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We compared the performance of computed tomography (CT) and magnetic resonance imaging (MRI) for preoperative clinical staging of mass‐forming intrahepatic cholangiocarcinoma (iCCA), using the eighth American Joint Committee on Cancer (AJCC) system. This retrospective, multicenter, cohort study consecutively identified patients who underwent partial hepatectomy for mass‐forming iCCA and had preoperative CT and MRI performed from January 2009 to December 2015. CT and MRI characteristics were used to determine clinical stage based on the eighth AJCC system. Performances of CT and MRI for clinical T and N staging were compared using generalized estimating equations. In 334 patients (median age, 63 years; 221 men), MRI sensitivities were significantly higher than CT sensitivities for detecting T1b or higher stages (91.0% vs. 80.5%, respectively, P 5 cm (i.e., T1b for single tumor) and extrahepatic organ invasion (i.e., T4). Sensitivities of CT and MRI were not different for N stage (65.0% vs. 64.0%, respectively, P = 0.808), but the specificity of CT was significantly higher than that of MRI (80.7% vs. 72.9%, respectively, P = 0.001) when using a composite reference standard. Conclusion: MRI showed superior sensitivity to CT for diagnosing T2 and T3 stages, particularly multiple tumors. CT and MRI had comparable sensitivity for N staging, but CT provided higher specificity than MRI.

Nucleic acids as the important tumor markers play a crucial role in the identification of cancer. Various kinds of probes such as gold nanoparticles and graphene oxide have been explored to detect different nucleic acid markers. However, the existing probes are mostly used to detect a single tumor marker and susceptible to harsh conditions in the complex and dynamic physiological environment, which may lead to false positive results and greatly limit the sensing performance of the probe. Herein, a powerful and reliable Au-Se probe was developed for high-fidelity imaging of two cancer markers simultaneously in living cells. Compared with the traditional nucleic acid probe based on the Au-S bond, this probe was more stable against biological thiols and could effectively distinguish normal cells and cancer cells to avoid false positive results, which is more suitable for imaging in a complex physiological environment. This strategy will provide more valuable insights into designing and exploring novel biosensors in the future.

The concurrence of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) in a single tumor is rarely encountered. We report a case of BCC and SCC in a single tumor in the anterior auricular area. A 70-year-old woman had been diagnosed with BCC by a punch biopsy performed at a dermatology clinic. We performed wide excision of the tumor with an ulcer in the anterior auricular area. Analysis of the biopsy specimen revealed the presence of both BCC and SCC in the tumor. This case illustrates that it is necessary to establish a precise diagnosis and formulate appropriate surgical and treatment plans considering the possibility that two carcinomas may coexist, although the possibility is low in patients with skin cancer.

BACKGROUND: While resection is a recommended treatment for patients with stage 1 hepatocellular carcinoma (HCC), it remains controversial for multifocal disease. We sought to identify patients with multifocal HCC with survival after resection similar to patients with clinical stage 1 HCC. METHODS: The National Cancer Database was queried to identify patients that underwent resection for HCC. RESULTS: In this study, 2990 patients with a single tumor, and 1087 patients with multifocal disease confined to one lobe underwent resection. In the multifocal cohort, patients with clinical stage 3 (HR 1.54, CI 1.31–1.81, p < 0.0001) or 4 (HR 2.27, CI 1.57–3.29, p < 0.0001) disease, and those with moderately-differentiated (HR 1.32, CI 1.06–1.64, p = 0.012) or poorly differentiated/undifferentiated tumors (HR 1.53, CI 1.20–1.95, p = 0.0006) were associated with worse overall survival (OS). There was no difference in OS between patients with well-differentiated clinical stage 2 multifocal HCC and those with all grades of clinical stage 1 HCC (median of 84.8 (CI 66.3–107.2) vs 76.2 months (CI 71.2–81.3), respectively, p = 0.356). CONCLUSIONS: Patients with well-differentiated, clinical stage 2 multifocal HCC confined to one lobe experience similar OS following hepatic resection to patients with clinical stage 1 disease. These findings may impact the management of select patients with multifocal HCC.

Background/purpose Few clinically useful biomarkers are known to predict prognosis in patients with hepatocellular carcinoma (HCC). The aim of this study was to investigate the correlation between PPAR activity and ALDH7A1 expression and their prognostic significance using RNA sequencing in patients undergoing liver resection for HCC. Methods We included patients undergoing liver resection for HCC at a tertiary referral center for hepato-pancreato-biliary surgery between May 2014 and January 2018. PPAR activity and ALDH7A1 expression were evaluated by RNA sequencing and correlated with overall survival, recurrence and histological features. Results We included 52 patients with a median follow-up of 20.9 months, predominantly males (88.5%) with a single tumor (84.6%) in a non-cirrhotic liver (73.1%). Three-year overall survival was 48.6% in patients with a specific PPAR target gene expression profile (cancer cluster 3) compared with 81.7% in controls (P = .04, Log-rank test). This remained significant (odds ratio 14.02, 95% confidence interval 1.92-102.22, P = .009) when adjusted for age, cirrhosis, microvascular invasion, number of tumors and free resection margins. ALDH7A1 expression was not correlated with PPAR or any outcomes. Conclusion PPAR activity in a subset of tumor samples was associated with reduced overall survival indicating that PPAR may be a valuable prognostic biomarker.

Background Patients with advanced neuroendocrine tumors (NETs) of the midgut are suitable candidates for 177Lu-DOTATOC therapy. Integrated SPECT/CT systems have the potential to help improve the accuracy of patient-specific tumor dosimetry. Dose estimations to target organs are generally performed using the Medical Internal Radiation Dose scheme. We present a novel Monte Carlo-based voxel-wise dosimetry approach to determine organ- and tumor-specific total tumor doses (TTD). Methods A cohort of 14 patients with histologically confirmed metastasized NETs of the midgut (11 men, 3 women, 62.3 ± 11.0 years of age) underwent a total of 39 cycles of 177Lu-DOTATOC therapy (mean 2.8 cycles, SD ± 1 cycle). After the first cycle of therapy, regions of interest were defined manually on the SPECT/CT images for the kidneys, the spleen, and all 198 tracer-positive tumor lesions in the field of view. Four SPECT images, taken at 4 h, 24 h, 48 h and 72 h after injection of the radiopharmaceutical, were used to determine their effective half-lives in the structures of interest. The absorbed doses were calculated by a three-dimensional dosimetry method based on Monte Carlo simulations. TTD was calculated as the sum of all products of single tumor doses with single tumor volumes divided by the sum of all tumor volumes. Results The average dose values per cycle were 3.41 ± 1.28 Gy (1.91–6.22 Gy) for the kidneys, 4.40 ± 2.90 Gy (1.14–11.22 Gy) for the spleen, and 9.70 ± 8.96 Gy (1.47–39.49 Gy) for all 177Lu-DOTATOC-positive tumor lesions. Low- and intermediate-grade tumors (G 1–2) absorbed a higher TTD compared to high-grade tumors (G 3) (signed-rank test, p = p = 0.01). Higher TTD resulted in a significant decrease of CgA after therapy. Conclusion These results suggest that Monte Carlo-based voxel-wise dosimetry is a very promising tool for predicting the absorbed TTD based on histological and clinical parameters.

Previous studies of the morphological features of head and neck squamous cell carcinomas revealed a significant association of the presence of discrete tumor cells and a low level of inflammatory infiltrate with lymphogenous metastasis. The aim of the study was to evaluate the quantity of tumor cells undergoing epithelial-mesenchymal transition (EMt) in tumor cell structures of different degrees of differentiation and to assess the prognostic model of lymphogenous metastasis based on the studied parameters. M aterial and methods . the main clinical tumor characteristics and morphological patterns of the tumor were assessed in 92 patients. the expressions of snail and Vimentin proteins were studied in 16 patients using confocal microscopy. Results. t he expression of the EMt marker in cell structures of different degrees of differentiation was evaluated; the maximum number of snail- and Vimentin-positive cells (20 % each) was observed in discrete tumor cells. No difference in the proportion of cells undergoing epithelial-mesenchymal transition between patients with and without lymphogenous metastasis was found. thus, the prognostic model of lymphogenous metastasis included: the presence of single tumor cells and low level of inflammation. the sensitivity of the model was 54.5 %, and specificity was 89 %.

Introduction. Metastases of breast cancer are detected in 5 to 48% cases, depending on the biological tumor subtype, which is the second most common after lung cancer in men. Cytological liquor analysis is one of the “gold standards” for the metastatic brain lesion identification, and, among other modern approaches, it can increase the CNS metastasis detection. Breast cancer cell identification in cerebrospinal fluid is a poor prognostic factor. A cytological examination has a predictive significance for these patients: the absence of tumor cells in the cerebrospinal fluid can be considered the sign of the intrathecal therapy effectiveness. The accuracy of the cytological diagnosis directly depends on the detailed patient’s history. Immunocytochemical assays increase the sensitivity of the cytological diagnostics. The aim of the study was to evaluate the ca-pabilities of comprehensive cytological and immunocytochemical studies in the secondary cerebral lesions diagnosis in breast cancer patients. Materials and methods. We conducted 169 cytological studies in 55 breast cancer patients with brain metas-tases. Liquor samples were obtained using lumbar punctures. 36 patients underwent 44 immunocytochemical studies and 117 immunocytochemical reactions to clarify the cytological diagnosis. Results. The sensitivity of the cytological method was 69.8%. Immunocytochemistry increased the sensitiv-ity to 72.3%. In 29 patients, the tumor histogenesis was determined using an immunocytochemical assay. Conclusion. The liquor cytological analysis is frequently the only primary morphologic diagnostic method to detect breast cancer metastasis within the central nervous system. Immunocytochemical assay significantly expands the possibilities of cytological study, allowing health care specialists to detect single tumor cells in samples and determine the metastatic neoplasm histogenesis in most cases, which also increases sensitivity. Keywords: breast cancer, cytological and immunocytochemical study of cerebrospinal fluid

Hepatic pseudolymphoma is a very rare benign reactive lymphoid hyperplasia associated with autoimmunity and chronic inflammatory liver diseases such as primary biliary cirrhosis and may mimic hepatocellular carcinoma. This diagnosis should be suspected in female with a suspicious single tumor. Close monitoring is needed in view of its premalignant nature.

Objective: at the primary analysis of prostate cancer treatment referring to the patients who have experienced high dose rate brachytherapy after a confirmed locally recurrent tumor having been treated with diverse treatment modes.Materials and methods. The research includes 28 patients aged 53 to 78 years old (average age is 66 years old) with histologically verified prostate cancer recurrence. Within the period 2015–2017 all the patients got a salvage high dose rate brachytherapy in the Russian Scientific Center of Roentgenradiology. Brachytherapy was carried out as 2 fractions with the single tumor dose of 12.5 Gy. There was a two-week gap between fractions with the total tumor dose of 25 Gy. The follow-up period is 9 to 36 months.Results and conclusion. Overall biochemical free survival rate is 82.1 %. There are 5 people having a growing prostatic specific antigen (PSA) while the case follow-up. There is 1 case of a confirmed local tumor recurrence. Significant factors of the disease progression after salvage brachytherapy are: risk group, pretreatment PSA high, time line from the background therapy to biochemical recurrence uprise and PSA level if there’s prostate cancer recurrence after the background therapy.

Surgical treatment of a giant cell tumor (GCT) remains a complex and urgent problem. Its tactics depend on the size and location of GCT. Age of the patient, the presence of pathological fractures, invasion of blood vessels and nerves. Objective: to study the results of modular Endoprosthetics of the proximal tibial (PT) in case of a GCT injury. Methods: the study group included 16 patients (9 women, 7 men, age from 18 to 56 years) with GCT of PT (stage III according to the classification of Enneking). Patients were examined according to generally accepted methods, X-rays, CT scans (if angio CT was necessary), and Biopsy were performed. Surgical treatment: resection of PT with GCT «en block», modular endoprosthetics recostruction with the MUTARS Implant cast system (6 patients), CИMEКС (9) and GMRS Stryker (1), soft tissue reinsertion to the endoprosthesis body, knee-joint extension plastic. The capsule of the suspension and the patella bundles were fixed on an Attachment tube (СИМЕКС and MUTARS systems) or using a nylon ribbon (GMRS Stryker). For the evaluation used the scale MSTS and TESS. Results: patients returned to normal life on average 2–2.5 months. The functional results on the MSTS scale were (72 ± 12) %, on the TESS scale — (74 ± 16) % and were classified as good. During the observation period of 6 months. up to 14 years not a single tumor recurrence was detected. Results: 2 (12.5 %) — periprosthetic infection, 1 (6.2 %) — traumatic damage to the extensor apparatus. Conclusions: resection of «en blok» in the case of Enneking stage III GCT made it possible to avoid oncological complications during the observation period up to 14 years. The use of modular endoprostheses, the reinstallation of soft tissues on the body of the endoprosthesis and the plastic of the extension apparatus of the knee joint, the early activation of the patient contributed to the achievement of a good functional result.

Whereas in vivo fluorescence imaging of cells immobilized within tissues provides a valuable tool to a broad range of biological studies, it still lacks the sensitivity required to visualize isolated cells circulating fast in the bloodstream due, in particular, to the autofluorescence from endogenous fluorophores. Time-gated imaging of near-infrared emitting ZnCuInSe/ZnS quantum dots (QDs) with fluorescence lifetimes in the range of 150-300 ns enables the efficient rejection of fast autofluorescence photons and the selection of QD fluorescence photons, thus significantly increasing sensitivity. We labeled model erythrocytes as well as lymphoma cells using these QDs coated with a stable zwitterionic polymer surface chemistry. After reinjection in the bloodstream, we were able to image and count individual QD-labeled cells circulating at mm·s-1 velocities in blood vessels.

The fundamental principle of precision oncology is centralized on the identification of therapeutically exploitable targets that provides individual patients with cancer an opportunity to make informed decisions on a personalized level. To facilitate and adopt such concepts within clinical practice, we have initiated a nationwide, multi-institutional precision oncology screening program to examine and enroll patients into the most appropriate clinical trial based on their tumor's unique molecular properties. To determine the prevalence of essential major driver mutations and to explore their dynamic associations at both molecular and pathway levels, we present a comprehensive overview on the genomic properties of East Asian patients with cancer. We further delineate the extent of genomic diversity as well as clinical actionability in patients from Western and Eastern cultures at the pan-cancer and single-tumor entity levels. To support fellow oncology communities in future investigations involving large-scale analysis, all data have been made accessible to the public (https://kmportal.or.kr). Significance: We present a comprehensive overview of molecular properties of East Asian pan-cancer patients and demonstrate significant diversity in terms of genomic characteristics as well as clinical utility compared with patients with European ancestry. The results of this study will lay the groundwork for designing personalized treatments in the clinical setting. See related commentary by Moyers and Subbiah, p. 886. This article is highlighted in the In This Issue feature, p. 873

Retinoblastoma (Rb) is the most common pediatric ocular malignancy and accounts for 2% of all childhood cancers. Rb is initiated by a mutation of the RB1 tumor suppressor gene and occurs in 2 forms: 1) unilateral and unifocal, characterized by a single tumor in 1 eye, and 2) bilateral or unilateral, multifocal Rb with multiple tumor foci in 1 or both eyes. Rb is a disease of young children and if left untreated can result in visual morbidity as well as systemic mortality. Fortunately, because of the greater availability of genetic testing and earlier diagnosis, novel targeted therapies, and multimodal treatment approaches, disease-free survival rates and visual prognoses have improved dramatically. Current efforts to expand the accessibility of the newest Rb treatments aim to improve Rb outcomes worldwide. In this article, we will review the clinical presentation, diagnosis, and management of Rb, with a focus on the newest treatment approaches.

Modern surgical technologies allow gynecologists to treat most submucosal myomas hysteroscopically by some form of resection. What appears on imaging or direct visualization to be a submucosal myoma can be a single tumor, or may represent multiple smaller myomas appearing as one, compacted together in a typical pseudo capsule. During myoma resection, the effect of the media used to induce distension can vary, depending on the morphology of the myomas. After starting resection, the pressure of the distending media can push truly solitary myomas to somewhat flatten against the uterine wall. However, in the second type of myoma, the fluid can displace the myomas into the uterine cavity, an appearance similar to the blooming of a flower. The tip of the hysteroscope may enter the dissected spaces between the myomas, which impairs the panoramic view. This phenomenon may cause inadequate treatment of the myomas encountered during hysteroscopic myomectomy. In this study, the “Blooming phenomenon” is introduced, and the problems created by this phenomenon and solutions for its management are considered.

Laparoscopic liver resection (LLR) has been reported as a safe, minimally invasive, and effective surgery for the management of liver tumor. However, the efficacy and safety of laparoscopic repeat liver resection (LRLR) for recurrent liver tumor are unclear. Here, we analyzed the surgical results of LRLR. From June 2010 to May 2019, we performed 575 LLR surgeries in our department, and 454 of them underwent pure LLR for the single tumor. We classified the patients who received pure LLR for the single tumor into three groups: LRLR (n = 80), laparoscopic re-operation after previous abdominal surgery (LReOp; n = 136), and laparoscopic primary liver resection (LPLR; n = 238). We compared patient characteristics and surgical results between patients undergoing LRLR, LReOp and LPLR. We found no significant differences between LRLR and LPLR in the conversion rate to laparotomy (p = 0.8033), intraoperative bleeding (63.0 vs. 152.4 ml; p = 0.0911), or postoperative bile leakage rate (2.50 vs. 3.78%; p = 0.7367). We also found no significant difference in the surgical results between LReOp and LPLR. However, the number of patients undergoing the Pringle maneuver was lower in the LRLR group than the LPLR group (61.3 vs. 81.5%; p = 0.0004). This finding was more pronounced after open liver resection than laparoscopic liver resection (38.9 vs. 67.7%; p = 0.0270). The operative time was significantly longer in patients with proximity to previous cut surface than patients with no proximity to previous cut surface (307.4 vs. 235.7 min; p = 0.0201). LRLR can safely be performed with useful surgical results compared to LPLR.

Atypical teratoid rhabdoid tumor (ATRT) is an aggressive embryonal brain tumor among infants and young children. Two challenges exist for preclinical testing in ATRT. First, genetically quiet, ATRT is a difficult tumor to target molecularly. Tumor cells need to divide to propagate tumor growth—intercepting the common crossroads in cell cycle progression is a feasible strategy. KIF11 is needed for bipolar spindle formation in metaphase. We identified KIF11 as a universal target of all ATRT-molecular-subtypes. Ispinesib, a KIF11-inhibitor, effectively inhibited tumor proliferation in all seven cell lines. A second challenge—a major challenge in preclinical drug testing in-vivo among aggressive tumor models, is the narrow therapeutic window to administer drugs within the limited murine lifespan. Our most aggressive ATRT tumor model was lethal in all mice within ~ 1 month of tumor implantation. Such short-surviving mouse models are difficult to employ for preclinical drug testing due to the narrow time window to administer drugs. To overcome this time restriction, we developed a clinical staging system which allowed physically-fit mice to continue treatment, in contrast to the conventional method of fixed drug-dose-duration regimen in preclinical testing which will not be feasible in such short-surviving mouse models. We validated this approach in a second embryonal brain tumor, medulloblastoma. This is a clinically relevant, cost-efficient approach in preclinical testing for cancer and non-cancer disease phenotypes. Widely used preclinical mouse models are not the most accurate and lack the aggressive tumor spectrum found within a single tumor type. Mice bearing the most aggressive tumor spectrum progress rapidly in the limited murine life-span, resulting in a narrow therapeutic window to administer drugs, and are thus difficult to employ in preclinical testing. Our approach overcomes this challenge. We discovered ispinesib is efficacious against two embryonal brain tumor types.

The aim of the present study was to evaluate the effect of counting increasing number of invasive cancer cells in the result of the HER2 in situ hybridization (ISH) test in breast cancer as well as to compare two different approaches of measuring genomic heterogeneity (single cell and population based). A cohort of 100 consecutive breast cancer cases (primary and metastatic) were evaluated for HER2 gene amplification with bright-field ISH. The evaluation of the samples included scoring 20 nuclei, in five different areas, measuring the margins of error for each case. Genomic heterogeneity (GH) was defined by the 2018 ASCO/CAP guideline as a discrete population of tumor cells with HER2 amplification. We also evaluated GH as single tumor cells with HER2 amplification. The stabilization of the coefficient of variation of HER2/CEP17 ratio requires about 60 invasive cancer cells. The average margin of error of HER2/CEP17 ratio and of HER2 copy number was 0.40 and 0.53, respectively, when counting 20 cells, decreasing to 0.20 and 0.26 when counting 100 cells. Population GH was observed in 1% of the cases, while single cell GH was observed in 27% of the cases, reaching its maximum value in cases near the thresholds of positivity. Therefore, margins of error in HER2 ISH test are high, and the minimal cell number recommended in current guidelines should be raised to at least 60 cells. Population GH is a rare event and single cell GH is maximal in cases near the thresholds.

Simple Summary Despite great advances in cancer therapy, tumor heterogeneity continues to be a great barrier for the successful treatment of cancer. It has long been established that tumor heterogeneity is prevelant in most cancer patients and is a major driver of acquired resistance to all forms of cancer therapy. In the case of immunotherapy, the response of the immune system against specific tumor antigens can drive selective pressure towards antigen-negative cells, which is a common cause of relapse in the clinic. In this review we summarize the mechanisms in which tumor heterogeity can arise. Furthermore, we discuss recent advances in the field of oncology that can be used to better identify, study, and overcome tumor heterogeneity. Abstract Throughout the history of oncology research, tumor heterogeneity has been a major hurdle for the successful treatment of cancer. As a result of aberrant changes in the tumor microenvironment such as high mutational burden, hypoxic conditions and abnormal vasculature, several malignant subpopulations often exist within a single tumor mass. Therapeutic intervention can also increase selective pressure towards subpopulations with acquired resistance. This phenomenon is often the cause of relapse in previously responsive patients, drastically changing the expected outcome of therapy. In the case of cancer immunotherapy, tumor heterogeneity is a substantial barrier as acquired resistance often takes the form of antigen escape and immunosuppression. In an effort to combat intrinsic resistance mechanisms, therapies are often combined as a multi-pronged approach to target multiple pathways simultaneously. These multi-therapy regimens have long been a mainstay of clinical oncology with chemotherapy cocktails but are more recently being investigated in the emerging landscape of immunotherapy. Furthermore, as high throughput technology becomes more affordable and accessible, researchers continue to deepen their understanding of the factors that influence tumor heterogeneity and shape the TME over the course of treatment regimens. In this review, we will investigate the factors that give rise to tumor heterogeneity and the impact it has on the field of immunotherapy. We will discuss how tumor heterogeneity causes resistance to various treatments and review the strategies currently being employed to overcome this challenging clinical hurdle. Finally, we will outline areas of research that should be prioritized to gain a better understanding of tumor heterogeneity and develop appropriate solutions.

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. Despite aggressive multimodal treatment, relapse is inevitable with patients succumbing to disease 15 months after diagnosis. Poor prognosis may be attributed to significant intratumoral heterogeneity at the genomic, cellular, and functional levels of a single tumor. However, this heterogeneity highlights the need to understand mechanisms of therapeutic resistance to give insight into the underpinnings of treatment failure. Thus, we review some of the various tumor-intrinsic molecular mechanisms, as well as tumor-extrinsic factors that support GBM progression and therapeutic resistance.

Next-generation sequencing assays are capable of identifying cancer patients eligible for targeted therapies and can also detect germline variants associated with increased cancer susceptibility. However, these capabilities have yet to be routinely harmonized in a single assay because of challenges with accurately identifying germline variants from tumor-only data. We have developed the Oncology and Hereditary Cancer Program targeted capture panel, which uses tumor tissue to simultaneously screen for both clinically actionable solid tumor variants and germline variants across 45 genes. Validation using 14 tumor specimens, composed of patient samples and cell lines analyzed in triplicate, demonstrated high coverage with sensitive and specific identification of single-nucleotide variants and small insertions and deletions. Average coverage across all targets remained >2000× in 198 additional patient tumor samples. Analysis of 55 formalin-fixed, paraffin-embedded tumor samples for the detection of known germline variants within a subset of cancer-predisposition genes, including one multiexon deletion, yielded a 100% detection rate, demonstrating that germline variants can be reliably detected in tumor samples using a single panel. Combining targetable somatic and actionable germline variants into a single tumor tissue assay represents a streamlined approach that can inform treatment for patients with advanced cancers as well as identify those with potential germline variants who are eligible for confirmatory testing, but would not otherwise have been identified.

Background The aim of the present study was to evaluate the prognosis among patients with a single large hepatocellular carcinoma (HCC) >5 cm compared with other patients in Barcelona Clinic Liver Cancer (BCLC) stage A or stage B. Material/Methods Data on patients with BCLC stage A/B HCC were collected between 2008 and 2012. BCLC stage A was subclassified as A1 (single tumor, 2–5 cm, or 2–3 nodules ≤3 cm), or A2 (single tumor >5 cm). Overall survival (OS) was evaluated and compared. Results Among 1005 patients with HCC, 455 were stage A1, 188 were stage A2, and 362 were stage B. The OS of stage A2 patients was significantly worse than that of stage A1 patients (median survival, 30.6 vs. 43.2 months, p5 cm had a comparable survival with BCLC stage B. HCC >5 cm should therefore be classified as an intermediate stage.

Background Multiplexed immunofluorescence (mIF) allows the visualization of multiple biomarkers in a single tumor tissue section, while at the same time preserving the spatial biology of the tumor microenvironment (TMI). CO-Detection by indEXing (CODEX®) and Phenoptics™ platforms are complementary mIF technologies that span the full spectrum of cancer research, from discovery to translational and clinical research. CODEX® is ultra-high plex and allows imaging of up to 40 antigens on a single tissue section with single-cell resolution. Phenoptics™ is an established mIF platform that enables high-throughput whole slide multispectral image acquisition and tissue interrogation with up to 8 markers plus DAPI. Here we present a study that compares shared sets of immune and tumor markers between the CODEX® and Phenoptics™ platforms. This cross-platform comparison provides a conceptual framework for researchers to translate biomarker signatures from discovery to high-throughput translational studies. Materials and Methods Serial sections of human formalin-fixed paraffin embedded non-small cell lung cancer (NSCLC) and tonsils were analyzed. An initial screen with a 28-plex CODEX® antibody panel revealed multiple biomarkers of interest, including CK, CD8, Ki67, PD-L1 and PD-1; all of these biomarkers showed abundant expression in the TMI. Building on this result, we next developed a 6-plex Opal™ Phenotpics™ panel. This panel was screened and analyzed via high-throughput whole slide scanning of sample tissues. Image processing and data analysis were conducted similarly for both datasets so that repeatability and consistency of measurements could be established. Results Both CODEX® and Phenoptics™ detected the same cell phenotypes and displayed similar frequencies of cells expressing CK, CD8, Ki67, PD-L1 and PD-1 in serial sections of tonsil and NSCLC tissues. These observations were consistent and cross-validated in data from CODEX® and Phenoptics™ platforms. Crucially, this means that the two approaches can be made analytically equivalent, and hence, that they can be used in conjunction with each other as research progresses along the continuum from discovery to translational and clinical research. Conclusions Our cross-platform comparison provides a conceptual framework for biomarkers discovered on the CODEX® platform to be translated to the Phenoptics™ platform for high-throughput translational studies. The resulting comprehensive phenotyping and quantification data retain spatial context and provide unprecedented insight into tumor biology. Disclosure Information O. Braubach: A. Employment (full or part-time); Significant; Akoya Biosciences. M. Gallina: A. Employment (full or part-time); Significant; Akoya Biosciences. B. Remeniuk: A. Employment (full or part-time); Significant; Akoya Biosciences. C. Wang: A. Employment (full or part-time); Significant; Akoya Biosciences. N. Nikulina: A. Employment (full or part-time); Significant; Akoya Biosciences. R. Bashier: A. Employment (full or part-time); Significant; Akoya Biosciences. J. Kennedy-Darling: A. Employment (full or part-time); Significant; Akoya Biosciences. C. Hoyt: A. Employment (full or part-time); Significant; Akoya Biosciences.

Mammosphere assays are widely used in vitro to identify prospective cancer-initiating stem cells that can propagate clonally to form spheres in free-floating conditions. However, the traditional mammosphere assay inevitably introduces cell aggregation that interferes with the measurement of true mammosphere forming efficiency. We developed a method to reduce tumor cell aggregation and increase the probability that the observed mammospheres formed are clonal in origin. Tethering individual tumor cells to lipid anchors prevents cell drift while maintaining free-floating characteristics. This enables real-time monitoring of single tumor cells as they divide to form mammospheres. Monitoring tethered breast cancer cells provided detailed size information that correlates directly to previously published single cell tracking data. We observed that 71% of the Day 7 spheres in lipid-coated wells were between 50 and 150 μm compared to only 37% in traditional low attachment plates. When an equal mixture of MCF7-GFP and MCF7-mCherry cells were seeded, 65% of the mammospheres in lipid-coated wells demonstrated single color expression whereas only 32% were single-colored in low attachment wells. These results indicate that using lipid tethering for mammosphere growth assays can reduce the confounding factor of cell aggregation and increase the formation of clonal mammospheres.

High-resolution imaging of sentinel lymph nodes (SLN) from melanoma patients is a crucial approach to specify staging and determine individuals requiring adjuvant treatment. Current histologic SLN analysis has the substantial drawback that only a small portion of the node is sampled while most of the tissue is discarded which might explain the high false-negative rate of SLN diagnosis. Therefore, we developed an algorithm-enhanced light sheet fluorescence microscopy (LSFM) approach to three-dimensionally reconstruct the entire SLN with the power to identify single tumor cells. We comprehensively quantified total tumor volume while simultaneously visualizing cellular and anatomical hallmarks of the associated SLN architecture. In a first-in-human prospective study (21 SLN from 11 melanoma patients), LSFM not only identified all metastases seen histologically, but additionally detected metastases not recognized by routine histology. Thus, our 3-D digital pathology approach can increase sensitivity and accuracy of SLN-metastasis detection and potentially alleviate the need for conventional histopathological assessment in the future. Contact: Professor Dr. Joachim Klode University Hospital Essen Department of Dermatology Hufelandstrase 55, 45147 Essen, Germany Phone.: +49 201 723-1812 Fax: +49 201 723-5424 E-Mail: joachim.klode@uk-essen.de Professor Dr. Matthias Gunzer University Hospital Essen Institute for Experimental Immunology and Imaging Hufelandstrase 55, 45147 Essen, Germany Phone: +49 201 183 6640 Fax: +49 201 183 6642 E-Mail: matthias.gunzer@uni-due.de

A novel palpation-based tumor detection method for robot-assisted minimally invasive surgery (RMIS) is proposed in this paper. A tactile stiffness sensor based on piezoelectric vibration is designed to detect tissue stiffness just by gentle contacting, without the risk of injuring the organ. A novel multi-tumor detection method is proposed to solve the problem that existing tumor detection methods can only detect a single tumor. In addition, the moving distance of the sensor during palpation is introduced into the sampling strategy function as a new factor, so that the total moving distance of sensor can be considered and optimized during the tumor palpation process. Simulation studies are carried out to compare the new method with existing methods in tumor detection. It shows that the proposed method can identify and locate multiple tumors successfully with the highest performance (F1 score > 0.99), and the total moving distance during palpation is reduced by 43% without any compromise in the detection accuracy.

Melanoma is the deadliest form of skin cancer and one of few cancers with a growing incidence. A thorough understanding of its pathogenesis is fundamental to developing new strategies to combat mortality and morbidity. Zebrafish—due in large part to their tractable genetics, conserved pathways, and optical properties—have emerged as an excellent system to model melanoma. Zebrafish have been used to study melanoma from a single tumor initiating cell, through metastasis, remission, and finally into relapse. In this review, we examine seminal zebrafish studies that have advanced our understanding of melanoma.

To maximize survival benefit, the LT community should consider reducing (or eliminating) priority for the 10% to 20% of patients with HCC with very long wait‐list life expectancy (e.g., Child‐Pugh A, low MELD and AFP, and single tumor up to 3 cm with complete response to LRT). On the other end of the tumor burden spectrum, some determination of tumor biology should be obtained in patients presenting beyond Milan criteria (in addition to AFP). Reasonable approaches include LRT for tumor down‐staging, measuring novel biomarkers such as AFP‐L3 and DCP, and PET scan. Results from the various proposed pre‐LT models (Table ​(Table3)3) that include such criteria have suggested that acceptable post‐LT outcome can be achieved in selected patients with HCC beyond Milan criteria. Although it is impossible to compare all of these selection models, the optimal LT criteria should be center specific, taking into account the availability of donor organs and what post‐LT outcome is considered acceptable. Centers performing primarily LDLT may be willing to accept lower 5‐year post‐LT survival rates by using less restrictive criteria than centers with significant organ shortages, where post‐LT outcome for patients with or without HCC should be similar.

Tumor budding (TB) is a histopathologically evident feature that represents a scattered pattern of invasion consisting of isolated single tumor epithelial cells or tumor cells in small clusters (up to 5 cells) seen primarily at the invasive front dispersed within the stroma for variable distance. Presence of TB has been linked with lymph node metastasis, recurrence, distant metastasis and reduced survival in numerous cancers including oral squamous cell carcinoma (OSCC). Tumor buds are also considered as histopathological markers of epithelial-mesenchymal transition which is a molecular process implicated as a hallmark for invasion and metastasis. This review gives an overview of the current evidence regarding TB assessment in OSCC and its future prospects.

Molecular analysis of rare single cells like circulating tumor cells (CTCs) from whole blood patient samples bears multiple challenges. One of those challenges is the efficient and ideally loss‐free isolation of CTCs over contaminating white and red blood cells. While there is a multitude of commercial and non‐commercial systems available for the enrichment of CTCs their cell output does not deliver the purity most molecular analysis methods require. Here we describe the ALS CellCelector™ which can solve this challenge allowing the retrieval of 100% pure single CTCs from blood processed by different upstream enrichment techniques. It is a multifunctional, extremely flexible system for automated screening of cell culture plates, Petri dishes, and microscope slides. Fixed or live single cells or multicellular clusters detected during screening can be picked out of those plates automatically. The complete scan and picking process is fully documented hence allowing highest standardization and reproducibility of all processes. Use of CellCelector allowed the isolation of pure single tumor cells or clusters from liquid biopsies of breast, prostate, ovarian, colorectal, lung, and brain cancers for their subsequent molecular analysis. © 2018 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.

Tujuan : Membandingkan penanda tumor osteopontin (OPN), cancer antigen 125 (CA125), kombinasi sebagai prediktor keganasan pada penderita tumor ovarium. Metode : Penelitian cross sectional ini dilakukan pada pasien dengan keganasan pada kista ovarium jenis epitel. Analisis data dilakukan secara univariat dan bivariat. Hasil : 47 pasien dengan hasil hitopatologi jinak dan 43 dengan hasil histopatologi ganas masuk dalam penelitian. Hasil nilai median CA125 kelompok ganas dibanding kelompok jinak (142,2 vs 61,030, p < 0,05), cut off point CA125 99,9 U/mL, sensitivitas 76,7% dan spesifisitas 61,7%. Diskusi: Kombinasi CA125 dan OPN memiliki sensitivitas lebih rendah dibandingkan CA125. Kombinasi CA125 dan OPN akan meningkatkan spesifitas, nilai duga positif dan akurasi yang lebih baik. Tumor marker OPN tidak tepat digunakan untuk proses deteksi dini, tetapi lebih tepat untuk penegakan diagnosis lebih baik dibandingkan dengan gold standard CA125. Kesimpulan : Kombinasi OPN dan CA125 memiliki nilai tingkat akurasi paling tinggi apabila dibandingkan pemeriksaan tunggal CA125, OPN. Single Check of Serum Ostepontin and CA 125 Levels as A Predictor of Malignancy in Epitheliaal Ovarium Tumor is Inferior to Combined Examination Abstract Objective : To compare the sensitivity, specificity, expected value positive, expected value negative and accuracy among osteopontin (OPN), cancer antigen 125 (CA125), and combination as predictor of malignancy in ovarian tumor patients. Method : A cross sectional study was done to compare parameters OPN and CA125 in determining malignancy of ovarian cysts. Data analysis was performed by univariate and bivariate analysis. Results: A total of 47 subjects were included with benign histopathological result and 43 subjects with malignant histopathological result. The median value of CA125 in malignant group was compared to that of benign group (142.2 vs. 61.030, p value

Ovarian cancer encompasses a collection of neoplasms with distinct clinicopathological and molecular features and prognosis. Despite there being a variety of ovarian cancer subtypes, these are treated as a single disease. Tremendous efforts have been made to characterize these subtypes and identify tumoral pathways and potential biomarkers for therapeutic strategies. As in other cancer types, tumor heterogeneity appears to be very high across subtypes and within a single tumor, representing a major cause of treatment failure. We describe the morphological and molecular heterogeneity among ovarian cancers and discuss recent advances in our understanding of intratumor heterogeneity.

Objective : to analyze the association of 5 types of cellular structures of squamous cell carcinoma with major clinical and morphological tumor characteristics. Material And Methods . The main clinical and morphological characteristics of the primary tumor were assessed in 74 patients. Results . Single tumor cells and structures formed by polymorphic cells were observed in primary tumor more often in the patients with metastatic lymph nodes than in patients with intact lymph nodes. Furthermore, inflammatory reaction in the patients with metastatic lymph nodes was significantly lower than in the patients with intact lymph nodes. Conclusion . Morphological heterogeneity of the tumor allows us to suggest the clinical course of the head and neck squamous cell carcinoma.

Inference of intra-tumor heterogeneity can provide valuable insight into cancer evolution. Somatic mutations detected by sequencing can help estimate the purity of a tumor sample and reconstruct its subclonal composition. Although several methods have been developed to infer intra-tumor heterogeneity, the majority of these tools rely on variant allele frequencies as estimated via ultra-deep sequencing from multiple samples of the same tumor. In practice, obtaining sequencing data from a large number of samples per patient is only feasible in a few cancer types such as liquid tumors, or in rare cases involving solid tumors selected for research. We introduce CTPsingle, which aims at inferring the subclonal composition by using low-coverage sequencing data from a single tumor sample. We show that CTPsingle is able to infer the purity and the clonality of single-sample tumors with high accuracy, even restricted to a coverage depth of ∼30 × .

The attempts to identify, isolate and characterize cancer stem cell populations are mostly dependent on cell-surface markers. In breast cancer, several putative breast cancer stem cell (BCSC) markers have already been reported, but the agreement on their phenotypic characterization is still absent. In fact, it became unfeasible to obtain a universal combination of markers that could specifically identify BCSCs in all cases of breast cancer. Breast cancer heterogeneity as reflected by various histological subtypes, with variable clinical presentations and diverse molecular signatures also contributes to major drawbacks. Indeed, intra-tumor heterogeneity leads to a single tumor to contain, at any given time, tumor cell populations displaying different molecular profiles and biological properties. As a consequence, several BCSC phenotypes were described, with some being associated with aggressive forms of breast cancer. Although the validation of the CSC model remains an ongoing task, it is important to define which BCSC phenotypes have high tumorigenic potential and ability to resist therapeutic agents. For this reason, a concise review is presented here regarding the implications of the most studied BCSC markers and phenotypes in breast cancer progression and treatment.

Background Total tumor volume (TTV) can provide a simplified parameter in describing the tumor burden by incorporating the size and number of tumor nodules into one continuous variable. The aim of the study was to evaluate the prognostic value of TTV in resection of hepatocellular carcinoma (HCC). Methods Patients who underwent liver resection for HCC between 2012 and 2017 were retrospectively analyzed. Patients were divided into a group with TTV ≤65.5 cm³ (which nearly equal to a single tumor with a diameter of 5 cm), and another group with TTV > 65.5 cm³. Results Two hundred and four patients were included in this study (108 patients had TTV ≤ 65.5cm3, and 96 patients had TTV > 65.5 cm³). Ninety patients (44.1%) were within Milan and 114 patients (55.9%) were beyond Milan criteria. Eighteen patients (15.8%) of beyond Milan criteria had TTV ≤ 65.5 cm³, with a median survival of 32 months which is comparable to a median survival of patients with TTV< 65.5 cm³ (38 months, P = 0.38). TTV-based Cancer of Liver Italian Program (CLIP) score gained the highest value of likelihood ratio 114.7 and the highest Concordance-index 0.73 among other prognostic scoring and staging systems. In multivariate analysis, independent risk factors for diminished survival were serum AFP level >400 ng/ml, TTV >65.5 cm³, microvascular invasion, postoperative decompensation (all P values, Highlights • Total tumor volume (TTV) can provide a simplified parameter in describing the tumor burden. • This can be done by incorporating the size and number of tumor nodules into one continuous variable. • TTV, has been shown as a useful prognostic parameter in the prediction of tumor recurrence and survival in liver transplantation. • However, there is still a scarce clinical series that describe the prognostic value of TTV in liver resection. • TTV- CLIP score may provide good prognostic value for resection of HCC than other staging systems.

Background The clinical manifestation of hepatocellular carcinoma (HCC) with hepatitis B virus (HBV) varies significantly between patients treated with or without nucleos(t) ide analog (NUC) therapy. To have a better understanding of HCC with HBV, we compared the clinical features of patients with HCC receiving or not receiving NUC therapy. Methods We retrospectively reviewed the medical records of 76 patients with HBV-caused HCC who received treatment at the Hunan Provincial Peoples’ Hospital starting from January 1, 2008 to December 31, 2017. They were categorized into two groups, namely, NUC group and non-NUC group, based on whether they had received NUC therapy or not. Results The percentage of liver pain (36.36% vs. 79.07%; p p p p p = 0.370) and ALB (p = 0.475). The same trend was observed for the proportion of HBeAg negative (p = 0.719) and AFP ≤ 14.65 ng/mL (p = 0.199) in both groups. Single tumor nodule was more common in the NUC group compared to the non-NUC group (66.67% vs. 6.98%; p p p Conclusions Nucleos(t) ide analog therapy exerts a significant impact on the clinical and radiological characteristics of hepatocellular carcinoma with HBV. Patients receiving nucleos(t) ide analog therapy were found to have milder symptoms and fewer radiographic findings.

Colorectal cancer (CRC) related death has often been attributed to the presence of metastatic disseminated disease. A concise understanding of the molecular mechanism(s) that drive metastatic progression is therefore needed but has thus far been hampered by the limited number of CRC mouse models that progress toward this disease stage. In addition, preclinical evaluation of therapeutic modalities aimed at managing metastatic disease also rests on the availability of relevant in vivo models that faithfully recapitulate the key molecular features of metastatic human CRC. To overcome these limitations, we have recently developed methodologies that enable the study of CRC progression at relevant orthotopic sites. Here, we provide a detailed methodology that describes the injection of CRC derived cell lines and organoids directly into the colorectal mucosa. This results in the growth of a single tumor mass within the colon, that can spontaneously metastasize to the liver. Furthermore, we also present a surgical procedure to directly inject cells into the portal venous circulation to induce CRC tumor growth in the liver without the requirement of a primary tumor.

Plasmacytomas can have different clinical presentations. They can be observed as a single tumor mass without bone marrow involvement (solitary plasmacytoma) or in the context over multiple myeloma. In rare instances plasmacytomas are triggered by invasive surgical procedures. These different types of plasmacytomas can be found in the same patient which suggests a special biology of the malignant plasma cell that facilitates the spread outside the bone marrow. Here, we report the unique case of a 37-year-old man with solitary bone plasmacytoma with soft-tissue involvement who progressed to multiple myeloma with a huge mass at the scar of inguinal hernia surgery performed 10 years before. Throughout the course of the disease, he developed extensive multiple paraskeletal and extramedullary plasmacytomas at different locations.

To describe the magnetic resonance imaging (MRI) features of hepatocellular carcinoma (HCC) in patients with non-alcoholic steatohepatitis (NASH).MRI examinations of 21 patients with HCC and NASH were analyzed by two observers. There were 18 men and 3 women with a mean age of 67.9 ± 10.2 (SD) years (range: 36-85 years). Images were qualitatively and quantitatively analyzed with respect to imaging presentation.HCC presented as a single tumor in 13/21 patients (62%), with a mean longest diameter of 26.9 ± 20.2 (SD) mm (range: 12-88 mm); 17/30 HCC (57%) had a largest diameter20 mm. A signal drop between in- and out-of-phase T1-weighted MR images was observed in 16/30 HCC nodules (53%). All HCC nodules (30/30; 100%) showed hyperenhancement on arterial phase images and 12/30 HCC nodules (40%) did not show a wash-out on portal or delayed phase images. Encapsulation was observed in 18/30 HCC nodules (60%). MRI findings consistent with liver cirrhosis were present in 16/21 patients (76%).Our results show that 57% of HCC in NASH can present as a lesion smaller than 20 mm and 40% do not display wash-out. These results suggest that classical imaging criteria developed for noninvasive diagnosis of HCC should be applied with caution to HCC in patients with NASH.

Heterogeneity within a putative stem cell population presents a challenge for studies and applications of such cells. Cloning may provide a strategy for reducing heterogeneity. However, previous studies have the weakness in reliability of single-cell-origin of the colonies. The present study aims to apply an alternative method to obtain clonal dental pulp cells with increased reliability of single cell origin. Dental pulp cells were cultured from 13 human wisdom teeth. Primary cultures of 3 human benign tumors were included as comparison. Cells were seeded into wells of a 96-plate at a mean density of 1 cell/well. On the next day, wells were inspected one by one to identify wells with single cells which were followed for 3 weeks. Survived clones were expanded and further characterized. Single cells were observed in all cases, the number of single-cell-wells varied from 16 to 33. Three weeks later, survived and grown clonal cells were observed in 10 to 29 wells, giving surviving rates of 33-91%. By contrast, though single tumor cells were also observed, none of them survived. Expanded clones exhibited diversity in viability and osteogenic differentiation which also differed from their parental cells. Seeding cells at clonal density into physically separated compartments like wells in a 96 plate and comprehensive observation provides a practical strategy for increasing reliability of single-cell origin of clonal cells. Cellular heterogeneity seems to be an intrinsic feature of dental pulp cells.

Nanobiomaterials have attracted tremendous attention in the biomedical field. Especially in the past few years, a large number of low dimensional nanobiomaterials, including 0D nanostructures, 1D nanotubes and 2D nanosheets, were employed for tumor therapy due to their optically triggered tumor therapy effects and drug loading capacities. However, these low dimensional nanobiomaterials cannot support cell adhesion and possess poor tissue regeneration ability, thus they are not suitable for application in regenerative medicine. Three dimensional (3D) nanofiber scaffolds have attracted extensive attention in tissue regeneration, including bone, skin, nerve and cardiac tissues, due to their similar extracellular matrix structures. Additionally, many 3D scaffolds displayed bone and cartilage regeneration abilities. Therefore, to obtain materials with both tumor therapy and tissue regeneration abilities, it is meaningful and necessary to develop 3D nanobiomaterials with multifunctions. In this review, we systematically review the research progress of nanobiomaterials with varied dimensional structures including 0D, 1D, 2D and 3D, as well as evolutional functions from single tumor therapy to simultaneous tumor therapy and tissue regeneration. This review may pave the way for developing an interdisciplinary research of nanobiomaterials in combination of tumor therapy and regenerative medicine.

Precision oncology relies on the identification of molecular alterations, responsible for tumor initiation and growth, which are suitable targets of specific inhibitors. The development of FGFR inhibitors represents an edifying example of the rapid evolution in the field of targeted oncology, with 10 different FGFR tyrosine kinase inhibitors actually under clinical investigation. In parallel, the discovery of FGFR activating molecular alterations (mainly FGFR3 mutations and FGFR2 fusions) across many tumor types, especially urothelial carcinomas and intrahepatic cholangiocarcinomas, widens the selection of patients that might benefit from selective FGFR inhibitors. The ongoing concomitant clinical evaluation of selective FGFR inhibitors in molecularly selected solid tumors brings new hopes for patients with metastatic cancer, for tumors so far excluded from molecularly guided treatments. Matching molecularly selected tumors with selective FGFR inhibitors has indeed led to promising results in phase I and II trials, justifying their registration to be expected in a near future, such as the recent accelerated approval of erdafitinib granted by the FDA for urothelial cancer. Widening our knowledge of the activity, efficacy, and toxicities relative to the selective FGFR tyrosine kinase inhibitors under clinical investigation, according to the exact FGFR molecular alteration, will be crucial to determine the optimal therapeutic strategy for patients suffering from FGFR-driven tumors. Similarly, identifying with appropriate molecular diagnostic, every single tumor harboring targetable FGFR alterations will be of utmost importance to attain the best outcomes for patients with FGFR-driven cancer.

Because of its multifactorial nature, predicting the presence of cancer using a single biomarker is difficult. We aimed to establish a novel machine-learning model for predicting hepatocellular carcinoma (HCC) using real-world data obtained during clinical practice. To establish a predictive model, we developed a machine-learning framework which developed optimized classifiers and their respective hyperparameter, depending on the nature of the data, using a grid-search method. We applied the current framework to 539 and 1043 patients with and without HCC to develop a predictive model for the diagnosis of HCC. Using the optimal hyperparameter, gradient boosting provided the highest predictive accuracy for the presence of HCC (87.34%) and produced an area under the curve (AUC) of 0.940. Using cut-offs of 200 ng/mL for AFP, 40 mAu/mL for DCP, and 15% for AFP-L3, the accuracies of AFP, DCP, and AFP-L3 for predicting HCC were 70.67% (AUC, 0.766), 74.91% (AUC, 0.644), and 71.05% (AUC, 0.683), respectively. A novel predictive model using a machine-learning approach reduced the misclassification rate by about half compared with a single tumor marker. The framework used in the current study can be applied to various kinds of data, thus potentially become a translational mechanism between academic research and clinical practice.

Prediction of prognosis of hepatocellular carcinoma (HCC) has shown an important role in improving treatment outcomes and preventing disease progression, however, the prognostic indicator of HCC is still lacking. The purpose of this study is to investigate the predictive value of GLR (gamma-glutamyl transpeptidase to lymphocyte count ratio) in single HCC with a tumor size (TS) ≤ 5 cm. A retrospective analysis was performed on 272 patients with TS ≤ 5 cm who underwent radical resection. The Pearson χ2 test was applied to discuss the relationship between HCC and GLR, alpha-fetoprotein (AFP). Then univariate and multivariate analysis was utilized to predict the risk factors for survival prognosis in patients. In this study, GLR showed a positive relation with tumor size, tumor-node-metastasis (TNM) stage, microvascular invasion, early recurrence, and serum aspartate aminotransferase (AST) level, while the AFP value only correlated with drinking. Elevated GLR value had poor overall survival (OS) and progression-free survival (PFS) of TS ≤ 5 cm HCC patients, GLR level and tumor size were closely related to the prognosis of small HCC patients compared with AFP. GLR may serve as a prognostic marker for dynamic monitoring of HCC patients with single TS ≤ 5 cm after radical resection.

Background: Although evidence for the application of albumin–bilirubin (ALBI) grading system to assess liver function in hepatocellular carcinoma (HCC) is available, less is known whether it can be applied to determine the prognosis of single HCC with different tumor sizes. This study aimed to address this gap.Methods: Here, we enrolled patients who underwent hepatectomy due to single HCC from the year 2010 to 2014. Analyses were performed to test the potential of ALBI grading system to monitor the long-term survival of single HCC subjects with varying tumor sizes.Results: Overall, 265 participants were recruited. The overall survival (OS) among patients whose tumors were ≤ 7 cm was remarkably higher compared to those whose tumors were > 7 cm. The Cox proportional hazards regression model identified the tumor differentiation grade, ALBI grade, and maximum tumor size as key determinants of the OS. The ALBI grade could stratify the patients who had a single tumor ≤ 7 cm into two distinct groups with different prognoses. The OS between ALBI grades 1 and 2 was comparable for patients who had a single tumor > 7 cm.Conclusions: We show that ALBI grading system can predict disease outcomes of single HCC patients with tumor size ≤ 7 cm. However, the ALBI grade may not predict capability the prognosis of patients with single tumor > 7 cm.

The intraperitoneal (IP) administration of chemotherapy is an alternative treatment for peritoneal carcinomatosis, allowing for higher intratumor concentrations of the cytotoxic agent compared to intravenous administration. Nevertheless, drug penetration depths are still limited to a few millimeters. It is thus necessary to better understand the limiting factors behind this poor penetration in order to improve IP chemotherapy delivery. By developing a three-dimensional computational fluid dynamics (CFD) model for drug penetration in a tumor nodule, we investigated the impact of a number of key parameters on the drug transport and penetration depth during IP chemotherapy. Overall, smaller tumors showed better penetration than larger ones, which could be attributed to the lower IFP in smaller tumors. Furthermore, the model demonstrated large improvements in penetration depth by subjecting the tumor nodules to vascular normalization therapy, and illustrated the importance of the drug that is used for therapy. Explicitly modeling the necrotic core had a limited effect on the simulated penetration. Similarly, the penetration depth remained virtually constant when the Darcy permeability of the tissue changed. Our findings illustrate that the developed parametrical CFD model is a powerful tool providing more insight in the drug transport and penetration during IP chemotherapy.

Bone and soft-tissue tumors are in general rare. Diagnosing these tumors is challenging based on the significant number of different tumor entities, the rareness of these tumors, and the considerable morphological heterogeneity which can be found within a single tumor entity. Considering that more than half of the described soft-tissue tumors and approximately 25% of the bone tumors harbor recurrent genetic alterations, the use of auxiliary molecular examinations should be strongly considered. Molecular analyses are important to confirm the diagnosis, to guide treatment, to provide information about prognosis, and to allow patient recruitment for basket trials based on the molecular signature of a tumor. In addition, novel molecular alterations detected by next-generation sequencing (NGS) obtain further insights into the pathogenesis of these rare tumors and allow a more detailed genetic classification. Based on our single-center results of NGS using the Ion AmpliSeq Cancer Hotspot Panel v2 and the Ion AmpliSeq Comprehensive Cancer Panel (Thermo Fisher Scientific) for mutational analyses as well as the Archer FusionPlex Sarcoma Kit (ArcherDX, Inc) to detect gene fusions in 26 genes since early 2016, we have experienced NGS as a very sensitive method to detect genetic alterations. In our experience, the use of the Archer FusionPlex Sarcoma Kit is superior to fluorescent in situ hybridization as an auxiliary tool in the routine workup of soft-tissue and bone tumors.