Increased cumulative doses and appearance of hand-foot skin reaction prolonged progression free survival in sorafenib-treated advanced hepatocellular carcinoma patients.

Sorafenib has been recommended as a new palliative therapy for advanced hepatocellular carcinoma (HCC). However, the clinical outcome of patients receiving sorafenib therapy varies. This study sought to identify which clinical method could be used to predict clinical outcome of sorafenib monotherapy in patients with advanced HCC. A total of 146 advanced HCC patients with Child-Pugh A liver function were enrolled from June 2011 to September 2015. Sorafenib doses ranged from 200 mg once daily to 400 mg twice daily. Clinical and pathological parameters were collected. There was no predefined primary endpoint. Tumor response rate, adverse events, overall survival (OS), and progression-free survival (PFS) were analyzed. The follow-up period was 1718 days (median: 859 days). The median dosage of sorafenib was 562.35 mg.Forty patients (27.4%) had stable disease and 106 patients (72.6%) had progression disease. The OS was 432.21 ± 360.52 days (median: 329 days) and PFS was 167.05 ± 166.50 days (median: 102.5 days). No sorafenib toxic effect-related mortality was encountered. The most common severe adverse events (≧grade 3) were hand-foot skin reactions (HFSR) (16, 11.0%), diarrhea (7, 4.8%), and alopecia (1, 0.7%). The following patients had longer median PFS (mPFS): those receiving total dosage > 55000 mg (217 vs.63 days; HR = 0.20,95%CI = 0.11-0.38; p < 0.001), those receiving daily dosage <562 mg (140 vs.69 days; HR = 0.27, 95%CI = 0.17-0.46; p < 0.001), those with treatment durations > 112 days (231vs.64 days; HR = 0.37, 95%CI = 0.19-0.74; p < 0.001), and those with HFSR (105 vs.75 days; HR = 0.60,95% CI = 0.6-0.98; p = 0.04). In conclusion, increased cumulative doses of sorafenib as well as the appearance of HFSR were indicators of prolonged mPFS in sorafenib-treated advanced HCC patients.

Trousseau's syndrome in a patient with advanced stage gastric cancer.

Patients with cancer are at high risk for thrombotic events, which are known collectively as Trousseau's syndrome. Herein, we report a 66-year-old male patient who was diagnosed with terminal stage gastric cancer and liver metastasis and who had an initial clinical presentation of upper gastrointestinal bleeding. Acute ischemia of the left lower leg that resulted in gangrenous changes occurred during admission. Subsequent angiography of the left lower limb was then performed. This procedure revealed arterial thrombosis of the left common iliac artery with extension to the external iliac artery, the left common iliac artery, the posterior tibial artery, and the peroneal artery, which were occluded by thrombi. Aspiration of the thrombi demonstrated that these were not tumor thrombi. The interesting aspect of our case was that the disease it presented as arterial thrombotic events, which may correlate with gastric adenocarcinoma. In summary, we suggested that the unexplained thrombotic events might be one of the initial presentations of occult malignancy and that thromboprophylaxis should always be considered.

An evaluation of fatty acid-CoA ligase 4 in breast cancer.

BACKGROUND: Fatty acid-CoA ligase 4 (FACL4) has been detected in various types of tumors. However, there is still very limited information about the role of FACL4 in breast cancer. Tissue microarray (TMA) technique analyzes thousands of specimens in a parallel fashion with minimal damage to the original blocks. This study was designed with the application of TMA to analyze the FACL4 status in breast cancer. MATERIALS AND METHODS: Archival tissue specimens from 102 patients with primary invasive breast cancer were selected and FACL4 expression was analyzed by immunhistochemical staining with TMA. The data of primary tumor staging, age, estrogen receptor status, lymph node status, histological grading and TNM staging were also collected. RESULTS: As shown my multivariate analysis, TNM stage was significantly related to the overall five-year survival rate. Nevertheless, FACL4 expression failed to have any significant relationship to overall five-year survival. CONCLUSION: Immuno-histochemical staining with TMA was convenient and feasible for the analysis of FACL4 expression status in breast cancer. Our preliminary results showed that FACL4 expression had no significant prognostic value in breast cancer.

An evaluation of focal adhesion kinase in breast cancer by tissue microarrays.

BACKGROUND: Many studies have shown that focal adhesion kinase (FAK) is a positive regulator of tumor progression and invasion. However, there is still very limited information about the role of FAK in breast cancer. Tissue microarrays (TMA) can analyze thousands of tissue samples in a parallel fashion with minimal damage to the origin block. This study was designed with the application of TMA to analyze the FAK status in breast cancer. PATIENTS AND METHODS: Archival tissue specimens from 98 patients with primary invasive breast cancer were selected and FAK expression was analyzed by immunohistochemical staining with TMA. The data of primary tumor staging, age, estrogen receptor status, lymph node status, histological grading and TNM staging were also collected. RESULTS: There were four patients (4.0%) with grade 1 expression in FAK, 41 patients (41.8%) with grade 2 expression in FAK and 53 patients (54.2%) with grade 3 expression in FAK. There was no significant relationship between FAK expression and age, estrogen receptor status, histological grading, primary tumor staging, lymph node status and TNM stage. By multivariate analysis, the TNM stage was found to be significantly related to the overall five-year survival rate (p<0.00001). CONCLUSION: Immunohistochemical staining with TMA is a convenient and feasible method. Unfortunately, our preliminary results fail to show meaningful prognostic value of FAK in breast cancer. A larger prospective study is warranted for further evaluation.

Impact of combined hospice care on terminal cancer patients.

BACKGROUND: Many patients with advanced cancer will develop physical and psychological symptoms related to their disease. These symptoms are infrequently treated by conventional care. Palliative care programs have been developed to fill this gap in care. However, there are limited beds in hospice units. To allow more terminal cancer patients to receive care from a hospice team, a combined hospice care system was recently developed in Taiwan. This study is a report of our experiences with this system. PATIENTS AND METHODS: From January to December 2009, terminal cancer patients who accepted consultation from a hospice team for combined hospice care were enrolled in the study. Demographic data, clinical symptoms, referring department, type of cancer, and outcome were analyzed. RESULTS: A total of 354 terminal cancer patients in acute wards were referred to a hospice consulting team. The mean patient age was 61 years, and the proportion of males was 63.28%. After combined hospice care, there was a significant improvement in the sign rate of do-not-resuscitate (DNR) orders from 41.53% to 71.47% (p < 0.0001), and awareness of disease prognosis from 46.05% to 57.69% (p = 0.0006). Combined hospice care also enabled 64.21% of terminal cancer patients who were not transferred to hospice ward to receive combined care by a hospice consulting team while in acute wards, thus increasing the hospice utilization of terminal cancer patients. The major symptoms presented by the patients were pain (58%), dyspnea (52%), constipation (45%), and fatigue (23%). CONCLUSIONS: Through the hospice consulting system, hospice combined care has a positive effect on the utilization of hospice care, rate of DNR signing and quality of end-of-life care for terminal cancer patients.

Differences between inpatient hospice care and in-hospital nonhospice care for cancer patients.

BACKGROUND: Decisions for the type of palliative care are affected by multiple factors. Currently, most patients die without palliative care, and hospice patients receive only a brief period of services before death. OBJECTIVE: This study aimed to compare palliative terminal cancer care in inpatient hospice and nonhospice care units in Taiwan for type of cancer, cost, stay, and selected demographic and clinical characteristics. METHODS: A retrospective study of terminally ill cancer patients hospitalized in a hospice unit (410 patients) or a general cancer ward (3005 patients) in a hospital in Taiwan was conducted. Patient demographic information, length of stay, cost of treatments, interventions and diagnostic testing, and types of cancer were analyzed. The factors associated with hospice care were revealed by multivariate stepwise regression. RESULTS: In the hospice group, the total cost was lower; there were more female, and more head, neck, and lung tumor patients. The most tumors in nonhospice group are hepatomas. The patients in hospice group received fewer interventions and had a long hospital stay (>14 days) before death; however, most of them were discharged from the hospital due to death. CONCLUSIONS: Utilization of hospice care varies by sex and type of cancer. Compared with the nonhospice service, hospice care needs a lower total cost and fewer interventions. IMPLICATIONS FOR PRACTICE: Hospice care in Taiwan should provide more services and facilities specific for sex (female) and tumors (head and neck).

Cancer-specific activation of the survivin promoter and its potential use in gene therapy.

Survivin is expressed in many cancers but not in normal adult tissues and is transcriptionally regulated. To test the feasibility of using the survivin promoter to induce cancer-specific transgene expression in lung cancer gene therapy, a vector expressing a luciferase gene driven by the survivin promoter was constructed and evaluated in vitro and in vivo. We found that the survivin promoter was generally more highly activated in cancer cell lines than in normal and immortalized normal cell lines. When delivered intravenously by DNA:liposome complexes, the survivin promoter was more than 200 times more cancer specific than the cytomegalovirus promoter in vivo. To identify lung cancer patients who may benefit from gene therapy with the survivin promoter, we measured survivin protein expression in surgical specimens of 75 non-small-cell lung cancers and 10 normal lung tissues by immunohistochemical staining and found that survivin is expressed in most of the non-small-cell lung cancers tested (81%, 61 of 75) but none of the normal lung tissues. The survivin promoter also induced transgene expression of a mutant Bik in cancer cells, which suppressed the growth of cancer cells in vitro and in vivo. These results indicate that the survivin promoter is a cancer-specific promoter for various cancers and that it may be useful in cancer gene therapy.