Cumulative Overall Survival Rates Research Articles

Effect of nucleoside analog use in patients with hepatitis B virus‐related hepatocellular carcinoma

To examine the effect of nucleoside analog (NA) therapy on clinical outcome in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) who underwent curative therapy. A total of 131 patients with HBV-related HCC who underwent curative therapy were analyzed. They were divided into an NA group who received NA therapy (n = 99, group A) and a control group (n = 32, group B). Group A was further classified into two groups of patients who either received NA therapy before HCC therapy (n = 34, group Aa) or who received NA therapy with initial HCC therapy (n = 65, group Ab). Overall survival (OS) and recurrence-free survival (RFS) were compared in the three groups. The 1- and 3-year cumulative OS rates were both in group Aa, 100% and 88.0% in group Ab, and 100% and 75.7% in group B (overall significance, P = 0.002), respectively. The corresponding RFS rates were 93.1% and 36.0% in group Aa, 78.3% and 45.7% in group Ab, and 78.0% and 38.0% in group B (overall significance, P = 0.734), respectively. Multivariate analysis revealed that being part of group Aa (P < 0.001) or group Ab (P < 0.001) and having albumin levels of 4.0 g/dL or more (P = 0.040) were significantly associated with OS, while HCC stage (P = 0.001) and hepatitis B e-antigen positivity (P < 0.001) were independent predictors linked to RFS. NA therapy in patients with HBV-related HCC may improve survival after curative therapy.

Lack of correlation between the antibody to hepatitis B core antigen and survival after surgical resection for hepatitis C virus-related hepatocellular carcinoma

The impact of antibodies to hepatitis B core antigen (anti-HBc) on survival after curative surgical resection (SR) for hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) remains unclear. The aim of the present study was to examine the relationship between anti-HBc positivity and survival of HCV-related HCC patients who underwent curative SR. A total of 222 patients with HCV-related, hepatitis B surface antigen (HBsAg)-negative HCC who underwent curative SR were analyzed. They included 119 anti-HBc-positive patients (53.6%) and 103 anti-HBc-negative patients (46.4%). Overall survival (OS) and recurrence-free survival (RFS) rates were compared between the two groups. The median follow-up periods in the anti-HBc-positive and anti-HBc-negative groups were 3.4 years (range, 0.3-10.9 years) and 3.2 years (range, 0.5-10.9 years), respectively. The 1-, 3- and 5-year cumulative OS rates were 88.8, 70.2 and 50.0%, respectively, in the anti-HBc-positive group and 95.8, 77.1 and 61.7% in the anti-HBc-negative group (P=0.300). The corresponding RFS rates were 68.7, 33.0 and 20.0%, respectively, in the anti-HBc-positive group and 74.4, 38.5 and 16.5% in the anti-HBc-negative group (P=0.482). Multivariate analyses identified serum albumin ≥3.8 g/dl (P=0.005) and the presence of microvascular invasion (P<0.001) as independent factors linked to OS, and interferon therapy after surgery (P=0.011), α-fetoprotein ≥40 ng/ml (P=0.030) and the presence of microvascular invasion (P<0.001) were significant predictors linked to RFS. In subgroup analyses according to maximum tumor size and background liver disease in terms of OS and RFS, no significant difference between the anti-HBc-positive and anti-HBc-negative groups was observed except in patients with non-cirrhotic liver in terms of RFS. In conclusion, anti-HBc-positivity is not a useful predictor for survival of patients with HCV-related HCC after curative SR.

Comparison of clinical characteristics and survival after surgery in patients with non-B and non-C hepatocellular carcinoma and hepatitis virus-related hepatocellular carcinoma.

Background and aims: We compared clinicopathologic data and long-term clinical outcomes among patients with non-B and non-C hepatocellular carcinoma (NBNC-HCC) who underwent curative resection (group A, n=129), those with hepatitis B virus-related HCC (group B, n=62) and those with hepatitis C virus-related HCC (group C, n=284).Methods: Clinicopathologic characteristics and cumulative overall survival (OS) and recurrence-free survival (RFS) after curative resection were compared among the three groups.Results: The proportion of patients with non-liver cirrhosis (LC) or diabetes mellitus in group A was significantly higher than that in group B or group C. The mean maximum tumor size in group A was significantly larger than that of group B or group C. Cumulative 3-year OS rates after resection were 76% in group A, 79% in group B and 72% in group C (A vs. B, P=0.638; A vs. C, P=0.090; B vs. C, P=0.091; overall significance, P=0.088). The corresponding RFS rates after resection were 38% in group A, 36% in group B and 36% in group C (A vs. B, P=0.528; A vs. C, P=0.281; B vs. C, P=0.944; overall significance, P=0.557). In subgroup analyses in patients with LC, in those without LC and in those who satisfied the Milan criteria, similar results were obtained, i.e., the difference among the three groups did not reach significance in terms of OS and RFS.Conclusion: Long-term clinical outcomes in patients NBNC-HCC after curative resection were comparable to those in patients with hepatitis virus-related HCC after curative resection.

The Relation between Obesity and Survival after Surgical Resection of Hepatitis C Virus-Related Hepatocellular Carcinoma.

Background and Aims. We aimed to investigate the relationship between obesity and survival in hepatitis C virus-(HCV-) related hepatocellular carcinoma (HCC) patients who underwent curative surgical resection (SR). Methods. A total of 233 patients with HCV-related HCC who underwent curative SR were included. They included 60 patients (25.8%) with a body mass index (BMI) of > 25 kg/m2 (obesity group) and 173 patients with a BMI of < 25 kg/m2 (control group). Overall survival (OS) and recurrence-free survival (RFS) rates were compared. Results. The median follow-up periods were 3.6 years in the obesity group and 3.1 years in the control group. The 1-, 3-, and 5-year cumulative OS rates were 98.3%, 81.0%, and 63.9% in the obesity group and 90.0%, 70.5%, and 50.3% in the control group (P = 0.818). The corresponding RFS rates were 70.1%, 27.0%, and 12.0% in the obesity group and 70.1%, 39.0%, and 21.7% in the control group (P = 0.124). There were no significant differences between the obesity group and the control group in terms of blood loss during surgery (P = 0.899) and surgery-related serious adverse events (P = 0.813). Conclusions. Obesity itself did not affect survival in patients with HCV-related HCC after curative SR.

Radiofrequency ablation for hepatocellular carcinoma: the relationship between a new grading system for the ablative margin and clinical outcomes

In our previous study, we classified the radicality (R grading) of percutaneous radiofrequency ablation (RFA) therapy for single hepatocellular carcinoma (HCC) according to the extent of the ablated margin, and demonstrated that this grading system was useful for predicting local tumor progression (LTP) after RFA. The aim of this study was to measure the overall survival (OS), the recurrence free survival (RFS), and the distant recurrence (DR) rate for each R grade (A-D), and to examine the relationship between clinical outcome and R grading. This study involved 368 patients with solitary HCC who had undergone RFA. The mean tumor diameter was 2.0±0.7cm. We calculated the post-RFA cumulative OS, RFS, and DR rate for each R grade and analyzed the factors contributing to clinical outcomes. In the multivariate analysis, significant factors were as follows: tumor size >2cm, serum albumin >3.5g/dL, prothrombin time >70%, HCC recurrence within 1year, and R grading (grade A) in OS; cause of liver disease (hepatitis B), gamma glutamyl transpeptidase (GGT) >80IU/L, platelet count >10×10(4)/mm(3), and R grading (grade A or B) in RFS; GGT >80IU/L, platelet count >10×10(4)/mm(3), and R grading (grade A or B) in DR. In patients with sufficient Lipiodol accumulation (n=219), very similar results were obtained. However, in patients with grade A and B (n=232), R grade was not a significant independent factor linked to OS, although grade A patients had lower LTP rate. Our proposed R grading system appears to be useful for predicting clinical outcomes after RFA.

Outcomes for Patients (Pts) with Low-/Int-1-Risk Myelodysplastic Syndromes (MDS) with del5q Aged < 65 Years Treated with Lenalidomide (LEN) in MDS-003 and MDS-004: A Retrospective Combined Analysis

Abstract 1723 Background: Two multicenter studies (MDS-003/-004) found LEN leads to RBC transfusion independence (TI) in > 50% of pts with RBC transfusion dependent Low-/Int-1-risk MDS with del5q (List A et al. NEJM 2006;355: 1456–65; Fenaux P et al. Blood 2011;doi: 10.1182/blood-2011-01-330126). RBC-TI ≥ 8 wks with LEN was associated with significantly reduced risk of AML progression and death (Fenaux P et al. Blood 2011;doi: 10.1182/blood-2011-01-330126). Alternative therapy is required for pts failing LEN therapy. Aims: To assess predictive factors of LEN response and long term outcomes (especially after primary or secondary LEN failure) of pts Methods: LEN was administered as follows (all 28-d cycles): 5 mg/d on d 1–28 and 10 mg/d on d 1–21 or 1–28. RBC-TI ≥ 26 wks and cytogenetic response (CyR; IWG 2000) are reported. Overall survival (OS) and AML progression were assessed using Kaplan-Meier method. Response rates and outcomes in pts Results: The trials included 97 (33.9%) pts Conclusions: LEN-treated pts Disclosures: Fenaux: Celgene Corporation: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Johnson & Johnson: Honoraria; Merck: Honoraria; Cephalon: Honoraria; Novartis: Honoraria. Giagounidis: Celgene Corporation: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees. List: Celgene Corporation: Consultancy, Honoraria, Research Funding. Hellstrom-Lindberg: Celgene Corporation: Membership on an entity9s Board of Directors or advisory committees, Research Funding. Yu: Celgene Corporation: Employment, Equity Ownership. Skikne: Celgene Corporation: Employment. Shammo: Celgene Corporation: Honoraria, Research Funding, Speakers Bureau. del Canizo: Celgene Corporation: Spanish advisory committee.

Salvage surgery after failure of partial laryngectomy for laryngeal carcinoma

To study surgical managements, outcomes and the factors affecting prognosis of the primary recurrence following partial laryngectomy for laryngeal carcinoma. The clinical data of 77 patients with salvage surgery for primary recurrence following partial laryngectomy for laryngeal carcinoma were analyzed retrospectively. Fifty-one patients underwent salvage total laryngectomy and other 26 patients with salvage partial laryngectomy. Of them, 19 patients without previous radiotherapy received a combined therapy of surgery and radiotherapy. Survival rates were analyzed using Kaplan-Meier method. Prognosis factors were analyzed by Log-rank test and Cox regression. After salvage surgery, the 3-and 5-year cumulative overall survival rates were 59.1% and 52.7% respectively, and both the 3- and 5-year local recurrence rates were 30.7%. Most patients (48.4%) died of the failure at the primary sites. Multivariate analysis revealed the advanced T stage at initial presentation and the extra-laryngeal invasion of recurrent tumor were adverse prognostic factors for survival rate and also the advanced T stage at initial presentation influenced local recurrence rate. Salvage surgery for the primary recurrence following conservation treatment for laryngeal carcinoma can achieve promising results. Salvage total laryngectomy is the main therapeutic management in most recurrent patients. Salvage partial laryngectomy can achieve sound results in the patients selected carefully.

Adenoid cystic carcinoma of maxillary sinus: diagnosis, treatment and prognostic factors

To study the clinical characters, the outcomes of treatments and the factors affecting long-term treatment results of adenoid cystic carcinoma (ACC) of the maxillary sinus. The clinical data of 80 patients with ACC of the maxillary sinus treated initially were analyzed retrospectively. Survival rate, local recurrence and distant metastasis were analyzed using Kaplan-Meier method. Prognosis factors were analyzed by Log-rank test and Cox regression. The 5-, 10- and 15-year cumulative overall survival rates were 65.2%, 37.1%, 26.3% respectively and 5-, 10-, and 15-year disease-free survival rates 50.7%, 30.7% and 24.5% respectively. The 5-, 10- and 15-year cumulative local control rates were 68.5%, 47.3% and 47.3% respectively and the cumulative distant metastasis rate were 32.8%, 48.8% and 48.8% respectively. Prognostic factors affecting survival included T stage, pathologic grade and the modes of treatment (P < 0.05). Patients with combined therapy composed of surgery and radiation had a better local control, compared with surgery or radiation alone (χ(2) = 18.33, P < 0.01), and surgery combined with postoperative radiation was prior to preoperative radiation combined with surgery (χ(2) = 6.64, P < 0.05). Patients treated with surgery combined with preoperative radiation, either with doses of ≥ 60 Gy or with negative margins, had a better local control, compared with doses < 60 Gy and with positive margins (χ(2) = 5.06, P < 0.05). The most of patients (62.8%) died of local recurrence. The most of failure was due to recurrence. Combined therapy composed of surgery and radiation improves the local control and survival in patients with ACC of the maxillary sinus, compared with surgery or radiation alone. Surgery combined with postoperative radiation provides the best overall survival and local control and should be the first choice of treatments.

Co-evolution of cancer microenvironment reveals distinctive patterns of gastric cancer invasion: laboratory evidence and clinical significance

BackgroundCancer invasion results from constant interactions between cancer cells and their microenvironment. Major components of the cancer microenvironment are stromal cells, infiltrating inflammatory cells, collagens, matrix metalloproteinases (MMP) and newly formed blood vessels. This study was to determine the roles of MMP-9, MMP-2, type IV collagen, infiltrating macrophages and tumor microvessels in gastric cancer (GC) invasion and their clinico-pathological significance.MethodsParaffin-embedded tissue sections from 37 GC patients were studied by Streptavidin-Peroxidase (SP) immunohistochemical technique to determine the levels of MMP-2, MMP-9, type IV collagen, macrophages infiltration and microvessel density (MVD). Different invasion patterns were delineated and their correlation with major clinico-pathological information was explored.ResultsMMP2 expression was higher in malignant gland compared to normal gland, especially nearby the basement membrane (BM). High densities of macrophages at the interface of cancer nests and stroma were found where BM integrity was destroyed. MMP2 expression was significantly increased in cases with recurrence and distant metastasis (P = 0.047 and 0.048, respectively). Infiltrating macrophages were correlated with serosa invasion (P = 0.011) and TNM stage (P = 0.001). MVD was higher in type IV collagen negative group compared to type IV collagen positive group (P = 0.026). MVD was related to infiltrating macrophages density (P = 0.040). Patients with negative MMP9 expression had better overall survival (OS) compared to those with positive MMP9 expression (Median OS 44.0 vs 13.5 mo, P = 0.036). Median OS was significantly longer in type IV collagen positive group than negative group (Median OS 25.5 vs 10.0 mo, P = 0.044). The cumulative OS rate was higher in low macrophages density group than in high macrophages density group (median OS 40.5 vs 13.0 mo, P = 0.056). Median OS was significantly longer in low MVD group than high MVD group (median OS 39.0 vs 8.5 mo, P = 0.001). The difference of disease-free survival (DFS) between low MVD group and high MVD group was not statistically significant (P = 0.260). Four typical patterns of cancer invasion were identified based on histological study of the cancer tissue, including Washing pattern, Ameba-like pattern, Spindle pattern and Linear pattern.ConclusionsProteolytic enzymes MMP9, MMP2 and macrophages in stroma contribute to GC progression by facilitating the angiogenesis. Cancer invasion patterns may help predict GC metastasis.

Skp2 is an independent prognosticator of gallbladder carcinoma among p27Kip1-interacting cell cycle regulators: an immunohistochemical study of 62 cases by tissue microarray

AbstractDespite improvement in surgical techniques, prognosis of gallbladder carcinoma remains poor. It is desirable to identify prognostic biomarkers to aid in the development of targeted therapeutic strategies. Two SCFSkp2 ubiquitin ligase-related proteins, Skp2 and cyclin-dependent kinase subunit 1 (Cks1), are involved in post-transcriptional degradation of p27Kip1 tumor suppressor, which inhibits both cdk2/cyclin E and cdk2/cyclin A complexes and thus prevents transition to the S phase. However, the prognostic utility of p27Kip1-interacting cell cycle regulators has not been systematically assessed in gallbladder carcinoma. Immunohistochemistry was performed for p27Kip1, Skp2, Cks1, cyclin E, cyclin A, and Ki-67 in tissue microarrays of 62 gallbladder carcinomas with follow-up. The data were correlated with clinicopathological features and overall survival (OS). The cumulative OS rate for all 62 cases was 42.9% at 3 years. Aberrant labeling indices (LIs) of p27Kip1 (<20%), cyclin E (≥5%), cyclin A (≥5%), Cks1 (≥40%), and Skp2 (≥10%) were identified in 29, 58, 66, 21, and 57% of gallbladder carcinomas, respectively. By log-rank tests, downregulation of p27Kip1 (P=0.0319) and high LIs of Skp2 (P=0.0006), Cks1 (P=0.0460), cyclin E (P=0.0070), and Ki-67 (P=0.0037) were predictive of inferior OS. Furthermore, the combined expression status of Skp2 and Ki-67 robustly defined three prognostically different groups (P=0.0001). In multivariate comparison, Skp2 overexpression represented the strongest independent adverse prognosticator (P=0.004, risk ratio (RR): 5.538), followed by Ki-67 LI ≥50% (P=0.016, RR: 3.254) and American Joint Committee on Cancer stages II–IV (P=0.013, RR: 3.163). In conclusion, aberrations of p27Kip1-interacting cell cycle regulators are common in gallbladder carcinomas. Skp2 overexpression is highly representative of biological aggressiveness and independently associated with poor OS, suggesting that it is a promising novel target for therapeutic intervention in aggressive cases. The combined assessment of Skp2 and Ki-67 LIs effectively risk-stratifies gallbladder carcinomas with different prognosis, which is worth being prospectively validated in future study.

Conservative Surgical Treatment of Renal Cell Carcinoma: Clinical Experience and Reappraisal of Indications

During a 14-year period 36 patients who presented with renal cell carcinoma underwent conservative surgical treatment. The patients were divided into 3 groups according to treatment indications and condition of the contralateral kidney: group 1 included patients with a solitary kidney or bilateral tumors, group 2 patients had a damaged contralateral kidney and group 3 patients were without abnormalities of the contralateral kidney. Cumulative 6-year survival rates were 58 per cent for group 1, and 90 per cent for groups 2 and 3 combined. The over-all cumulative 6-year survival rate was 74 per cent. Based on these data extension of the indication for conservative surgical treatment seems to be justified in patients who present with low stage tumors and partial or potential damage to the contralateral organ. (J. Urol, 140: 725-731, 1988)