pooled sensitivity and specificity of non-smooth tumor margin and peritumor hypointensity were 73% and 61%, and 43% and 90%, respectively, for the diagnosis of MVI in HCC. The summary AUC of non-smooth tumor margin (0.74) was comparable to that of peritumor hypointensity (0.76) ( z = 0.693, P = 0.488). The meta-regression analysis identified four covariates as possible sources of heterogeneity: average size; time interval between index test and reference test; blindness to index test during reference test; and risk of bias score. Conclusion This meta-analysis showed moderate and comparable accuracy for predicting MVI in HCC using either non-smooth tumor margin or peritumor hypointensity in HBP. Four discovered covariates accounted for the heterogeneity.