Absence Of Vascular Invasion Research Articles

Longitudinal alterations in health-related quality of life and its impact on the clinical course of patients with advanced hepatocellular carcinoma receiving sorafenib treatment.

BackgroundThis study aimed to identify the health-related quality of life (HRQOL) domains associated with prognosis by assessing longitudinal alterations in HRQOL in patients with advanced hepatocellular carcinoma receiving sorafenib.MethodsWe prospectively assessed HRQOL by administering the SF-36 questionnaire 3-monthly to consecutive patients with advanced hepatocellular carcinoma receiving sorafenib. We evaluated the impact of HRQOL on their overall survival and duration of treatment with sorafenib using Cox's proportional hazards model.ResultsThere were 54 participants: 42 (78 %) were male, the median age was 71 years, 24 (44 %) had hepatitis C virus infection, 33 (61 %) had Child-Pugh scores of 5, and 30 (56 %) had TNM stage IV hepatocellular carcinoma. The median overall survival and treatment duration were 9 and 5 months, respectively, and 40 patients (74 %) died. Thirteen patients receiving sorafenib over a 1-year period maintained all domain scores >40, without a significant decline during the treatment period. In contrast, physical functioning, physical role, and vitality scores declined continuously and significantly in the year before death (in the 40 patients who died). Previous curative treatment and physical functioning scores ≥40 at baseline were significantly associated with longer overall survival by multivariate analysis. Social functioning scores ≥40, absence of vascular invasion, and lower DCP value were significant predictors of longer treatment duration.ConclusionsHRQOL was not significantly impaired in those patients who were able to complete a 1-year course of sorafenib treatment. Baseline physical functioning scores ≥40 and social functioning scores ≥40 were significantly associated with longer overall survival and longer treatment duration, respectively. Thus, HRQOL could be a valuable marker to predict the clinical course of patients with advanced hepatocellular carcinoma receiving sorafenib.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2908-7) contains supplementary material, which is available to authorized users.

Prognostic Factors in Non-Small Cell Lung Cancer Less Than 3 Centimeters: Actuarial Analysis, Accumulative Incidence and Risk Groups

IntroductionIn TNM classification, factors determining the tumor (T) component in non-small cell lung cancer have scarcely changed over time and are still based solely on anatomical features. Our objective was to study the influence of these and other morphopathological factors on survival. MethodsA total of 263 patients undergoing lung resection due to stage I non-small cell lung cancer ≤3cm in diameter were studied. A survival analysis and competing-risk estimate study was made on the basis of clinical, surgical, and pathological variables using actuarial analysis and accumulative incidence methods, respectively. A risk model was then generated from the results. ResultsSurvival at 5 and 10 years was 79.8 and 74.3%, respectively. The best prognostic factors were presence of symptoms, smoking habit and FEV1>60%, number of resected nodes>7, squamous histology, absence of vascular invasion, absence of visceral pleural invasion and presence of invasion more proximal than the lobar bronchus. All these were statistically significant according to the actuarial method. The factor “age<50 years” was close to the margin of statistical significance. Pleural invasion and vascular invasion were entered in the multivariate analysis. The competing-risk analysis showed a probability of death due to cancer of 14.3 and 35.1% at 5 and 10 years, respectively. Significant variables in the univariate and multivariate analyses were similar, with the exception of FEV1>60%. ConclusionsPleural invasion and vascular invasion determine survival or risk of death due to non-small cell lung cancer ≤3cm and can be used for generating a predictive risk model.

Abstract P1-15-06: Lobular histology and partial breast irradiation: To what extent is it a cautionary parameter?

Abstract Aim: The high likelihood of multicentricity and multifocality linked to lobular histology (ILC) has called into question the partial breast irradiation. Patients with ILC are categorized in the cautionary group according to ASTRO guidelines. We looked into the population treated with intraoperative radiotherapy with electrons (ELIOT) as full dose to investigate the impact of lobular compared to ductal histology (IDC) in terms of local recurrence. Matherials and methods: From 1999 to 2007, 2220 patients were treated with breast conserving surgery and intraoperatory radiotherapy with electrons ( 21 Gy at 90% isodose) as sole treatment. The study population includes both patients treated outside and inside the clinical randomized phase III trial ELIOT. Out of 2220 patients, 255 (11.5%) presented ILC. We compared this group with patients having IDC, treated in the same period. The rate of local recurrences has been analyzed, with a minimum follow-up of 5 years. The role of patients and tumor features on local control has been evaluated. Results: Compared to IDC group, patients with ILC were older (≥ 70, 20% vs. 11%), with no lymph node involvement( pN0, 79% vs. 70%), low grading( G1-2,86% vs.72%), absence of vascular invasion( 81% vs. 98%), higher hormonal receptor status (ER +, 97% vs. 88%), HER2 negativity (96% vs. 89%), low proliferative index( Ki-67, 23% vs. 44%). No differences were noticed with regard to the technical parameters of ELIOT. On the whole, the incidence of local relapse was 4.5% at 5 years (0.9/100 per year). Within the first 5 years of follow-up, no differences were observed between lobular and ductal histology, but after 5 years the difference became significant (p 0.05). Higher risk of local relapse was also observed in old patients ( over 60) with ILC. Regarding the biomolecular classification, lobular carcinomas belonging to Luminal A subtype had a more aggressive local behavior than Luminal A ductal carcinomas, showing a significantly higher rate of local relapse (p 0.0021). Conclusion: In spite of a favorable tumor profile, a greater incidence of local relapse occurred in tumors with ILC compared to ductal histology. When considering the anagraphic, histological and biomolecular variables, the old age (&amp;gt;60), the proliferative index and the luminal A subtype turned out to be significant. Interestingly, the incidence of local relapse becomes statistically significant 5 years after the treatment. This event points out the importance of an adequate follow-up length, especially in lobular histology for which other reports on whole breast irradiation in literature describe similar biological behavior . Citation Format: Maria Cristina Leonardi, Patrick Maisonneuve, Anna Morra, Nicole Rotmensz, Samantha Dicuonzo, Roberta Lazzari, Veronica Dell'acqua, Federica Cattani, Mauro Mastropasqua, Alberto Luini, Roberto Orecchia. Lobular histology and partial breast irradiation: To what extent is it a cautionary parameter? [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-15-06.

Peritumoral eosinophils predict recurrence in colorectal cancer

In colorectal cancer, the presence and extent of eosinophil granulocyte infiltration may render important prognostic information. However, it remains unclear whether an increasing number of eosinophils might simply be linked to the overall inflammatory cell reaction or represent a self-contained, antitumoral mechanism that needs to be documented and promoted therapeutically. Peri- and intratumoral eosinophil counts were retrospectively assessed in 381 primary colorectal cancers from randomly selected patients. Tumors were diagnosed in American Joint Committee on Cancer (AJCC)/Union Internationale Contre le Cancer (UICC) stage I in 21%, stage II in 32%, stage III in 33%, and stage IV in 14%. Presence and extent of eosinophils was related to various histopathological parameters as well as patients' outcome. Overall, peri- and intratumoral eosinophils were observed in 86 and 75% cancer specimens. The peritumoral eosinophil count correlated strongly with the intratumoral eosinophil count (R=0.69; P<0.001) and with the intensity of the overall inflammatory cell reaction (R=0.318; P<0.001). Both increasing peri- and intratumoral eosinophil counts were significantly associated with lower T and N classification, better tumor differentiation, absence of vascular invasion, as well as improved progression-free and cancer-specific survival. However, only peritumoral eosinophils, but not intratumoral, were an independent prognosticator of favorable progression-free (hazard ratio 0.75; 95% confidence interval 0.58–0.98; P=0.04) and cancer-specific survival (hazard ratio 0.7; 95% confidence interval 0.52–0.93; P=0.01)—independent of the intensity of overall inflammatory cell reaction. This was also found for patients with AJCC/UICC stage II disease, wherein the presence of peritumoral eosinophils was significantly associated with favorable outcome. In conclusion, the number of peritumoral eosinophils had a significant favorable impact on prognosis of colorectal cancer patients independent of the overall tumor-associated inflammatory response. Evaluation of peritumoral eosinophils represents a promising readily assessable tool and should therefore routinely be commented on in the pathology report.

Factores pronóstico en el carcinoma bronquial no microcítico menor de 3 centímetros (análisis actuarial, incidencia acumulativa y grupos de riesgo)

IntroductionIn TNM classification, factors determining the tumor (T) component in non-small cell lung cancer have scarcely changed over time and are still based solely on anatomical features. Our objective was to study the influence of these and other morphopathological factors on survival. MethodsA total of 263 patients undergoing lung resection due to stage I non-small cell lung cancer ≤3cm in diameter were studied. A survival analysis and competing-risk estimate study was made on the basis of clinical, surgical and pathological variables using actuarial analysis and accumulative incidence methods, respectively. A risk model was then generated from the results. ResultsSurvival at 5 and 10 years was 79.8 and 74.3%, respectively. The best prognostic factors were presence of symptoms, smoking habit and FEV1>60%, number of resected nodes>7, squamous histology, absence of vascular invasion, absence of visceral pleural invasion and presence of invasion more proximal than the lobar bronchus. All these were statistically significant according to the actuarial method. The factor “age<50 years” was close to the margin of statistical significance. Pleural invasion and vascular invasion were entered in the multivariate analysis. The competing-risk analysis showed a probability of death due to cancer of 14.3 and 35.1% at 5 and 10 years, respectively. Significant variables in the univariate and multivariate analyses were similar, with the exception of FEV1>60%. ConclusionsPleural invasion and vascular invasion determine survival or risk of death due to non-small cell lung cancer ≤3cm and can be used for generating a predictive risk model.

Actual 10-year survival following hepatectomy for hepatocellular carcinoma

ObjectivesThis study was conducted to compare 10-year survivors with patients who survived <10 years in a large Western series of patients submitted to hepatectomy for hepatocellular carcinoma (HCC). MethodsA retrospective review of a series of hepatic resections conducted in a referral centre for HCC between January 1987 and October 2002 was conducted. ResultsA total of 176 patients were analysed. Twenty-eight patients survived ≥10 years (Group A) and were compared with the 148 patients who did not (Group B). Group A had smaller tumours (5.7cm versus 8.2cm; P = 0.001) and a lower incidence of microvascular invasion (18.5% versus 37.1%; P = 0.004). Recurrence did not differ significantly (Group A 18/28, 64.3% versus Group B 94/148, 63.5%). Median time to recurrence was longer in Group A (70 months versus 15 months; P < 0.0001), and more patients in Group A were able to undergo curative treatment for recurrence (88.8% versus 40.4%; P < 0.0001). Multivariate analysis showed that lack of vascular invasion (P = 0.020), absence of perioperative transfusion (P = 0.014), and recurrence at >2 years after primary resection (P = 0.045) were significantly associated with 10-year survival. ConclusionsTen-year survival after liver resection for HCC can be expected in approximately 15% of patients. Recurrence does not preclude longterm survival. Recurrence at >2 years after resection, absence of vascular invasion, and absence of perioperative transfusion are independently associated with 10-year survival.

Elevated PIVKA-II is associated with early recurrence and poor prognosis in BCLC 0-A hepatocellular carcinomas.

To investigate the prognostic value of serum PIVKA-II (prothrombin induced by the absence of vitamin K or antagonist-II) in BCLC (Barcelona Clinic Liver Cancer) 0-A hepatocellular carcinoma (HCC) patients after curative resection. Preoperative sera were collected from 140 patients with BCLC 0-A HCCs undergoing curative resection during 2011-2012 in Zhongshan Hospital. Follow-up ended on November 2013. ELISA was used to detect the serum concentrations of preoperative PIVKA-II. The prognostic value of PIVKA-II and other clinicopathological factors was analyzed by the Kaplan-Meier method and the multivariate Cox proportional hazards model. During follow-up, 39 of 140 patients suffered recurrence and the 1-year recurrence rate was 27.9%. The high-PIVKA-II expression group had lower 1-year time to progression (TTP) compared with the low-expression group (54.8% vs 20.2%, p<0.001). Patients with high preoperative PIVKA-II expression showed a relatively higher risk of developing postoperative recurrence than those with low expression in the low-recurrence-risk subgroups, including α-fetoprotein ≤400ng/mL (45.4% vs 16.7%; p=0.006), tumor size ≤5 cm (54.2% vs 18.1%; p<0.001), single tumor (56.0% vs 19.1%; p<0.001), absence of satellite lesions (53.3% vs 19.8%; p=0.001), absence of vascular invasion (52.6% vs 14.9%; p=0.002), and Edmondson stage I/II (60.9% vs 20.3%; p<0.001). PIVKA-II was the strongest independent prognostic factor for TTP (hazard ratio, 2.877; 95% CI 1.524-5.429; p=0.001). Elevated PIVKA-II is associated with early recurrence of BCLC 0-A HCC after curative resection and can be considered a novel prognostic predictor.

Protein expression of the chemokine receptor CXCR4 and its ligand CXCL12 in primary cutaneous melanoma--biomarkers of potential utility?

Dysregulation of the CXCR4/CXCL12 axis, relevant in melanoma progression, activates cell cycle progression and migration via stimulation of the MAPK pathway. We sought to ascertain the cooperativity of the CXCR4/CXCL12 axis with established prognosticators and BRAF status in melanoma. Samples (n = 107) of primary cutaneous melanoma were assessed for protein expression of CXCR4 and CXCL12, and molecular analyses were performed to ascertain BRAF status. Univariate analyses of CXCR4 protein showed that the proportion of CXCR4 positives was greater in melanomas with absence of mitoses (P < .0001), absence of ulceration (P = .0008), and absence of regression (P = .02). Patients presenting at shallower stages (American Joint Committee on Cancer [AJCC] 1-2) exhibited a larger proportion of CXCR4 positives (76.9%, P < .0001 and 69.0%, P = .008), whereas those at deeper stages (AJCC 3-4) exhibited a larger proportion of negatives (75.0%, P = .004 and 66.7%, P = .22). In a multivariate analysis, lower odds of CXCR4 protein expression were associated with AJCC stage 3 (odds ratio [OR]=0.16, P = .01), AJCC stage 4 (OR=0.17, P = .04), and mitoses (OR=0.21, P = .01). Univariate analyses of CXCL12 protein showed that the proportion of CXCL12 negatives was significantly smaller in melanomas with depth of at least 1 mm, absence of ulceration, and absence of vascular invasion (P < .0001 for all). CXCR4 and CXCL12 appear to be biomarkers associated with established prognosticators of good and poor clinical outcome, respectively, in primary cutaneous melanoma. A BRAF mutation does not appear to be associated with CXCR4/CXCL12 axis upregulation in primary cutaneous melanoma.

Adiponectin Receptor Expression Predicts Favorable Prognosis in Cases of Hepatocellular Carcinoma

Obesity influences risk, progression and prognosis of various cancers including hepatocellular carcinoma (HCC). Adipose-tissue-derived adipokines has been considered to be involved in tumorigenesis and adiponecin, one such adipokine, has antiproliferative effect on obesity-related malignancies, though variable signal pathway mediated by adiponectin receptors-AdipoR1 and AdipoR2. In this study, we investigated expression of adiponectin and adiponectin receptors in tumor and non-tumorous hepatic tissues of HCC patients and its clinicopathological significance. We collected 75 HCC tissues and 70 non-tumorous hepatic tissues from HCC patients who underwent surgical resection. The tissue microarrays were constructed and immunohistochemical study for adiponectin, AdipoR1 and AipoR2 was performed. Adiponectin and AdipoR1 expression rates were significantly lower in HCC than non-neoplastic hepatic tissues (82.7 % vs. 97.1 % and 24.0 % vs. 90 %, P = 0.005 and <0.001, respectively). Immunopositivity for adiponectin was associated with small tumor size, low Edmonson-Steiner grade and absence of other organ invasion (P = 0.015, 0.021 and 0.028, respectively). AdipoR1 expression had association with absence of vascular invasion (P = 0.028) and AdipoR2 expression was correlated with lower histologic grade and low pathologic T-stage (P = 0.003 and 0.008, respectively). Cox regression analysis revealed that low expression of AdipoR1 and AdipoR2 were associated with increased risk of recurrence and death, respectively (hazard ration = 3.222 and 14.797, respectively). These findings suggest that loss of adiponectin, and adiponectin receptors expression is associated with aggressive clinicopathological features of HCC and AdipoR1 and AdipoR2 might serve as the independent prognostic factors for HCC patients.

Effects of sorafenib combined with chemoembolization and radiofrequency ablation for large, unresectable hepatocellular carcinomas

Background The prognosis of unresectable large hepatocellular carcinomas is poor. This study evaluated the efficacy and safety of sorafenib combined with transcatheter arterial chemoembolization and radiofrequency ablation in the treatment of hepatocellular carcinomas larger than 5 cm. Methods The treatment of 22 patients with large, unresectable hepatocellular carcinomas (5.0-16.5 cm) treated with sorafenib after transcatheter arterial chemoembolization combined with radiofrequency ablation between 2007 and 2011 was reviewed. The local effects, survival rates, toxicity, and prognostic factors were analyzed. Results During a follow-up of 9-49 months, 19 patients died and three survived. The median overall survival was 32 months. The overall cumulative 12, 24, and 36-month survival rates were 85.9%, 66.8%, and 23.5% respectively. Technical effectiveness was achieved in 12 out of 28 lesions (42.85%) at the first CT check. The median time to tumor progression was 21 months. The progression-free survival rates at 6, 12, and 24 months were 90.9%, 72.0%, and 38.4%, respectively. Combined therapy was generally well tolerated. There was only one major procedure-related complication, biloma (4.5%). Sorafenib-related adverse events exceeding grade 3 were hand-foot skin reaction (2/22, 9.1%), gastrointestinal hemorrhage (1/22, 4.5%), and diarrhea (2/22, 9.1%). The absence of vascular invasion before treatment was found to be the best prognostic factor in the univariate analysis. Conclusions Sorafenib combined with transcatheter arterial chemoembolization and radiofrequency ablation is a promising approach to the treatment of large, unresectable hepatocellular carcinomas. However, large-scale randomized clinical trials are needed to determine the future role of this treatment.

Margin-Infiltrating CD20+ B Cells Display an Atypical Memory Phenotype and Correlate with Favorable Prognosis in Hepatocellular Carcinoma

The role of infiltrating B cells in hepatocellular carcinoma has been overlooked for many years. This study is aimed to delineate the distribution, prognostic value, and functional status of B cells in human hepatocellular carcinoma. Immunohistochemistry was used to investigate the distribution and clinical significance of infiltrating CD20(+) B cells in a series of 120 patients with hepatocellular carcinoma. The results were further tested in an independent series of 200 patients with hepatocellular carcinoma. The functional status of CD20(+) B cells was determined by flow cytometry, immunofluorescence, and in vitro coculture assay. Infiltrating CD20(+) B cells were predominantly concentrated in the tumor invasive margin, compared with the peri- and intratumor areas. High density of margin-infiltrating B lymphocytes (MIL-B) positively correlated with small tumor size, absence of vascular invasion, and increased density of CD8(+) T cells (P < 0.05). Survival analyses revealed that increased number of MIL-Bs and their penetration through the tumor capsule were significantly associated with improved overall and recurrence-free survival, and were identified as independent prognosticators for patients with hepatocellular carcinoma (P < 0.05). Importantly, the results were further validated in another independent hepatocellular carcinoma cohort. Moreover, we found that MIL-Bs featured an atypical memory phenotype (IgD(-)IgG(+)CD27(-)CD38(-)), expressed surface markers characteristic of antigen-presenting cells, possessed tumor-killing potential by producing IFN-γ, interleukin 12p40 (IL-12p40), granzyme B, and TRAIL, and acted in cooperation with CD8(+) T cells. The profile of CD20(+) B cells in situ is a new predictor of prognosis for patients with hepatocellular carcinoma and provides a novel target for an optimal immunotherapy against this fatal malignancy.

Tumour‐associated macrophages might represent a favourable prognostic indicator in patients with papillary renal cell carcinoma

Tumour-associated macrophages (TAM) have been reported to be regulators of progression in various human cancers. We evaluated the prognostic relevance of TAM in a large series of patients with papillary renal cell carcinoma (PRCC). The impact of TAM on cancer-specific survival (CSS) in 177 patients with PRCC was assessed using the Kaplan-Meier method and log-rank test. A multivariate Cox regression analysis was performed with respect to CSS. The presence of TAM was noted in 112 of 177 (63%) tumours and was associated statistically significantly with favourable pathological parameters, including low pathological T stage, node-negative tumours, low tumour grade, absence of vascular invasion and papillary subtype (all P < 0.05), respectively. Five-year CSS probabilities for patients with TAM-positive tumours were 93.5%, compared with 72.5% in patients with TAM-negative tumours, respectively (P < 0.001). Multivariate analysis revealed node-positive tumours, distant metastases and UICC stage (I versus II-IV) as independent predictors of death from PRCC, whereas the presence of TAM was associated independently with favourable outcome (hazard ratio = 0.45, 95% confidence interval 0.24-0.84, P = 0.012). The presence of TAM was shown independently to reduce the risk of death from cancer by 55%. The presence of TAM should therefore become part of routine pathology reporting in PRCC.

Resminostat in advanced hepatocellular carcinoma (HCC): Overall survival subgroup analysis of prognostic factors in the SHELTER trial.

e15088 Background: Previously published results of the phase I/II SHELTER study demonstrated efficacy and safety of the novel pan-HDAC inhibitor resminostat in second-line treatment of HCC patients (pts) who had progressed under first-line sorafenib. As patient baseline characteristics might influence treatment outcome, an analysis of their potential influence on overall survival (OS) was performed. Methods: 45 pts with advanced-stage HCC and centrally confirmed radiologic progression under first-line sorafenib were included in a multi-center, two-arm trial. Resminostat was administered either alone or in combination with sorafenib. A Cox proportional-hazards model was used to evaluate the interaction between baseline characteristics and the effect of the two treatment groups on overall survival. Results: In the combination group, pts with Child-Pugh-A, ECOG 0 or absence of vascular invasion had a statistically significant lower risk of death compared to pts with Child-Pugh-B (HR 0.19, 95% CI 0.06-0.55), ECOG 1 (HR 0.15, 95% CI 0.05-0.44), or vascular invasion (HR 0.37, 95% CI 0.15-0.93), respectively. For pts with BCLC-B there was a strong trend, although not statistically significant, of a lower risk of death when compared to pts with BCLC-C (HR 0.43, 95% CI 0.13-1.49). Etiology, prior TACE therapy, extrahepatic spread and interval between first- and second-line treatment had no impact on overall survival in this study. Similar findings were observed in the monotherapy group. Comparing the impact of these baseline characteristics in the combination and monotherapy group, no statistically significant different influence on OS between both treatment groups was observed. Conclusions: Resminostat in combination with sorafenib provides a substantial OS benefit (median OS of 8.1 months) for advanced HCC patients who had developed progressive tumor disease under first-line sorafenib therapy. Subgroup analysis of patient baseline characteristics revealed a significant influence of Child-Pugh index, ECOG classification, and vascular invasion on overall survival, whereas e.g. the interval between first- and second-line treatment had no impact on overall survival. Clinical trial information: NCT00943449.

Krüppel-like factor expression and correlation with FAK, MMP-9 and E-cadherin expression in hepatocellular carcinoma

Whether a focal adhesion kinase (FAK)‑Krüppel‑like factor 8 (KLF8)‑matrix metalloproteinase (MMP)‑9/E‑cadherin signaling axis exists in hepatocellular carcinoma (HCC) remains unknown. In the present study, KLF8 expression and its clinicopathological significance in HCC was investigated to determine the correlation between KLF8 and FAK, MMP‑9 and E‑cadherin expression. Tissues were obtained from 60surgically resected HCC and normal tumor‑adjacent tissues. KLF8, FAK, MMP‑9 and E‑cadherin expression levels were examined by quantitative real‑time reverse transcription polymerase chain reaction (qRT‑PCR) and immunohistochemistry. In addition, KLF8, FAK, MMP‑9 and E‑cadherin protein expression levels were examined by western blot analysis in 5portal vein cancer emboli and corresponding HCC tissues. The clinicopathological data of the HCC patients were retrospectively analyzed. KLF8 mRNA expression was found to be significantly upregulated in HCC tumor tissues compared with normal tumor‑adjacent tissues(P<0.05). KLF8 protein was highly expressed in portal vein cancer emboli. KLF8 expression level was significantly higher in tumors with advanced TNM stages and vascular invasion compared with that in tumors with early TNM stage and absence of vascular invasion (P<0.05). KLF8 protein and mRNA expression in HCC positively correlated with that of FAK (r=0.362, P<0.001; and r=0.377, P<0.01, respectively) and MMP‑9 (r=0.392, P<0.01; and r=0.336, P<0.01, respectively), but negatively correlated with E‑cadherin (r=‑0.364, P<0.01; and r=‑0.410, P<0.01, respectively). Results of the current study highlight a novel FAK‑KLF8‑MMP‑9/E‑cadherin signaling axis during HCC progression.

Is there different correlation with prognostic factors between “non-mass” and “mass” type invasive ductal breast cancers?

PurposeTo investigate the association between non-mass type breast cancer and common clinical–pathological prognostic factors, compared with mass type breast cancer. Materials and methodsAfter institutional review board approval, retrospective blind review of contrast-enhanced breast MRI was carried out for 88 histologically proven breast invasive ductal carcinoma (IDC) patients, presenting from January 2008 to December 2011. Two radiologists assessed the images of each lesion for the morphologic enhancement type [mass enhancement or non-mass-like enhancement (NMLE)] and the distribution/internal enhancement of NMLE. Two pathologists evaluated the histological grade of IDC, presence or absence of ductal carcinoma in situ (DCIS), lymph node status, presence or absence of vascular invasion, and expression status of estrogen receptor (ER)/progesterone receptor (PR)/HER-2/p53 tumor suppressor gene (p53)/Ki-67. Inter-observer agreement was assessed with kappa test. Chi-square test and Spearman rank correlation were performed to explore the associations of morphologic enhancement type with the age, lesion size and the above pathological prognostic factors ResultsInter-observer agreement was excellent, with kappa>0.75. Morphologic enhancement type was significantly correlated with age (P=0.02), with NMLE more commonly seen in women less than 50 y/o. The size of NMLE was larger than that of mass and, with the increase of lesion size, proportion of NMLE among the cases increased (P=0.001). NMLE was also significantly correlated with low histologic grade of IDC (P=0.003) and presence of DCIS (P<0.001). There was no significant correlation between morphologic enhancement type and lymph node status, vascular invasion, ER/PR/HER-2/p53/Ki-67 status. The histological grade was higher in clumped enhancement than non-clumped (P=0.011). There was no correlation between enhancement distribution and prognostic factors ConclusionsNon-mass type breast cancer may not necessarily have worse prognosis than the mass type, due to lower histological grade and closely related to DCIS component, although it may has larger tumor size. Clumped enhancement may have worse prognosis than non-clumped enhancement.

Clinical impact of programmed cell death ligand 1 expression in colorectal cancer

BackgroundProgrammed cell death 1 (PD-1) receptor triggering by PD ligand 1 (PD-L1) inhibits T cell activation. PD-L1 expression was detected in different malignancies and associated with poor prognosis. Therapeutic antibodies inhibiting PD-1/PD-L1 interaction have been developed. Materials and methodsA tissue microarray (n=1491) including healthy colon mucosa and clinically annotated colorectal cancer (CRC) specimens was stained with two PD-L1 specific antibody preparations. Surgically excised CRC specimens were enzymatically digested and analysed for cluster of differentiation 8 (CD8) and PD-1 expression. ResultsStrong PD-L1 expression was observed in 37% of mismatch repair (MMR)-proficient and in 29% of MMR-deficient CRC. In MMR-proficient CRC strong PD-L1 expression correlated with infiltration by CD8+ lymphocytes (P=0.0001) which did not express PD-1. In univariate analysis, strong PD-L1 expression in MMR-proficient CRC was significantly associated with early T stage, absence of lymph node metastases, lower tumour grade, absence of vascular invasion and significantly improved survival in training (P=0.0001) and validation (P=0.03) sets. A similar trend (P=0.052) was also detectable in multivariate analysis including age, sex, T stage, N stage, tumour grade, vascular invasion, invasive margin and MMR status. Interestingly, programmed death receptor ligand 1 (PDL-1) and interferon (IFN)-γ gene expression, as detected by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) in fresh frozen CRC specimens (n=42) were found to be significantly associated (r=0.33, P=0.03). ConclusionPD-L1 expression is paradoxically associated with improved survival in MMR-proficient CRC.

Pathologic response to non-surgical locoregional therapies as potential selection criteria for liver transplantation for hepatocellular carcinoma

Preoperative locoregional treatments (PLT) are performed to avoid progression before liver transplantation for hepatocellular carcinoma (HCC). The objective of this study was to analyze the prognostic factors affecting the outcome in patients who received PLT. A retrospective analysis of patients who underwent liver transplantation (LT) was performed. All patients who underwent PLT with confirmed pathological diagnosis of HCC were included. The rate of tumor necrosis (TN) was assessed by microscopic histological examination. From January 1997 to December 2010, PLT was performed in 154 patients ROC analysis individuated a TN cut-off value at 40%. Ninety-one patients (59.1%) of the patients presented TN>40%. At multivariate analysis, TN<40% (HR=1.76; p=0.04) and vascular invasion (VI) (HR=2.16; p<0.01) were associated with lower Overall Survival (OS). At multivariate analysis, TN<40% (HR=1.59; p=0.001) and VI (HR=2.51; p=0.001) were significant associated with lower Disease Free Survival (DFS). One, 3 and 5 years OS was 87.9%, 82.0% and 69.1% for patients with TN>40% and 82.5%, 64.2% and 53.2% for those with TN<40% (p=0.02). Tumour size <5 cm (p=0.02); age <55 years (p=0.02); absence of VI (p=0.02) and multiple procedures (p=0.04) were predictive factors for TN>40%. Response to preoperative locoregional treatment can be used as potential selection criteria for LT.

Distinctive histopathological features of lepidic growth predominant node-negative adenocarcinomas 3–5 cm in size

IntroductionAdenocarcinoma of the lung is a morphologically heterogeneous group of tumors which includes a variable portion of different histologic subtype components: lepidic growth (LG), and acinar, papillary and solid subtypes. Among these, LG is a non-invasive component which is one of the major histological subtypes in small-sized adenocarcinoma (2cm or less). However, in large adenocarcinomas (3–5cm in size), the clinicopathological significance of LG components remains unclear. MethodsA series of 135 lung adenocarcinomas 3–5cm in size, without lymph node involvement, were reviewed and classified according to their percentage of LG components. We examined the correlation between the percentage of LG components and clinicopathological factors of these tumors. ResultsThere were 41 (30.4%) tumors with 50% or more LG (LG-predominant group). Female gender (p=0.039), smoking history of <20 pack-years (p=0.039), absence of pleural invasion (p=0.003), and absence of vascular invasion (p<0.001) were significantly more frequently observed in the LG-predominant group. LG-predominant tumors showed a significantly higher percentage of non-cancerous cell collapse area to tumor area compared with non-LG predominant tumors (p<0.001). The outcome of the LG-predominant type patients was significantly better than that of the non-LG predominant type patients in both recurrence-free survival (p<0.001) and overall survival (p<0.001). Multivariate analysis showed that LG-predominant tumor to be an independent favorable prognostic factor (HR=0.285, 95% confidence interval: 0.148–0.547, p=0.014). ConclusionNode-negative LG-predominant adenocarcinomas of 3–5cm in size showed less invasiveness compared to non-LG predominant tumors. And LG-predominant type patients had excellent surgical outcome.

Histological characteristics of small hepatocellular carcinomas showing atypical enhancement patterns on gadoxetic acid-enhanced MR imaging

To define the histological characteristics of hepatocellular carcinomas (HCCs) showing atypical dynamic enhancement patterns on gadoxetic acid-enhanced dynamic magnetic resonance imaging (EOB-MRI). We evaluated a total of 130 small (≤ 3 cm) HCCs from 114 patients that were surgically removed after EOB-MRI. Two radiologists blinded to the histological findings retrospectively classified the HCCs into typical or atypical lesions. Gross morphology, nuclear histological grade, presence of vascular invasion, and capsule formation and infiltration were compared between the two groups using Chi-square or Fisher tests. Atypical dynamic enhancement patterns were seen in 23 HCCs (17.7%). None of the atypical HCC showed vascular invasion (P < 0.001). Atypical HCCs also showed more frequently smaller size (1.6 ± 0.6 cm versus 2.1 ± 0.6 cm, P = 0.001) with 86.9% (n = 20) of which 2 cm or less in diameter (P = 0.001), vaguely nodular appearance (56.5% vs 3.7%, P < 0.001), and nuclear grade I (69.6% versus 6.5%, P < 0.001), while less frequently showed capsule formation (26.1% versus 77.6%, P < 0.001) or capsular infiltration (16.7% versus 77.1%, P = 0.005). Atypical HCCs on EOB-MRI may be characterized by the absence of vascular invasion, smaller (< 2 cm or less) size, vaguely nodular appearance, and well differentiation, and infrequent capsule formation or capsular infiltration.

Tumor size of hepatocellular carcinoma in noncirrhotic liver: A controversial predictive factor for outcome after resection

BackgroundHepatocellular carcinoma in noncirrhotic liver (NC-HCC) presents usually with large size, which is seen as a contraindication to liver transplantation (LT) or even resection. The objective of our single-center study was to identify prognostic factors following resection of large NC-HCCs and to subsequently devise a treatment strategy (including LT) in selected patients. MethodsFrom 2000 to 2010, 89 patients who had hepatic resection for NC-HCC (large ≥8 cm in 52) were analyzed with regard to pathological findings, postoperative and long-term outcome. ResultsFive patients died postoperatively. After a mean follow-up of 35 ± 30 months, NC-HCC recurred in 36 patients (26/47 survivors in group 8 cm+, 10/37 in group 8 cm−; p = 0.007). Five-year overall (OS) and disease-free survival (DFS) rates were significantly worse for group 8 cm+ (43.4% vs. 89.2% and 39.3% vs. 60.7% for group 8 cm−, p < 0.05). Seven patients underwent re-hepatectomy and/or LT for isolated intrahepatic recurrence, with 5-year DFS of 57.1%. In a multivariate analysis, the factors associated with poor OS and DFS were vascular invasion and tumor size ≥8 cm in the overall population and vascular invasion, fibrosis and satellite nodules in group 8 cm+. Adjuvant transarterial chemotherapy was a protective factor in group 8 cm+. In 22 isolated NC-HCC cases with no vascular invasion or fibrosis, tumor size had no impact on five-year DFS (85%). ConclusionsAlthough patients with NC-HCC ≥8 cm had a poorer prognosis, the absence of vascular invasion or fibrosis was associated with excellent survival, regardless of the tumor size. In recurrent patients, aggressive treatment (including LT) can be considered.