Number Of Tumor Lesions Research Articles

CK19 is associated with poor survival in patients with dual-phenotype hepatocellular carcinoma

Objective: To study the role of CK19 in the survival of patients diagnosed with DPHCC in Fujian, China, which has a high incidence of hepatocellular carcinoma (HCC). Methods: Patients with DPHCC (n=84) who had undergone surgical interventions at the 900th Hospital of Joint Logistic Support Force between 2013 and 2019 were retrospectively analyzed using the log-rank test and Kaplan-Meier method. Univariate and multivariate Cox model analyses were also conducted to further understand the correlation between CK19 and patient survival. Results: (1)Tumor size, differentiation, peripheral hepatic fibrosis, liver capsule invasion, microvascular invasion (MVI) and serum CA-199 level showed a correlation with CK19, as per the outcomes of Chi-squared tests. (2)According to the univariate analysis, the expression of CK19, MVI, the number of tumor lesions, necrosis, differentiation, peripheral hepatic fibrosis, and serum levels of both alpha-fetoprotein (AFP) and CA-199 showed a strong correlation with overall survival. (3)Necrosis and serum AFP levels were strongly related to an increased risk of death, according to the multivariate analysis. Conclusions: The expression of CK19 may correlate with the survival of patients with DPHCC and could potentially serve as a prognostic predictor of survival.

Study on the Expression, Prognosis, and Clinical Features of HOXA6 in Liver Cancer

Objective: To study and analyze the expression level of homeobox A6 (HOXA6) in patients with liver cancer and its correlation with prognosis. Methods: From January 2020 to July 2021, 43 patients with liver cancer who underwent surgery without prior radiotherapy or chemotherapy were selected. Liver cancer tissues and adjacent tissues were collected, and the expression levels of HOXA6 mRNA and protein were measured using RT-qPCR and Western blot. The expression level of HOXA6 in tumor tissues (without radiotherapy and chemotherapy) was compared with that in adjacent tissues. Additionally, the prognosis and clinical characteristics of patients with low HOXA6 expression were compared to those with high HOXA6 expression, and the factors influencing high HOXA6 expression in liver cancer patients were analyzed. Results: HOXA6 mRNA and protein expression levels in tumor tissues were significantly higher than in adjacent tissues (P < 0.05). There was no significant difference in the 1-year and 2-year survival rates between the high HOXA6 expression group and the low HOXA6 expression group (P > 0.05). However, the 3-year survival rate was lower in the high HOXA6 expression group compared to the low HOXA6 expression group (P < 0.05). There were no statistically significant differences between the two groups in terms of gender, age, tumor diameter, alpha-fetoprotein levels, or hepatitis B virus DNA levels (P > 0.05). However, significant differences were found in the number of tumor lesions, degree of differentiation, and the proportion of tumor metastasis between the two groups (P < 0.05). Multivariate logistic regression analysis revealed that the number of tumor lesions, degree of differentiation, and tumor metastasis were influencing factors for high HOXA6 expression in liver cancer patients (P < 0.05). Conclusion: HOXA6 expression levels are abnormally elevated in liver cancer patients, and higher HOXA6 expression is associated with a worse 3-year survival rate. The factors influencing HOXA6 expression include the number of tumor lesions, degree of differentiation, and tumor metastasis.

Impact of different parametric Patlak imaging approaches and comparison with a 2-tissue compartment pharmacokinetic model with a long axial field-of-view (LAFOV) PET/CT in oncological patients.

The recently introduced Long-Axial-Field-of-View (LAFOV) PET-CT scanners allow for the first-time whole-body dynamic- and parametric imaging. Primary aim of this study was the comparison of direct and indirect Patlak imaging as well as the comparison of different time frames for Patlak calculation with the LAFOV PET-CT in oncological patients. Secondary aims of the study were lesion detectability and comparison of Patlak analysis with a two-tissue-compartment model (2TCM). 50 oncological patients with 346 tumor lesions were enrolled in the study. All patients underwent [18F]FDG PET/CT (skull to upper thigh). Here, the Image-Derived-Input-Function) (IDIF) from the descending aorta was used as the exclusive input function. Four sets of images have been reviewed visually and evaluated quantitatively using the target-to-background (TBR) and contrast-to-noise ratio (CNR): short-time (30min)-direct (STD) Patlak Ki, short-time (30min)-indirect (STI) Patlak Ki, long-time (59.25min)-indirect (LTI) Patlak Ki, and 50-60min SUV (sumSUV). VOI-based 2TCM was used for the evaluation of tumor lesions and normal tissues and compared with the results of Patlak model. No significant differences were observed between the four approaches regarding the number of tumor lesions. However, we found three discordant results: a true positive liver lesion in all Patlak Ki images, a false positive liver lesion delineated only in LTI Ki which was a hemangioma according to MRI and a true negative example in a patient with an atelectasis next to a lung tumor. STD, STI and LTI Ki images had superior TBR in comparison with sumSUV images (2.9-, 3.3- and 4.3-fold higher respectively). TBR of LTI Ki were significantly higher than STD Ki. VOI-based k3 showed a 21-fold higher TBR than sumSUV. Parameters of different models vary in their differential capability between tumor lesions and normal tissue like Patlak Ki which was better in normal lung and 2TCM k3 which was better in normal liver. 2TCM Ki revealed the highest correlation (r = 0.95) with the LTI Patlak Ki in tumor lesions group and demonstrated the highest correlation with the STD Patlak Ki in all tissues group and normal tissues group (r = 0.93 and r = 0.74 respectively). Dynamic [18F]-FDG with the new LAFOV PET/CT scanner produces Patlak Ki images with better lesion contrast than SUV images, but does not increase the lesion detection rate. The time window used for Patlak imaging plays a more important role than the direct or indirect method. A combination of different models, like Patlak and 2TCM may be helpful in parametric imaging to obtain the best TBR in the whole body in future.

The efficacy of immune checkpoint inhibitors in patients with cancer with pseudoprogression.

2620 Background: Pseudoprogression (PsP) is quite a common phenomenon in cancer patients undergoing therapy with immune checkpoint inhibitors (ICI). It could be defined as temporary increase of tumor volume or the number of tumor lesions after beginning of ICI treatment (immune unconfirmed progressive disease - iUPD) followed by clinical response. However, many specialists in real clinical practice are hesitant to continue ICI therapy in patients with iUPD because of medical or financial constraints. We aimed to evaluate the efficacy of ICI in patients with clinical evidence of PsP. Methods: We retrospectively analyzed 1001 cases of ICI treatment (male 58,4%, age 28-90 years) in patients with various solid malignancies: melanoma – 316, lung – 280, kidney – 247, GI cancer – 96, cervix of the uteri – 62. The patients were treated in 2 regional referral centers in Moscow and Moscow Region between June 2018 and Dec. 2022. Unconfirmed progressive disease (iUPD) according to iRECIST criteria was diagnosed in 316 patients at the first imaging control after the beginning of ICI treatment (31,6%). Results: Among 316 patients with iUPD the presence of progression (immune confirmed progressive disease – iCPD) was verified in 105 (33,2%): melanoma – 109 (34,5%), lung – 86 (30,7%), kidney – 75 (30,4%), GI cancer – 42 (43,8%), cervix of the uteri – 4 (6,5%). Stable disease was found in 144 (45,6%), partial response in 50 (15,8% - iPR), complete response in 17 patients (5,4% - iCR). Altogether, PsP was diagnosed in 211 of 1001 patients (21,1%). Overall objective response rate in 316 patients with iUPD reached 21,2%, control over disease was achieved in 66,8% of cases. Severe immune-mediated adverse events (3-4 st. according to CTC AE 5.0) were diagnosed in 9 patients (2,8%). Median overall survival in patients with iUPD and ORR was 60,65 mon (95%CI 57,54-63,76), in patients without iUPD and ORR – 147,56 mon (95%CI 137,2-157,93). Conclusions: PsP was diagnosed in 21,1% of patients getting ICI treatment in real clinical practice with median survival in PsP patients with objective response of about 60 months. Only 10,5% of patients had iCPD after their second follow-up. We feel that close adherence to iRECIST criteria to verify true progression is mandatory in patients under ICI treatment to exclude unnecessary cessation of treatment.

A RARE UTERINE TUMOR: DISSEMINATED PERITONEAL LEIOMYOMATOSIS. CLINICAL OBSERVATIONS.

Disseminated peritoneal leiomyomatosis (DPL) is an extremely rare benign disease characterized by widespread lesions of the abdominal cavity, pelvis, and retroperitoneal space with tumor nodules of varying size and number, which are benign neoplasms consisting of smooth muscle fibers in their histological structure. To analyze clinical cases of DPL with a concise review of the current state of the DPL diagnosis and treatment. We analyzed 5 clinical cases of DPL of female patients aged 39-50 years (mean age 46.2 years) who underwent surgical treatment at the National Cancer Institute from 2010 to 2021. In all 5 patients, the diagnosis of DPL (8898/1) was verified according to pathological (using routine hematoxylin/eosin staining) and immunohistochemical (IHC) studies. All patients underwent surgical treatment with a laparotomy approach, the extent and radicality of which depended on the location and number of tumor lesions. At the time of follow-up, all 5 patients were alive and did not receive any special oncological treatment. DPL is characterized by a variety of clinical manifestations from polyserositis to acute abdomen, depending on the location and size of the main tumor focus. IHC analysis is the criterion for the final diagnosis, and radical removal of all tumor foci provides the best therapeutic prognosis. The treatment should be carried out in highly specialized cancer centers where surgeons have gained sufficient experience in performing cytoreductive surgery.

Clinical value of Cyclin D1 and P21 in the differential diagnosis of papillary thyroid carcinoma

BackgroundWith the continuous discovery of new borderline thyroid lesions and benign and malignant “gray areas”, coupled with the limitations of traditional immune indicators, the differential diagnosis of papillary thyroid carcinoma (PTC) has become more difficult. Cyclin D1 and P21 are cell cycle regulators involved in the occurrence and metastasis of multiple tumors, including PTC, but their specific functions are unclear.MethodsIn our study, immunohistochemical staining was used to explore the expression of Cyclin D1 and P21 in PTC, paracancerous tissue, follicular adenoma (FA) and papillary thyroid hyperplasia. In addition, their relationship with the clinicopathological features of PTC and their differential diagnostic value in distinguishing between intralymph node PTC metastases and intralymph node ectopic thyroid tissue were studied.ResultsAmong 200 primary PTC lesions, Cyclin D1 and P21 were found to be expressed in 186 (93.00%) and 177 (88.50%), respectively, and their expression levels were significantly higher in PTC tissue than in adjacent tissue, FA tissue and papillary thyroid hyperplasia tissue (P < 0.05). The expression levels of Cyclin D1 and P21 were positively correlated with tumor size and lymph node metastasis (P < 0.05) but not with sex, age, number of tumor lesions, histological subtype, chronic lymphocytic thyroiditis or TNM stage (P < 0.05). The expression levels of Cyclin D1 and P21 were significantly correlated (P < 0.05). The positivity rates of Cyclin D1 and P21 in intralymph node PTC metastases were 97.96% (48/49) and 89.80% (44/49), respectively, which were significantly higher than those in intralymph node ectopic thyroid tissue (P < 0.05). The sensitivity (Se) and negative predictive value (NPV) of Cyclin D1 and P21 detection alone or in combination were higher than those of the combined detection of the classical antibody markers CK19, HBME-1 and Galectin-3. Besides, the Se, Sp, PPV and NPV of Cyclin D1 and P21 in differentiating intralymph node PTC metastases and intralymph node ectopic thyroid tissue were higher.ConclusionsThe results of our study show that Cyclin D1 and P21 are highly sensitive and specific markers for the diagnosis of PTC that are superior to traditional classical antibodies. And, these two markers are of great value in the differential diagnosis of intralymph node PTC metastases and intralymph node ectopic thyroid tissue.

Microvascular invasion is associated with poor survival in patients with dual-phenotype hepatocellular carcinoma.

Microvascular invasion (MVI) has previously been reported to be related to cancer prognosis; however, its significance in patients with dual-phenotype hepatocellular carcinoma (DPHCC) remains uncharacterized. We studied the role of MVI in the survival of patients diagnosed with DPHCC in Fujian, China, which has a high incidence of HCC. Patients with DPHCC (n = 84) who had undergone surgical interventions at the 900th Hospital of the Joint Logistic Support Force between 2013 and 2019 were retrospectively analyzed using the log-rank test and Kaplan-Meier method. Univariate and multivariate Cox model analyses were also conducted to further understand the correlation between MVI and patient survival. Our results indicated that MVI was related to poor survival. According to the univariate analysis, MVI, the number of tumor lesions, necrosis, differentiation, peripheral hepatic fibrosis, the expression of cytokeratin 19 (CK19), and serum levels of both ɑ-fetoprotein (AFP) and cancer antigen-199 showed a strong correlation with overall survival. Necrosis and serum AFP levels were strongly related to an increased risk of death, according to the multivariate analysis. Tumor size; the number of tumor lesions; differentiation; peripheral hepatic fibrosis; liver capsule invasion; and expression of CK19, vascular endothelial growth factor, CK7, and mucin 1 showed a correlation with MVI, per the outcomes of χ2 tests. Microvascular invasion may correlate with the survival of patients with DPHCC and could potentially serve as a prognostic predictor of survival.

Comparison between En bloc Resection and Conventional Resection of Bladder Tumor in Perioperative and Oncological Outcomes

Abstract Purpose: Conventional transurethral resection of bladder tumors (cTURBT) has been the main technique for treating visible bladder tumor for decades. However, the reported rate of detrusor muscle presence in cTURBT specimen was lower than 80%, which is associated with imprecise staging and poor prognosis. Here, we present a retrospective analysis to compare the detrusor muscle detection rate and outcomes between en bloc resection of bladder tumor (ERBT) and cTURBT. Materials and Methods: Between January 2016 and December 2019, a total of 150 procedures performed by single surgeon in single institute were reviewed in this study. Of these procedures, 41 (27.3%) were ERBT and 109 (72.6%) were cTURBT. The two techniques were compared for pathological detrusor muscle detection, history of upper tract urothelial cancer, number of tumor lesions, histopathological grading and staging, time of operation, and time of catheterization and hospitalization. Results: The muscularis propria detection rate was statistically significantly higher in the ERBT group than in the cTURBT group (82.9% vs. 43.1%, P &lt; 0.0001). The multivariate analysis showed resection method as an independent factor of detrusor muscle presentation (P &lt; 0.0001). The mean Foley catheter indwelling and hospitalization days were longer in the ERBT group but were only 1 day longer than in the cTURBT group. Conclusion: ERBT significantly increases the muscularis propria detection rate than cTURBT. ERBT can provide more accurate cancer staging and contribute to proper decision-making. This study strengthens ERBT as a feasible and promising management of bladder cancer.

Comparison of Efficacy and Safety of TACE Combined with Microwave Ablation and TACE Combined with Cryoablation in the Treatment of Large Hepatocellular Carcinoma

Purpose To retrospectively evaluate the efficacy and safety of TACE combined with microwave ablation (MWA) and TACE combined with cryoablation (CRA) in the treatment of large hepatocellular carcinoma. Methods A retrospective analysis was performed on 81 patients with large hepatocellular carcinoma (tumor diameter 5～8 cm cm) who received TACE combined with ablation in our hospital from February 2015 to February 2019. The study patients were divided into TACE combined with MWA group (T-MWA, n = 41) and TACE combined with CRA group (T-CRA, n = 40) according to the treatment plan. Overall survival (OS) and progress free survival (PFS) were compared between the two groups, and complications were observed. Survival curves for OS and PFS were constructed by the Kaplan–Meier method. Differences in overall survival were compared using the log-rank test. Results There was no statistical difference in general conditions between the two groups of patients. The results showed that 30 (73.2%) patients in T-MWA group achieved objective response (OR) and 39 (95.1%) patients achieved disease control (DC), compared with 24 (60.0%) patients in T-CRA group who achieved objective response (OR) and 37 (92.5%) patients who achieved disease control (DC). The median OS was 19.2 months in the T-MWA group and 18.6 months in the T-CRA group (P=0.64). The median PFS was 9.3 months in the T-MWA group and 12.3 months in the T-CRA group (P=0.6). Univariate and multivariate analysis showed that portal vein tumor thrombus (PVTT), intrahepatic tumor diameter, and the number of tumor lesions were common prognostic factors for OS and PFS. In terms of surgery-related complications and adverse reactions, abdominal pain and gastrointestinal reactions were observed in 13 (31.7%) and 11(26.8%) cases in the T-MWA group, while we observed 4 (10.0%) and 2 (5.0%) cases in the T-CRA group, respectively. The difference between the two was statistically significant (P < 0.05). Conclusion TACE combined with MWA and TACE combined with CRA were equally effective in the treatment of large hepatocellular carcinoma. TACE-CRA can effectively reduce the incidence of abdominal pain and gastrointestinal reactions in patients. However, compared with TACE-MWA, TACE-CRA is more likely to cause thrombocytopenia.

A CT-Based Radiomic Signature Can Be Prognostic for 10-Months Overall Survival in Metastatic Tumors Treated with Nivolumab: An Exploratory Study.

Baseline clinical prognostic factors for recurrent and/or metastatic (RM) head and neck squamous cell carcinoma (HNSCC) treated with immunotherapy are lacking. CT-based radiomics may provide additional prognostic information. A total of 85 patients with RM-HNSCC were enrolled for this study. For each tumor, radiomic features were extracted from the segmentation of the largest tumor mass. A pipeline including different feature selection steps was used to train a radiomic signature prognostic for 10-month overall survival (OS). Features were selected based on their stability to geometrical transformation of the segmentation (intraclass correlation coefficient, ICC > 0.75) and their predictive power (area under the curve, AUC > 0.7). The predictive model was developed using the least absolute shrinkage and selection operator (LASSO) in combination with the support vector machine. The model was developed based on the first 68 enrolled patients and tested on the last 17 patients. Classification performance of the radiomic risk was evaluated accuracy and the AUC. The same metrics were computed for some baseline predictors used in clinical practice (volume of largest lesion, total tumor volume, number of tumor lesions, number of affected organs, performance status). The AUC in the test set was 0.67, while accuracy was 0.82. The performance of the radiomic score was higher than the one obtainable with the clinical variables (largest lesion volume: accuracy 0.59, AUC = 0.55; number of tumoral lesions: accuracy 0.71, AUC 0.36; number of affected organs: accuracy 0.47; AUC 0.42; total tumor volume: accuracy 0.59, AUC 0.53; performance status: accuracy 0.41, AUC = 0.47). Radiomics may provide additional baseline prognostic value compared to the variables used in clinical practice.

18F-FDG PET/CT Scans Can Identify Sub-Groups of NSCLC Patients with High Glucose Uptake in the Majority of Their Tumor Lesions.

Background: Reprogrammed glucose metabolism is a hallmark of cancer making it an attractive therapeutic target, especially in cancers with high glucose uptake such as non-small cell lung cancer (NSCLC). Tools to select patients with high glucose uptake in the majority of tumor lesions are essential in the development of anti-cancer drugs targeting glucose metabolism. Type 2 diabetes mellitus (T2DM) patients may have tumors highly dependent on glucose uptake. Surprisingly, this has not been systematically studied. Therefore, we aimed to determine which patient and tumor characteristics, including concurrent T2DM, are related to high glucose uptake in the majority of tumor lesions in NSCLC patients as measured by 2-deoxy-2-[fluorine-18]fluoro-D-glucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) scans.Methods: Routine primary diagnostic 18F-FDG PET/CT scans of consecutive NSCLC patients were included. Mean standardized uptake value (SUVmean) of 18F-FDG was determined for all evaluable tumor lesions and corrected for serum glucose levels according to the European Association of Nuclear Medicine Research Ltd guidelines. Patient characteristics potentially determining degree of tumor lesion glucose uptake in the majority of tumor lesions per patient were investigated.Results: The cohort consisted of 102 patients, 28 with T2DM and 74 without T2DM. The median SUVmean per patient ranged from 0.8 to 35.2 (median 4.2). T2DM patients had higher median glucose uptake in individual tumor lesions and per patient compared to non-diabetic NSCLC patients (SUVmean 4.3 vs 2.8, P < 0.001 and SUVmean 5.4 vs 3.7, P = 0.009, respectively). However, in multivariable analysis, high tumor lesion glucose uptake was only independently determined by number of tumor lesions ≥1 mL per patient (odds ratio 0.8, 95% confidence interval 0.7-0.9).Conclusions: 18F-FDG PET/CT scans can identify sub-groups of NSCLC patients with high glucose uptake in the majority of their tumor lesions. T2DM patients had higher tumor lesion glucose uptake than non-diabetic patients. However, this was not independent of other factors such as the histological subtype and number of tumor lesions per patient.

Management and prognostic analysis of patients with gestational trophoblastic neoplasia (GTN) in FIGO stage IV and its special type

GTN is a group malignant diseases from placental trophoblastic cells. There are very few cases of GTN with FIGO (International Federation of Gynecology and Obstetrics) stage IV all over the world, and the special types (patients with metastatic lesions and with no evidence of GTN neither in genitalia nor in lungs) have rarely been reported. It is necessary to conduct large retrospective studies aimed at exploring the diagnosis, treatment and outcomes of this disease. In this retrospective study, 716 patients with GTN were treated at Zhejiang University School of Medicine Women’s Hospital between January 1999 and September 2019; 26 patients were diagnosed as stage IV GTN; Among the 26 stage IV GTN patients, 5 were defined as the special types. The 5-year OS rate of the total 26 FIGO stage IV GTN patients was 69.0%. There was no significant difference of survival rate between stage IV GTN and its special type. And no significant differences in blood type, antecedent pregnancy type, the interval from last known pregnancy, pretreatment serum HCG (human chorionic gonadotropin) level, maximum diameter of tumors, FIGO score, underwent surgery or not and pathological pattern by the outcomes. Age, number of tumor lesions, primary chemotherapy regimen was EMA-CO or EP-EMA protocol and chemoresponse affected the prognosis significantly. Only number of tumor lesions > 8 was independent prognostic factors associated with poorer OS.

The Association of Serum Estradiol Level with the Susceptibility and Clinicopathological Features of Hepatocellular Carcinoma in Patients with Nonalcoholic Fatty Liver Disease

Abstract Background: Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. The most common underlying causes of Hepatocellular car-cinoma (HCC) are chronic liver diseases and cirrhosis. Aim of Study: Our study aimed to investigate the serum estradiol levels in patients with nonalcoholics steatohepatitis (NASH) related HCC and to explore their correlations with clinicopathological features of HCC. Patients and Methods: A Controlled Cross-Sectional Study included 200 patients with NAFLD (181 patients with NAFLD and 23 patients with NAFLD related HCC) and 50 controls. Serum estradiol was measured by enzyme-linked immuno-sorbent assay (ELISA). Results: The serum level of estradiol was significantly lowered in patients with NAFLD (32.24±7.3pg/ml) compared to controls (42.9±3.9pg/ml). Moreover, our findings revealed lower concentrations of serum estradiol in the HCC group (28.6±5.3pg/ml) compared to the NAFLD group (33.45 ±4.3pg/ml, p<0.00 1). We found significant negative correla-tions between serum estradiol levels and clinicopathological features of HCC (portal vein thrombosis, lymph node metas-tasis, number of tumor lesions, advanced clinical stage, tumor size, tumor site, distant metastasis) in patients with NAFLD complicated with HCC. linear regression test and we observed that serum triglycerides and a-fetoprotein were significantly associated with serum estradiol among the HCC group. Conclusion: Serum estradiol level was significantly low-ered in the HCC subgroup compared to the NAFLD group and negatively correlated with clinicopathological features of HCC. Serum estradiol can be used as a promising predictor of HCC in female patients with NAFLD.

Analysis of prognostic factors of more/equal to10\xa0years of survival for liver cancer patients after liver transplantation

ObjectiveTo investigate prognostic factors of more than 10 years of survival for liver cancer patients after liver transplantation.MethodsFrom May 2000 to May 2007, a total of 134 liver cancer patients who underwent liver transplantation in the Department of Hepatobiliary Surgery, Peking University People’s Hospital, were continuously and retrospectively enrolled. The patients included 120 males and 14 females. There were 124 cases (92.5%) of primary hepatocellular carcinoma, 9 cases (6.7%) of cholangiocarcinoma, and 1 case of mixed hepatocellular carcinoma and cholangiocarcinoma. Patients with perioperative death were excluded. Follow-up was performed until May 31st, 2017 or the time of death. According to the data on postoperative survival time, patients were divided into a < 10 years group (81 cases) and a ≥ 10 years group (53 cases). Patients’ clinical data were recorded and analyzed, including alpha-fetoprotein (AFP) level (≥ 400 µg/L or < 400 µg/L), number of tumor lesions (< 3 or ≥ 3), tumor size (≤ 5 cm or > 5 cm), vascular tumor thrombus (large blood vessel or non-large blood vessel), and histological differentiation degree. The Kaplan–Meier method was used to calculate survival rates. The log-rank method was used to compare the differences between survival curves. The Cox proportional hazards regression model was used to perform multivariate analyses of possibly influential factors.Results(1) Follow-up was conducted with all 134 liver cancer patients after liver transplantation. The follow-up periods were 1–201 months, with a median of 18 (8.75, 132.5) months. The Kaplan–Meier survival analysis results showed that the 1-year, 3-year, 5-year, and 10-year cumulative survival rates were 70.3%, 48.6%, 46.8%, and 46.8%, respectively. (2) The differences in the age of patients, the incidence rate of AFP ≥ 400 µg/L, tumor histological differentiation, vascular tumor thrombi, tumor lesion size, and number of tumor lesions between two groups were all statistically significant (all P < 0.01). (3) The cumulative survival rates were different in AFP (log-rank χ2 = 13.428), histopathologic differentiation (log-rank χ2 = 33.592), large blood vessel tumor thrombi (log-rank χ2 = 36.470), tumor lesion size (log-rank χ2 = 39.835), and number of tumor lesions (log-rank χ2 = 47.016), and there were statistically significant differences between groups (all P < 0.01). (4) Multivariate Cox proportional hazards regression analyses showed that ≥ 3 tumor lesions [hazard ratio (HR) = 2.879, 95% confidence interval (CI) 1.566–5.422], tumor lesion size > 5 cm (HR = 2.682, 95% CI 1.382–5.366), large blood vessel tumor thrombi (HR = 1.831, 95% CI 1.010–3.341), and poor histological differentiation (HR = 2.150, 95% CI 1.372–3.394), were risk factors affecting the 10-year survival of liver cancer patients after liver transplantation (all P < 0.05).ConclusionTumor size, tumor number, large blood vessel tumor thrombi, and low tumor differentiation were all found to be independent risk factors affecting the 10-year survival rate after liver transplantation in liver cancer patients.

CD133 expression and α-fetoprotein levels define novel prognostic subtypes of HBV-associated hepatocellular carcinoma: A long-term follow-up analysis.

Hepatocellular carcinoma (HCC) is a highly heterogeneous type of tumor, which may be caused by the stem/progenitor cell features of particular HCC cells. Recent studies have subclassified HCC into different prognostic subtypes according to just one stemness-associated marker. However, one stemness-associated marker is not sufficient to clearly define cancer stem cells, or to decipher the heterogeneous nature of HCC. For a more precise subtype classification for prognostic application, a combination of multiple stemness-associated markers is required. Cluster of differentiation 133 (CD133) and α-fetoprotein (AFP) are common stemness-associated markers for HCC that have not yet been employed for HCC subtype classification. In the present study, CD133 expression was assessed by immunohistochemistry in 127 hepatitis B virus-associated HCC tumor specimens. Based on CD133 immunostaining and serum AFP levels, the HCC cases were subclassified into four subtypes, which demonstrated different clinicopathological features and varying prognoses. Among the four subtypes, the number of tumor lesions, histological grade and vascular invasion were significantly different (P=0.002, P=0.018 and P=0.022, respectively). CD133+AFP+ HCC was associated with a relatively poor prognosis, CD133−AFP− HCC was associated with a relatively good prognosis, while CD133+AFP− HCC and CD133−AFP+ HCC were associated with an intermediate prognosis. These prognostic values were confirmed by borderline or statistical significance (between all groups, overall survival, P=0.061; recurrence-free survival, P=0.015). These results define a novel and simple system, based on CD133 and AFP, for classifying HCC into four distinct prognostic subtypes. This classification system may aid the assessment of patients with HCC for personalized therapy.

Experience in local Glyciphon chemotherapy of basal cell carcinoma of the problem face areas

Basal cell carcinoma (BCC) is the most common type of malignant skin tumors, characterized by selective localization on the head and neck. Currently there is a variety of treatment methods for this disease, but some of them are not feasible due to patients’ age, cancer localization, morphological type, size, or number of tumor lesions. In that respect, local chemotherapy of BCC, especially for the problem face areas, can serve as a good alternative. Clinical and experimental trials have shown a high treatment effect for 30 % Glyciphon ointment in patients with BCC. In this article we present successful examples of treatment of patients with BCC on the problem face areas using Glyciphon.

Chemo-immunotherapy induces tumor regression in a mouse model of spontaneous mammary carcinogenesis.

Tumor-specific immune tolerance represents an obstacle for the development of effective anti-tumor immune responses through cancer vaccines. We here evaluated the efficacy of chemo-immunotherapy in breaking tumor-specific immune tolerance in an almost incurable mouse model of spontaneous carcinogenesis.Transgenic HER-2/neu mice bearing large mammary tumors received the adoptive transfer of splenocytes and serum isolated from immune donors, with or without pre-conditioning with cyclophosphamide. Treatment efficacy was assessed by monitoring tumor growth by manual inspection and by magnetic resonance imaging. The same chemo-immunotherapy protocol was tested on tumor-free HER-2/neu mice, to evaluate the effects on tumor emergence.Our data show that chemo-immunotherapy hampered carcinogenesis and caused the regression of large mammary tumor lesions in tumor-bearing HER-2/neu mice. The complete eradication of a significant number of tumor lesions occurred only in mice receiving cyclophosphamide shortly before immunotherapy, and was associated with increased serum anti HER-2/p185 antibodies and tumor leukocyte infiltration. The same protocol significantly delayed the appearance of mammary tumors when administered to tumor-free HER-2/neu mice, indicating that this chemo-immunotherapy approach acted through the elicitation of an effective anti-tumor immune response. Overall, our data support the immune-modulatory role of chemotherapy in overcoming cancer immune tolerance when administered at lymphodepleting non-myeloablative doses shortly before transfer of antigen-specific immune cells and immunoglobulins. These findings open new perspectives on combining immune-modulatory chemotherapy and immunotherapy to overcome immune tolerance in cancer patients.

Abstract A82: Identification of NSCLC patients with high tumor glucose uptake by 18F-FDG-PET

Abstract Introduction: One of the hallmarks of cancer is reprogramming of energy metabolism whereby cancer cells become dependent on aerobic glycoysis, making high glucose uptake essential. To optimally utilize novel therapeutics targeting these processes, it is important to identify patients with tumors highly dependent on glucose uptake and to be informed about intra-patient heterogeneity. 2-deoxy-2-[fluorine-18]fluoro-D-glucose emission tomography (18F-FDG-PET) non-invasively visualizes whole body glucose uptake and could be used for this purpose. We aimed to identify a subset of non-small cell lung cancer (NSCLC) patients with high tumor glucose uptake using 18F-FDG-PET scans and to determine intra-patient heterogeneity and patient and tumor characteristics in this group. Methods: Primary diagnostic 18F-FDG-PET/CT scans of NSCLC patients were retrospectively selected from 2418 consecutive scans performed at the University Medical Center Groningen (UMCG) in 2013. Exclusion criteria were: another active malignancy and inadequate fasting prior to the scan. Included were 32 patients with concurrent type 2 diabetes mellitus (T2DM) and 32 consecutive eligible control patients. All 18F-FDG-PET/CT scans were performed and analyzed according to the European Association of Nuclear Medicine Research Ltd (EARL) accreditation standards ensuring standardized data collection. A region of interest (ROI) was drawn around each visible 18F-FDG avid tumor lesion, and in normal tissue: liver, heart, peripheral muscle and abdominal fat. Subsequently, for all ROIs, standardized uptake values (SUVs) mean 40% were determined. High tumor uptake was defined as a SUVmean &amp;gt;5 and very high tumor uptake as a SUVmean &amp;gt;8. The metabolic tumor burden was evaluated by determining whole body metabolic tumor volume (MTV), defined as the volume corresponding to regions in which the SUVmean was measured. The analysis of glucose uptake was only performed for lesions with a volume≥1 mL due to underestimation of SUV values in smaller lesions due to partial volume effects. IBM SPSS Statistics 22 was used for conducting the Chi-square tests. Results: 673 18F-FDG-PET avid lesions were analyzed in 64 patients. The mean age was 63 years, 63% was male, 56% had adeno- and 39% had squamous cell carcinoma histology. Median number of tumor lesions per patient was 3 (1-90). There was a large heterogeneity in tumor glucose uptake both within and between patients. The highest measured SUVmean was 15.8 and the lowest 0.5. In the patient with the highest heterogeneity the absolute difference between the highest and lowest measured SUVmean in tumor lesions was 14. In 8/64 patients all lesions were very highly active (SUVmean &amp;gt;8), in 14/64 patients more than half of the lesions were very highly active and 28/64 patients had at least one very highly active lesion. In 17/64 patients all lesions were highly active (SUVmean &amp;gt;5) and in 28/64 patients more than half of the lesions were highly active, this was more often the case in patients with T2DM (14/32 vs 3/32 p=0.002 and 19/32 vs 9/32 p=0.012 respectively) and more often the case in patients with squamous cell carcinoma (11/25 vs 4/36 p=0.003 and 15/25 vs 10/36 p=0.012). In 46/64 patients there was at least one highly active lesion. In 18/64 patients all lesions had a SUVmean≤5. The volume of each tumor lesion (lesion MTV) and whole body tumor volume (MTV) did not correlate with tumor glucose uptake as measured using 18F-FDG. Conclusion: In a significant subset of NSCLC patients the majority of lesions are highly metabolically active. These patients may be especially sensitive to drugs targeting glucose uptake or glycolysis. Citation Format: Anne M. Hendriks, Adrienne H. Brouwers, Joop D. Lefrandt, Wim J. Sluiter, Wim Timens, Harry J. M. Groen, Elisabeth G. E. de Vries, Mathilde Jalving. Identification of NSCLC patients with high tumor glucose uptake by 18F-FDG-PET. [abstract]. In: Proceedings of the AACR Special Conference: Metabolism and Cancer; Jun 7-10, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(1_Suppl):Abstract nr A82.

149 Intestinal Microbiota Defined by the Absence of the Triggering Receptor Expressed on Myeloid Cells Type-2 (TREM-2) Is Transmissible and Protects From Colitis Associated Cancer

BACKGROUND. Inflammatory bowel disease (IBD) represents a prototypic example of connection between inflammation and cancer. Severity, extent and duration of the disease represent the major risk factors related to colorectal cancer (CRC) development. Recently we have demonstrated that the absence of the bacterial sensor TREM-2 prevented acute and chronic colitis, reducing the levels of mucosal inflammatory cytokines and T-cell activation. However, whether TREM-2 plays also a role in regulating the composition of microbial communities or in colitis associated cancer (CAC) is unknown. METHODS. The carcinogen azoxymethane (AOM) with 3 cycles of dextran sulfate sodium (DSS) was used as CAC model. Gut microbiota composition was estimated by high-throughput 16S rRNA gene sequencing in fecal samples collected from TREM-2 knockout (KO) and wild-type (WT) littermates. The bacterial communities were assessed in healthy and tumor-bearing mice, evaluating their contribution in CAC development by co-housing experiments. TREM-2 expression was investigated by confocal microscopy and flow cytometry. Carcinogenesis was evaluated counting and grading the tumor lesions. Moreover, tumor proliferation was evaluated by BrdU+ cell count. Finally, TNF, IL-6, IL-23, TGF-β, iNOS and COX-2 mucosal levels were compared between KO and WT littermates. RESULTS. After CAC induction, confocal microscopy and FACS analysis revealed increased TREM-2 expression in CD11c+ dendritic cells surrounding tumor areas. Carcinogenesis was affected in the absence of TREM2, with a reduced number of tumor lesions that also possessed a low-grade and displayed a reduced proliferation. Interesting, co-housing experiments revealed that intestinal microbiota composition might be transmitted horizontally from TREM-2 KO to WT littermates decreasing significantly number (WT = 6±1, WT CH = 3±1, p < 0.05) and dimension (WT = 18.5±2.8 mm2, WT CH = 6.2±1.2 mm2, p < 0.01) of tumor lesions. In particular, both CAC induction and co-housing induced a redistribution of the relative abundance of Prevotellaceae (belonging to the phylum Bacteroidetes), Ruminococcaceae (Firmicutes) and Rikenellaceae (Bacteroidetes). Finally, at mucosal level, TREM-2 absence reduced the production of IL23 and IL-6, and down-regulated tumor promoting proteins such as iNOS and COX-2. CONCLUSIONS. Our findings reveal TREM-2 as a key component involved in controlling colon cancer development. In particular, TREM-2 expression is up-regulated during CAC by CD11c+ dendritic cells and its genetic deletion prevents tumor formation and proliferation. TREM-2 shapes gut microbiota composition and unveils a novel mechanism that could offer a new therapeutic target to prevent or treat intestinal inflammation and carcinogenesis.

Serum levels of preoperative α-fetoprotein and CA19-9 predict survival of hepatic carcinoma patients after liver transplantation

ObjectiveThe aim of this study was to assess serum levels of presurgical α-fetoprotein (AFP) and carbohydrate antigen 19-9 (CA19-9) as prognostic markers in patients with hepatic carcinoma after liver transplantation (LT).MethodsA total of 226 patients were recruited for the analysis of serum AFP and CA19-9 levels, on the basis of which the tumor marker type (TMT) was defined and evaluated for prognostic prediction. Overall survival (OS) and relapse-free survival (RFS) were analyzed using Kaplan–Meier curves, and univariate and multivariate Cox models.ResultsOne-year and 5-year OS were 79.0 and 58.0%, respectively, whereas RFS were 70.3 and 62.2%, respectively, in this cohort of patients. There were six variables predicting both OS and RFS, including TMT, tumor size, number of tumor lesions, extrahepatic or vascular invasion, and histopathological grade. Among these, TMT, tumor size, and extrahepatic invasion were all independent predictors of OS and RFS among these patients. Further, on the basis of TMT, novel LT selection criteria for patients with hepatic carcinoma, which supplemented the Milan criteria, were adopted, because the patients within the Milan criteria (n=107) and those exceeding Milan but fulfilling the proposed criteria (n=30) had similar 5-year OS (77.8 vs. 79.3%, P=0.862) and RFS (85.5 vs. 75.1%, P=0.210) rates.ConclusionThe data from this study showed that serum levels of preoperative AFP and CA19-9 were able to predict survival of patients with hepatic carcinoma after LT. This study included novel criteria, adding serum AFP and CA19-9 levels to the selection criteria for LT eligibility of patients, in addition to the Milan criteria.