Independent Determinants Of Overall Survival Research Articles

Epidemiology of the non-head and neck sebaceous carcinoma and implications for distant metastasis screening.

Extraocular sebaceous carcinoma (SC), particularly those outside the head and neck region, is rare and not well-described. This study aimed to explore the epidemiology and identify the prognostic factors of non-head and neck SC, describe the possible relevant factors of distant metastasis, and provide implications for distant metastasis screening. Data from the 17 registries in the Surveillance, Epidemiology, and End Results database were retrospectively collected for patients with SC outside the head and neck from 2000 through 2020. Overall survival (OS) and disease-specific survival (DSS) were the primary endpoints. Survival analysis was conducted through Kaplan-Meier curves, and multivariate analysis was carried out using Cox proportional hazard models. A total of 1,237 patients with SC outside the head and neck were identified. The mean age at diagnosis of the entire patient cohort was 67.7 years (30 to 90+ years), and the mean tumor size was 2.2 cm (0.1-16 cm). Patients with distant disease experienced the lowest OS (mean, 29.5 months) than those with localized disease and regional disease (p < 0.0001). Multivariate analysis revealed that age, tumor size, and stage were independent determinants of OS; age, stage, and primary site were independent determinants of DSS. Tumor grade and lymph node status had less prognostic value for survival. Undifferentiated tumors have a trend toward distant metastasis, especially those at the primary site of the trunk. The prognosis of the non-head and neck SC is excellent, while the survival of distant disease is very poor. Distant metastasis screening can be considered for undifferentiated tumors, especially those located in the trunk region with large tumor sizes.

Impact of the time of surgical delay on survival in patients with muscle-invasive bladder cancer.

Patients with muscle-invasive bladder cancer (MIBC) often experience a waiting period before radical surgery for numerous reasons; however, the COVID-19 outbreak has exacerbated this problem. Therefore, it is necessary to discuss the impact of the unavoidable time of surgical delay on the outcome of patients with MIBC. In all, 165 patients from high-volume centers with pT2-pT3 MIBC, who underwent radical surgery between January 2008 and November 2020, were retrospectively evaluated. Patients' demographic and pathological information was recorded. Based on the time of surgical delay endured, patients were divided into three groups: long waiting time (> 90 days), intermediate waiting time (30-90 days), and short waiting time (≤ 30 days). Finally, each group's pathological characteristics and survival rates were compared. The median time of surgical delay for all patients was 33 days (interquartile range, IQR: 16-67 days). Among the 165 patients, 32 (19.4%) were classified into the long waiting time group, 55 (33.3%) into the intermediate waiting time group, and 78 (47.3%) into the short waiting time group. The median follow-up period for all patients was 48 months (IQR: 23-84 months). The median times of surgical delay in the long, intermediate, and short waiting time groups were 188 days (IQR: 98-367 days), 39 days (IQR: 35-65 days), and 16 days (IQR: 12-22 days), respectively. The 5-year overall survival (OS) rate for all patients was 58.4%, and that in the long, intermediate, and short waiting time groups were 35.7%, 61.3%, and 64.1%, respectively (P = 0.035). The 5-year cancer-specific survival (CSS) rates in the long, intermediate, and short waiting time groups were 38.9%, 61.5%, and 65.0%, respectively (P = 0.042). The multivariate Cox regression analysis identified age, time of surgical delay, pT stage, and lymph node involvement as independent determinants of OS and CSS. In patients with pT2-pT3 MIBC, the time of surgical delay > 90 days can have a negative impact on survival.

Bclw Overexpression Predicts Aggressive Disease in B-Cell Lymphomas

B-cell lymphomas encompass a phenotypically and genetically heterogenous subgroup within hematologic malignancies. Despite this heterogeneity, the ability to evade apoptosis is a unifying feature across B-cell lymphomas, and alterations within the Bcl-2 family of apoptosis regulatory proteins is a key mechanism for this evasion. While overexpression of the anti-apoptotic Bcl-2 family member BCL2 has been widely described in multiple B-cell lymphomas, altered expression of other anti-apoptotic proteins within this family, including BCLX, MCL1, A1 and, in particular, BCLW has been under-investigated. This is highlighted by clinical trials of the BCL2 inhibitor, venetoclax, which found poor single agent activity in B-cell lymphomas that were thought to be highly BCL2-dependent. Therefore, we investigated the contributions of anti-apoptotic Bcl-2 proteins in B-cell lymphomas. Analysis of gene expression profiling datasets of patient samples of major B-cell lymphoma subtypes as compared to normal B-cells demonstrated differential overexpression of anti-apoptotic Bcl-2 proteins, with BCL2, BCLX and BCLW being significantly overexpressed in multiple B-cell lymphoma subtypes. Focusing on aggressive B-cell lymphoma subtypes, BCLW was consistently overexpressed across all major B-cell lymphoma subtypes. Notably, BCLW overexpression was maintained in high grade follicular lymphoma compared to low grade, whereas BCL2 levels decreased as grade increased. These findings indicate that BCLW overexpression is selected for in more aggressive B-cell lymphoma subtypes. BCLW overexpression in aggressive B-cell lymphoma cell lines conferred resistance to the non-specific BH3 mimetic navitoclax as well as to venetoclax. Further, analysis of diffuse large B-cell lymphoma (DLBCL) cell lines demonstrated that the combination of high BCLW/low BCL2 in GCB DLBCL and high BCLW/moderate BCL2 in non-GCB DLBCL is also associated with decreased navitoclax sensitivity, suggesting that high BCLW may confer treatment resistance. In accordance with this, analysis of patient outcomes in DLBCL demonstrates that patients exhibiting high BCLW levels with low BCL2 levels have poorer survival than those with low BCLW. Moreover, Cox regression analysis showed BCLW was an independent determinant of overall survival in DLBCL. Together, our results indicate that BCLW predicts for more aggressive disease in B-cell lymphomas and increased resistance to therapy. Disclosures Eischen: AbbVie Inc.:Research Funding.

Determinants and prognostic implication of improved left ventricular ejection fraction in chronic heart failure patients with reduced ejection fraction

Abstract Background Previous studies have demonstrated that left ventricular ejection fraction (LVEF) is not associated with overall survival in patients with chronic heart failure (CHF). This study aimed to examine if improved EF is associated with better survival in these patients. Methods Study subjects were selected from the database in the REDEAL trial, which included all patients with CHF and a LVEF of &amp;lt;50% referred to our hospital between 2009 and 2017. Of these, 902 patients completed at least twice echocardiography examinations (BL and FUP) at a minimal interval of 12 [median 17 (14–25)] months. Results At baseline, there were 522 patients with BL_EF &amp;gt;35% (aged 68±12 years, male 74.5%, median EF 44%) and 381 patients with BL_EF ≤35% (aged 65±13 years, male 74.5%, median EF 29%). Survival was similar between groups (76.6% vs. 73.8%, P=0.322). Over a median echocardiography follow-up of 17 months, FUP_ EF increased by 1.3% (−4.0–8.0%) in the subgroup of BL-EF&amp;gt;35% and increased by 11.0% (2.0–20.0%) in the subgroup of BL_EF≤35%. Survival analysis showed that absolute change in EF was significantly associated with survival in the subgroup of BL_EF≤35% but not in the subgroup of BL_EF&amp;gt;35%. Therefore, further analysis was conducted among patients in the subgroup of BL_EF≤35%. In this subset of BL_EF≤35%, improved EF was defined as a FUP_EF of &amp;gt;40%. 171 (44.9%) patients presented with improved EF, EF remained unchanged or reduced in the rest 210 patients (55.1%, FUP_EF≤40%). Patients with improved EF was associated with better survival over a median clinical follow-up of 19 (11–32) months (80.7% vs. 68.1%, P=0.001). Multivariable Cox regression analysis showed that improved EF remained an independent determinant of overall survival after adjusted for potential clinical covariates including age, sex, diabetes, hyperuricemia, renal dysfunction, coronary artery bypass grafting, sleep-disordered breathing, and prior ICD or CRT_D implantation (HR 0.59, 95% CI 0.38–0.91, P=0.018). In this subgroup of BL_EF≤35%, age and sex-independent determinants of improved EF included without prior myocardial infarction (OR 0.40, 95% CI 0.24–0.67, P&amp;lt;0.001), without ICD or CRT-D implantation (OR 0.32, 95% CI 0.17–0.61, P=0.001), and smaller LV end-diastolic diameter (OR=0.94, 95% CI 0.90–0.99, P=0.012). Conclusions Longitudinal improvement in LVEF is significantly associated with survival benefit in the subgroup of baseline EF≤35% but not in the subgroup of baseline EF&amp;gt;35%. In the subgroup of baseline EF≤35%, improved LVEF remains an independent determinant of survival benefit Determinants of improved LVEF in HF patients with baseline EF≤35% include without myocardial infarction, without ICD implantation, and smaller LV chamber at baseline. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This work was supported by the German Federal Ministry of Education and Research

Significant prognostic determinants in lung cancers of the superior sulcus: comparable analysis of resected and unresected cases

In this study, we aimed to identify prognostic determinants and to comparably analyze clinical features of patients with both resected and unresected superior sulcus tumors (SSTs). The data of 56 patients who underwent any treatment for an SST from 2004 through 2016 in our hospital were reviewed. Overall survival (OS) rates were estimated using the Kaplan-Meier method. Univariate and multivariate analyses were performed to determine independent prognostic factors for patients with resected and unresected SST separately. The number of patients with resected and unresected SSTs was 24 (43%) and 32 (57%), respectively. Of the 24 patients who underwent surgery, 20 received induction therapy, with 32% achieving pathological complete response. Complete resection (R0) was performed in 22 patients (92%). On multivariate survival analysis, preoperative serum carcinoembryonic antigen (CEA) level (median 8.3ng/ml, p = 0.021) was identified as the independent determinant of OS in surgical patients; whereas, initial treatment response (complete response or partial response, p = 0.032) was the independent OS indicator in non-surgical patients. The 5-year OS of the patient with resected and unresected SST was 68.8% and 29.1% (p = 0.008), respectively. Significant prognostic factors differ among patients stratified by the presence of surgical resection for SSTs. Preoperative CEA level in surgical candidates and initial treatment response in non-surgical patients were the independent factors associated with OS. Surgical candidates are expected to have more favorable survival than patients with unresectable SSTs.

Outcome after liver resection for primary and recurrent intrahepatic cholangiocarcinoma.

BackgroundLiver resection is the only curative therapeutic option for intrahepatic cholangiocarcinoma (ICC), but the approach to recurrent ICC is controversial. This study analysed the outcome of liver resection in patients with recurrent ICC.MethodsDemographic, radiological, clinical, operative, surgical pathological and follow‐up data for all patients with a final surgical pathological diagnosis of ICC treated in a tertiary referral centre between 2001 and 2015 were collected retrospectively and analysed.ResultsA total of 190 patients had liver resection for primary ICC. The 1‐, 3‐ and 5‐year overall survival (OS) rates were 74·8, 56·6 and 37·9 per cent respectively. Independent determinants of OS were age 65 years or above (hazard ratio (HR) 2·18, 95 per cent c.i. 1·18 to 4·0; P = 0·012), median tumour diameter 5 cm or greater (HR 2·87, 1·37 to 6·00; P = 0·005), preoperative biliary drainage (HR 2·65, 1·13 to 6·20; P = 0·025) and local R1–2 status (HR 1·90, 1·02 to 3·53; P = 0·043). Recurrence was documented in 87 patients (45·8 per cent). The mean(s.d.) survival time after recurrence was 16(17) months. Independent determinants of recurrence were median tumour diameter 5 cm or more (HR 1·71, 1·09 to 2·68; P = 0·020), high‐grade (G3–4) tumour (HR 1·63, 1·04 to 2·55; P = 0·034) and local R1 status (HR 1·70, 1·09 to 2·65; P = 0·020). Repeat resection with curative intent was performed in 25 patients for recurrent ICC, achieving a mean survival of 25 (95 per cent c.i. 16 to 34) months after the diagnosis of recurrence. Patients deemed to have unresectable disease after recurrence received chemotherapy or chemoradiotherapy alone, and had significantly poorer survival.ConclusionPatients with recurrent ICC may benefit from repeat surgical resection.

Comparison of Outcome of Hepatic Arterial Infusion Chemotherapy Combined with Radiotherapy and Sorafenib for Advanced Hepatocellular Carcinoma Patients with Major Portal Vein Tumor Thrombosis

Objective: To compare the outcome of hepatic arterial infusion chemotherapy combined with radiotherapy (HAIC + RT) versus sorafenib monotherapy in patients with advanced hepatocellular carcinoma (HCC) and major portal vein tumor thrombosis (PVTT). Methods: This retrospective study included 108 HCC patients with PVTT of the main trunk or first branch and Child-Pugh ≤7. Sixty-eight received HAIC + RT and 40 received sorafenib. Patients were then assigned to the HAIC + RT group (n = 36) and the sorafenib group (n = 36) through case-control matching. The decision to treat with HAIC + RT or sorafenib was left to the attending physician. Results: The median overall, progression-free, and postprogression survival were significantly longer in the HAIC + RT group than in the sorafenib group (9.9 vs. 5.3, p = 0.002; 3.9 vs. 2.1, p = 0.048; and 3.7 vs. 1.9 months, p = 0.02, respectively). Multivariate analysis identified HAIC + RT (hazard ratio = 2.02; 95% confidence interval, 1.14–3.57; p = 0.01) as a significant and independent determinant of overall survival. Conclusions: In patients with advanced HCC and major PVTT, survival was significantly longer in those treated with HAIC + RT than with sorafenib.

Esophageal squamous cell neoplasia is an independent negative prognostic factor for head and neck cancer patients.

Patients with head and neck cancer (HNC) have a high incidence of esophageal squamous cell neoplasms (ESCN). ESCN also has a negative impact on the survival of HNC patients. However, recent endoscopic advances enable the early detection of ESCN, and novel treatments may lead to improving survival rates for HNC patients with ESCN. HNC patients who underwent magnifying esophagogastroduodenoscopy (EGDS) from 2005 to 2012 were included in this study (n = 226). We analyzed the prevalence and prognostic value of ESCN in HNC patients and the difference in overall survival between HNC patients with and without ESCN. Thirty-four patients (15%) developed an ESCN during their clinical course. Of the 34 patients, 10 patients underwent endoscopic resection for ESCN and 10 patients underwent simultaneous chemoradiation therapy for HNC and ESCN. The 3-year survival rates in HNC patients with and without ESCN were 53% and 70%, respectively. Multivariate analysis identified the advanced clinical stage of the HNC [hazard ratio (HR) = 2.15; 95% confidence interval (CI) = 1.18-3.93; p = 0.012] and the presence of ESCN (HR = 1.73; 95% CI = 1.00-2.97; p = 0.049) as significant and independent determinants of overall survival. Our study suggests that although the survival of HNC patients with ESCN may be improved by routine EGDS during tumor surveys and by advances in endoscopy, the presence of ESCN still remains an independent negative prognostic factor for HNC patients.

Clinicopathological features and prognostic factors in angiosarcoma: A retrospective analysis of 200 patients from a single Chinese medical institute.

Angiosarcoma is a rare soft tissue sarcoma, and the data about its clinicopathological features and prognostic factors are limited. The purpose of the present study was to report a large series of angiosarcoma at a single institution. Clinical data from 200 cases of angiosarcoma from the Shanghai Cancer Center (Shanghai, China) between March 2006 and March 2014 were retrospectively analyzed. The study population included 97 males and 103 females with ages between 4 and 91 years (median, 53 years). According to the tumor location, 200 cases were divided into 4 groups: i) Tumors involving the head and neck; ii) breast; iii) viscera (including internal organs and bone); and iv) soft tissue (including trunk and extremities). Of the 113 patients with follow-up data, 46 patients succumbed to the disease with a median interval of 10 months. Tumor recurrence/metastasis was identified in 66 patients with a median interval of 4 months. The disease-free survival (DFS) rate at 5-years was 19.3% and the overall survival (OS) rate at 5-years was 40.8%. Site of tumor origin, size (≥5 cm) and histological differentiation influenced DFS (P=0.032, 0.038 and <0.001, respectively), and OS (P<0.001, 0.008 and <0.001, respectively) rates. Age (<65 years) and multimodal treatment correlated with improved OS (P=0.003 and <0.001, respectively). Tumor differentiation and treatment modality were identified to be independent determinants of OS (P<0.001 and 0.038, respectively). Tumor recurrence/metastasis was an independent predictor of DFS (P<0.001). The prognosis of angiosarcoma is poor and the mortality rate is high. The site of tumor origin, size, histological differentiation, age, treatment modality and tumor recurrence/metastasis are all significant prognostic factors. In the present study, multimodal treatment may improve the clinical outcome of patients with angiosarcoma.

Determining the epidemiologic, outcome, and prognostic factors of oral malignant melanoma by using the Surveillance, Epidemiology, and End Results database

BackgroundThe authors conducted a retrospective analysis to determine the epidemiologic, outcome, and prognostic factors in patients with oral malignant melanoma (OMM). MethodsThe authors used the US National Cancer Institute’s Surveillance, Epidemiology, and End Results database to analyze patients with OMM from 1973 to 2012. Study variables included age, sex, race, decade of diagnosis, extent of disease, tumor size, treatment modality, and socioeconomic status (SES). ResultsThe search identified 232 patients with OMM. Overall survival (OS) and disease-specific survival (DSS) were 25% and 40%, respectively, at 5 years. Age (OS, P = .004; DSS, P = .294), surgical resection (OS, P = .046; DSS, P = .005), and extent of disease (OS, P < .001; DSS, P < .001) were independent survival determinants; tumor size was an independent predictor of OS (P = .085). For confined and locally invasive disease, surgery (OS, P = .001; DSS, P = .004) and size (OS, P = .154; DSS, P = .007) were independent determinants of OS and DSS. For metastatic disease, surgery (OS, P = .675; DSS, P = .518) was a survival determinant for both OS and DSS, whereas radiotherapy predicted improved OS (hazard ratio, 0.18; 95% confidence interval, 0.03 to 0.99; P = .049). ConclusionsAge at diagnosis, decade of diagnosis, extent of disease, tumor size, and SES are prognostic factors related to OMM survival. Surgical resection and radiation therapy both improve OMM survival. Practical ImplicationsEarly and detailed examinations for OMM are critical to improving the survival rate in patients with OMM, especially in older patients and patients of lower SES.

Clinical outcome and prognostic factors in hepatocellular carcinoma patients with bone metastases medicated with zoledronic acid.

We retrospectively analyzed the clinical outcome and prognostic parameters in patients with hepatocellular carcinoma (HCC) and bone metastases who had received treatment with zoledronic acid (ZOL). Ninety-nine HCC patients with bone metastases who had been treated with ZOL were enrolled in this retrospective cohort study. We analyzed the prognostic factors, including serum N-telopeptide of type I collagen (NTX) levels, as bone metabolism markers. The median overall survival (OS) time was 11.5months. Child-Pugh grade A (P = 0.004) and intrahepatic tumor stage (IHTS) T0-3 (P = 0.010) correlated significantly with favorable OS. In 46 patients with grade A and T0-3, receiver operating characteristic curve analysis defined 16nmolBCE/L serum NTX as the cut-off level for median OS. Multivariate analysis identified baseline serum NTX <16nmolBCE/L (P = 0.045) as the only significant and independent determinant of OS. Low baseline serum NTX level correlated with favorable outcome in bone metastatic HCC patients with Child-Pugh grade A and IHTS T0-3 treated with ZOL.

Factors Associated With Survival in Patients With Synovial Cell Sarcoma of the Head and Neck: An Analysis of 167 Cases Using the SEER (Surveillance, Epidemiology, and End Results) Database.

Synovial cell sarcoma of the head and neck (SCSHN) is a rare tumor associated with significant morbidity and mortality. The literature regarding these tumors is limited to case series and case reports. We used data from the population-based US Surveillance, Epidemiology, and End Results (SEER) cancer registry to determine factors affecting both overall survival and disease-specific survival of patients with SCSHN. To determine the clinicopathologic and therapeutic factors determining survival in patients with SCSHN. The SEER registry was reviewed for patients with primary SCSHN from January 1, 1973, to January 1, 2011. Overall survival (OS) and disease-specific survival. A total of 167 cases of SCSHN were identified. The mean (SD) age at diagnosis was 37.9 (17.3) years, and 100 (59.9%) of the patients were males. The monophasic spindle cell and biphasic variants were the most common histologic subtypes. Surgical resection and radiotherapy were performed in 150 (89.8%) and 108 (64.7%) of the cases, respectively. The median OS at 2, 5, and 10 years was 77%, 66%, and 53%, respectively. Univariate Kaplan-Meier survival analysis revealed that age, race, and tumor stage and size were associated with improved survival. Histologic subtype was not associated with significant differences in survival. Radiotherapy was associated with improved disease-specific survival (hazard ratio [HR], 0.29 [95% CI, 0.12-0.68]; P = .003), but surgical management was not associated with improved survival (HR, 0.52 [95% CI, 0.19-1.46]; P = .21). Multivariate Cox regression analysis revealed that size greater than 5 cm (adjusted HR, 3.60 [95% CI, 1.43-9.08]; P = .007) and stage at presentation (adjusted HR, 3.86 [95% CI, 2.01-7.44]; P < .001) were independent determinants of OS. In separate analysis of cohorts with tumors 5 cm or less and larger than 5 cm, stage at presentation was found to be a significant indicator of the probability of survival in both cohorts (adjusted HR, 3.10 [95% CI, 1.46-6.60]; P = .003 and 5.32 [95% CI, 1.49-18.98]; P = .01, respectively); surgical resection and radiotherapy were not associated with differential survival outcomes using this model. Synovial cell sarcoma of the head and neck is rare. Independent significant determinants of survival include size (>5 cm) and stage at presentation. Histologic subtype of the tumor is not a significant indicator of the probability of survival. Surgical resection and radiotherapy were not independent determinants of survival.

Importance of cycles of chemotherapy and postdocetaxel novel therapies in metastatic castration-resistant prostate cancer.

PurposeWith the emergence of various novel therapies including new generation taxane and androgen-targeted therapies, the optimal sequence of systemic treatment in metastatic castration-resistant prostate cancer (mCRPC) patients remains to be defined. Our aim is to investigate the impact of duration of docetaxel-based chemotherapy and postdocetaxel treatment in mCRPC patients.MethodsThe medical data of 57 Chinese mCRPC patients who received docetaxel-based chemotherapy in two oncology centers between 2003 and 2012 were reviewed. The treatment efficacy and toxicity were determined. The potential determinants of efficacy were also determined.ResultsFifty-seven patients (median age 66 years, range 51–82 years) were given docetaxel-based chemotherapy, of whom 48 (84.2%) received 3-weekly docetaxel (52.5–75 mg/m2) and nine (15.8%) received weekly docetaxel (35 mg/m2). Postdocetaxel treatments were received by 31 (57.4%) patients, including abiraterone in 13 patients and cabazitaxel in one patient. The median follow-up time was 14.3 months. The median overall survival (OS) and progression-free survival were 20.8 months and 5.8 months, respectively. In multivariate analysis, eight cycles or more of chemotherapy [hazard ratio (HR) = 0.151, P < 0.0358], use of postdocetaxel treatment (HR = 0.346, P = 0.0005), and hemoglobin level of <10 (HR = 5.224, P < 0.0001) were independent determinants of OS. Patients who had received abiraterone and cabazitaxel as postdocetaxel treatment had significantly longer OS compared with those who received other postdocetaxel treatments (including rechallenge of docetaxel) and those who did not receive any postdocetaxel treatment (35.3 months vs. 20.8 months vs. 15.3 months, P = 0.00057).ConclusionsThe results suggest that maximizing exposure to docetaxel-based chemotherapy followed by novel therapies would have a favorable survival impact on mCRPC patients.

The Presence of Second Primary Esophageal Tumor (Spet) is Still an Independent Negative Prognostic Factor for Head and Neck Cancer (Hnc) Patients: a Retrospective Study

ABSTRACT Aim: Head and neck cancer (HNC) patients have a high incidence of primary esophageal tumor. Moreover, second primary esophageal tumor (SPET) also had a negative impact on survival of HNC patients and previous studies reported that 3-year survival rate of HNC patients with SPET was 0-15%. Therefore, the establishment of optimal management for HNC patients with SPET is crucial. Recent advances in endoscopy such as magnifying endoscopy enabling early detection of esophageal tumor and the novel treatment may lead to improve survival for HNC patients with SPET. Methods: A total of 226 HNC patients who underwent magnifying esophagogastroduodenoscopy at our institute from October 2005 to September 2012 were retrospectively examined in this study. We investigated the incidence of SPET, the difference in the therapeutic outcome between HNC patients with and without SPET and the prognostic value of the presence of SPET in HNC patients. Results: Out of 226 HNC patients, 34 patients (15%) had SPET during their clinical course. The median age was 71 years (range 51 to 88) and 33 patients were male. All patients had squamous cell esophageal carcinoma. The majority of patients (79%) had SPET with stage 0 (26%) or 1(53%) disease. Out of 34 patients with SPET, 10 patients (29%) underwent endoscopic resection for SPET and 10 patients (29%) underwent simultaneous chemoradiation therapy with cisplatin plus continuous infusional 5-fluorouracil for HNC and SPET. The median over survival was 23.9 months in HNC patients with SPET, as compared with 27.0 months in HNC patients without SPET. The 3-years survival rates in HNC patients with SPET and in HNC patients without SPET were 50.9% and 72.0 %, respectively. Multivariate analysis identified the clinical stage of HNC (p = 0.01, hazard ratio 2.36) and the presence of SPET (p = 0.03, hazard ratio 1.9) as significant and independent determinants of overall survival. Conclusions: Our study suggested that although survival of HNC patients with SPET might be considerably improved due to early detection and treatment of SPET, the presence of SPET still remained an independent negative prognostic factor for HNC patients. Disclosure: All authors have declared no conflicts of interest.

Clinical outcome of sorafenib treatment in patients with advanced hepatocellular carcinoma refractory to hepatic arterial infusion chemotherapy

It has been reported about poor prognosis in patients with advanced hepatocellular carcinoma (HCC) refractory to hepatic arterial infusion chemotherapy (HAIC). We assessed the survival benefits of sorafenib therapy for advanced HCC in HAIC refractory patients. The study subjects were 191 patients with advanced HCC who had been treated with HAIC. Sorafenib was used in 27 patients who finally failed to respond to HAIC (HAIC/sorafenib group). Clinical outcome was compared between HAIC/sorafenib and HAIC alone groups. There were no significant differences in clinical characteristics and response rate of HAIC between the two groups (response rate: 25.9%, HAIC/sorafenib group; 30.4%, HAIC alone group). The median survival time (MST) for all patients was 11.0 months. The survival rate was significantly higher in the HAIC/sorafenib group than HAIC alone group (MST 22.2 vs 8.7 months, P = 0.017). From administration sorafenib, the disease control rate was 51.8% with MST of 10.4 months. Among HAIC non-responders, the survival rate was significantly higher in the HAIC/sorafenib group than HAIC alone group. Multivariate analysis identified additional therapy with sorafenib as significant and independent determinant of overall survival in all patients and HAIC non-responders. Additional therapy with sorafenib could probably improve the prognosis of HAIC refractory patients.

Caspase-3 Expression in Human Gastric Carcinoma and Its Clinical Significance

Objectives: Caspase-3 is one of the most important molecules in the apoptosis cascade, and the relationship between caspase-3 expression and prognosis has been reported in many types of malignancies. However, the involvement of caspase-3 in human gastric carcinoma is not fully understood. We evaluated caspase-3 expression in human gastric carcinoma to clarify the clinicopathological importance and investigated the apoptosis avoidance mechanism by an immunohistological method. Methods: Specimens from 151 patients who underwent gastrectomy at the Department of Surgery and Surgical Basic Science of Kyoto University Hospital were investigated. Caspase-3 expression in cancer cells was evaluated by comparing its expression in the germinal center of the lymphoid follicle, and was quantified as the caspase-3 expression index (C3EI). C3EI was compared with the expression of Bcl-2 and the TdT-mediated dUTP biotin nick-end labeling (TUNEL) in 80 randomly selected cases. Actual activation of caspase-3 was determined by immunohistochemistry using monoclonal antibody that recognizes only activated caspase-3. Results: C3EI correlated significantly with lymph node metastasis (negative 105.5–78.7, positive 153.8 ± 66.1 p = 0.001) and the lower C3EI group had a better prognosis than the higher group (log-rank test, p = 0.0001). Cox multivariate analysis showed that age, operation curability, tumor invasion and C3EI were significant independent determinants of overall survival. Bcl-2 and TUNEL staining had no significant correlations with C3EI. Immunohistochemistry of activated caspase-3 revealed that most caspase-3 in gastric cancer cells was not activated, in accordance with TUNEL assay. Conclusions: Our results show that C3EI is a novel, independent prognostic factor in gastric cancer patients and cancer cells may avoid apoptosis by inhibiting caspase-3 activation.