Department of Defense Era of Hope Meeting, Orlando, Florida, USA, 25–28 September 2002

Isoflavones possess both estrogenic and anti-estrogenic actions, and are hypothesized to protect against breast cancer. However, two intervention studies of markers of proliferation on breast tissue have raised concerns that soy isoflavones may have an estrogenic effect on breast tissue. Increased mammographic breast density is associated with an elevated risk of breast cancer, although the mechanism underlying this relationship has not been explained. Estrogens increase and anti-estrogens decrease breast density. Breast density may therefore serve as a biomarker of estrogenic or anti-estrogenic effects of a treatment on breast tissue. The effect of isoflavones on breast density is under investigation.     

Clinical observation of FMD regimen: Fludarabine,mitoxantrone, dexamethasone,in treatment of non-Hodgkin’s lymphoma

Objective

To evaluate the clinical effectivity and toxicity of the regimen FMD (fludarabine, mitoxantrone, dexamethasone) in patients with non-Hodgkin’s lymphoma.

Methods

Thirty-two patients, twenty-four of whom had indolent B-cell lymphoma, 6 peripheral T-cell lymphoma, two diffuse large B-cell lymphoma, received FMD. Treatment comprised: fludarabine 25～30 mg/m² days 1～3, mitoxantrone 8～10 mg/m² day 1, and dexamethasone 20～30 mg/m² days 1～5. At the same time, patients received prophylaxis against conditional infection with trimethoprim-sulfamethoxazole, fluconazole, acyclovir and immunoglobulin.

Results

Of the thirty-two patients treated, the complete response (CR) rate, partial response (PR) rate and overall response (OR) rate were 56.3%, 21.9% and 78.2% respectively. The CR and OR rate of 24 patients with indolent B-cell lymphoma were 66.7% and 88.3% respectively. Two of six patients with peripheral T-cell lymphoma were of complete response type and one was of partial response type. One of two patients with diffuse large B-cell lymphoma was partial response. The dominating toxicity was myelotoxicity and immunotoxicity. There was no treatment associated death in all patients treated with FMD. Grade 3～4 neutropenia occurred in 43.8% patients, 12.5% patients had infections and 9.3% developed grade 3～4 thrombocytopenia. At a median follow-up of 24 (5～54) months, the 2-year overall-survival rate and progression-free survival rate were (87.5 ± 1.4)% and (83.3 ± 1.6)% respectively. The 2-year OS and PFS rates of the indolent group were (93.75 ± 6.25)% and (87.5 ± 8.54)%.

Conclusion

FMD regimen was highly effective with low toxicity in the treatment of non-Hodgkin’s lymphoma, especially in indolent B-cell lymphoma. It also helps to improve the prognosis even in some aggressive lymphoma, such as peripheral T cell lymphoma.

     

Viagra, cialis, impase--which of them, to whom, when and how?

The study has been performed of the efficacy in the treatment of erectile dysfunction (ED) of oral drugs affecting nitric oxide: impase and phosphodiesterase-5 (PDE-5) inhibitors--sildenafil citrate (viagra), tadalafil (sialis)--alone and in combination with impase. A total of 218 ED patients aged 21-73 years (mean age 58.1 +/- 13.2 years) were divided into 3 groups comparable by the number of the patients, age, suspected etiology, pathogenesis and ED severity. Group 1 (n = 81) took viagra in the individually adjusted dose for 6 months; group 2 (n = 64) received sialis in a dose 20 mg for 6 months; group 3 (n = 73) took impase 1 tablet each other day sublingually for 6 months. Overall efficacy made up 77.8, 81.3 and 56.2% for viagra, sialis and impase, respectively. In view of different mechanism of action of PDE-5 inhibitors (viagra, sialis) and impase we combined the drugs in those who failed monotherapy or had drastic side effects. The combination raised efficacy of pharmacotherapy from 56.2 to 92.2%. We came to the conclusion that in psychogenic, isolated neurogenic, compensated and subcompensated arteriogenic ED of a mild or moderate degree, the treatment can be started with impase. If it was uneffective, in severe ED or moderate venoocclusive ED it is better to use PDE-5 inhibitors (viagra, sialis). If one of the latter fails, the other should be administered. If the inhibitors have low efficacy or in side effects, it is indicated to use their combination with impase.     

Changes of Serum Trace Elements,AFP, CEA,SF, T3, T4 and IGF-Ⅱ in Different Periods of Rat Liver Cancer

Objective: Based on liver cancer model built in SD rats, the contents of trace elements (Cu, Fe, Zn, Ca and Mg), AFP, CEA, SF, TH and IGF-II in serum were measured at different stages to explore the molecular changes during the rat liver cancer development. Methods: The SD rat liver cancer model was built by using diethylnitrosamine (DENA) as the mutagen. During 16 weeks of DENA gavage, blood samples were taken in the 14th, 28th, 56th, 77th, 105th and 112th days respectively after the first day of gavage wi...     

Dietary intake of vegetables, folate, and antioxidants and the risk of Barrett’s esophagus

Purpose

Diet is a potentially modifiable risk factor for Barrett’s esophagus (BE). We investigated the associations between intakes of fruits and vegetables and risk of BE.

Methods

We identified study subjects from 1,859 participants who underwent the endoscopy in a single VA Medical Center in the US between 2008 and 2011. Dietary intake in the previous year was elicited using a self-administered Block food frequency questionnaire (FFQ). Logistic regression model was used to estimate odds ratio (OR) and its 95 % confidence interval (CI) for BE.

Results

A total of 151 cases with definite BE and 777 controls completed the FFQ. When highest tertile of intake was compared with the lowest, the OR (95 % CI) was 0.46 (0.26–0.81) for dark green vegetables, 0.52 (0.30–0.90) for legumes, 0.50 (0.28–0.90) for total fiber, 0.45 (0.25–0.81) for isoflavones, 0.52 (0.30–0.67) for total folate, and 0.45 (0.26–0.79) for lutein, adjusting for multiple confounding factors including use of aspirin or proton pump inhibitor, gastro-esophageal reflux symptoms, and physical activity. The association for dark green vegetables was attenuated after adjustment for lutein, total fiber, and total folate (OR = 0.82; 95 % CI 0.30–2.22).

Conclusion

Higher intake of dark green vegetables was associated with a decreased risk of BE in a veteran population. Such an inverse association may be partially mediated by lutein, fiber, and folate. The novel findings on the association between intake of lutein, total folate, or isoflavones and risk of BE need further confirmation.     

Highlights of the American Society of Clinical Oncology Annual Meeting 2005 13–17 May, 2005, Florida,USA

In the past few years, major improvements and new technologies have been proposed and applied in esophageal surgery. Its evolution depended not only on a thorough knowledge of surgical anatomy and technique, but also on important developments in pre- and postoperative care. Esophageal resection for cancer is still associated with high morbidity and mortality. Postoperative complications may be either patient or surgeon related. Patient-related factors include age, malnutrition, immunodepression and associated diseases. The surgeon-related factors are surgical experience, hospital volume and multidisciplinary approach. Preoperative evaluation is defined as the process of clinical assessment that precedes the delivery of anesthesia. The principle is to gain information concerning patients that leads to modification of their management, and improves the outcome from surgery.     

Association of β-catenin,Wnt1, Smad4, Hoxa9, and Bmi-1 with the prognosis of esophageal squamous cell carcinoma

In our previous study, Human Signal Transduction in Cancer Gene Array was used in 12 fresh tumor samples to detect the gene expression profiles in the esophageal squamous cell carcinoma (ESCC) tissues matched adjacent non-cancerous samples. Among genes up-regulated at least twofold, β-catenin, Wnt1, Smad4, Hoxa9, and Bmi-1 were found. So subsequently, the aim of this study was to investigate the prognosis and clinicopathologic roles of β-catenin, Wnt1, Smad4, Hoxa9, and Bmi-1 in ESCC tissue. The mRNA and protein expression levels of β-catenin, Wnt1, Smad4, Hoxa9, and Bmi-1 genes in 70 ESCC and adjacent non-cancerous paraffin-embedded samples were determined by Real-Time Quantitative PCR (RT-PCR) and immunohistochemical staining. The mRNA expression level of β-catenin, Wnt1, Smad4, Hoxa9, and Bmi-1 in ESCC was significantly higher than that in the adjacent non-cancerous tissues (0.0821 ± 0.0416 vs. 0.0185 ± 0.0201, P = 0.0000; 1.9934 ± 1.9888 vs. 0.8863 ± 0.665, P = 0.0184; 0.0298 ± 0.0215 vs. 0.0189 ± 0.0187, P = 0.0017; 2.098 ± 0.091 vs. 1.016 ± 0.078, P = 0.0000; 2.181 ± 2.158 vs. 0.931 ± 0.894, P = 0.0152; respectively), and the protein expression level of determined genes was also significantly higher than that in the adjacent non-cancerous tissues (0.2835 ± 0.0844 vs. 0.2352 ± 0.0670, P = 0.0003; 0.3830 ± 0.0947 vs. 0.2721 ± 0.1474, P = 0.0000; 0.2637 ± 0.0348 vs. 0.2042 ± 0.0180, P = 0.0000; 0.2058 ± 0.0316 vs. 0.1218 ± 0.0518, P = 0.0000; 0.2736 ± 0.0834 vs. 0.2251 ± 0.0571, P = 0.0001; respectively). Then, the overexpression of mRNA and protein levels of β-catenin, Wnt1 and Bmi-1 was aggressively associated with lymph node metastasis, advanced pathological stage, and prognosis of the patients with ESCC (P < 0.05). The up-expression of Hoxa9 mRNA and protein was also aggressively associated with lymph node metastasis and advanced pathological stage (P < 0.05); however, the overexpression of Hoxa9 protein was not associated with the prognosis (P > 0.05). Meanwhile, the hypo-expression of Smad4 mRNA was aggressively associated with advanced pathological stage and prognosis of the patients with ESCC (P < 0.05); however, the hypo-expression of Smad4 protein was neutral to the prognosis and lymph node metastasis (P > 0.05). β-catenin, Wnt1, Smad4, Hoxa9, and Bmi-1 protein expression analysis showed that the positive outcomes of the combined detection of Wnt1 and β-catenin expression or Wnt1, β-catenin and Bmi-1 expression were significantly worse than those of a single target protein expression (P < 0.05). Meantime, the prognosis of the combined positive expression of Wnt1, β-catenin, and Bmi-1 was poorer than that in the combined positive expression of Wnt1 and β-catenin (P < 0.05). The prognosis of ESCC patients with the overexpression of Wnt1/β-catenin and Bmi-1 was relatively poor, and the level of Wnt1/β-catenin and Bmi-1 was conversely correlated with advanced pathological stage and lymph node metastasis. The expression level of Smad4 and Hoxa9 mRNA was also associated with the prognosis of the patients with ESCC, pathological stage, and lymph node metastasis; however, they might not be the independent prognostic factor.     

Antitumor effect of dehydroxymethylepoxyquinomicin, a small molecule inhibitor of nuclear factor-κB, on glioblastoma

Glioblastoma is the most malignant type of brain tumor. Despite recent advances in therapeutic modalities, the prognosis of glioblastoma remains very poor. Recent studies have indicated that RelA/nuclear factor (NF)-κB is consistently activated in human glioblastoma. In this study, we searched for a new treatment modality for glioblastoma, by examining the effects of dehydroxymethylepoxyquinomicin (DHMEQ), a unique small molecule inhibitor of NF-κB. Addition of DHMEQ to cultured human glioblastoma cells inhibited the nuclear translocation of RelA. It also reduced the growth rate of human glioblastoma cells significantly in 6 cell lines and modestly in 3 among 10 cell lines examined. Then, we performed further analyses using 3 sensitive cell lines (U87, U251, and YKG-1). The growth retardation was accompanied by G2/M arrest in vitro. Increased apoptosis was observed in U87 and YKG-1, but not U251 cells after DHMEQ treatment. Then, we tested the efficacy of DHMEQ in chemoprevention through the use of a nude mouse model. Subcutaneous tumors formed by U87 or U251 cells were reduced by ～40% in size by intraperitoneal administration of DHMEQ started immediately after implantation of the cells. DHMEQ treatment achieved statistically significant improvements in survival curves of mice intracranially implanted with U87 or U251 cells. Histological analysis revealed increased areas of necrosis, increased numbers of collapsed microvessels, decreased nuclear immunoreactivity of RelA, and decreased immunoreactivity of urokinase-type plasminogen activator in the DHMEQ-treated U87 tumor tissues. These results suggest that the targeting of NF-κB by DHMEQ may serve as a promising treatment modality in glioblastoma.     

Malignant mixed Müllerian tumors of the uterus: analysis of patterns of failure, prognostic factors, and treatment outcome

PURPOSE: To determine the survival outcomes, prognostic factors, and patterns of failure in patients with malignant mixed Müllerian tumor (MMMT) of the uterus. METHODS AND MATERIALS: Between 1954 and 1998, 300 patients with clinical Stage I-III MMMT of the uterus were treated with curative intent at The University of Texas M. D. Anderson Cancer Center. Their hospital records were reviewed to obtain patient and tumor characteristics; details of surgery, radiotherapy (RT), and chemotherapy; and long-term outcome. Surviving patients were followed for a median of 109 months (range 15-138). Survival rates were calculated using the Kaplan-Meier method, with differences assessed by log-rank tests. RESULTS: Of the 300 patients, 113 (38%) were treated with surgery alone, 160 (53%) with surgery plus adjuvant EBRT or ICRT, and 27 (9%) with RT alone. Forty-eight patients received adjuvant chemotherapy. At 5 years, the overall rates of survival and cause-specific survival were 31% and 33%, respectively. Women who were postmenopausal or had a history of prior pelvic RT, pain at presentation, clinical Stage II-III disease, uterine enlargement (>/=12 weeks), or an abnormal Papanicolaou smear finding had a significantly poorer prognosis than the other patients in the series. Of the 273 patients who underwent surgery, those who had positive abdominal washings, uterine length >10 cm, or extrauterine spread of disease to the cervix, adnexa, or peritoneum had a significantly worse prognosis than the other patients. Factors found on multivariate analysis to have an independent adverse influence on cause-specific survival included postmenopausal status (p = 0.0007, relative risk [RR] 3.3), uterine length >10 cm (p = 0.0001, RR 2.2), cervical involvement (p = 0.002, RR 1.8), and peritoneal involvement (p = 0.0001, RR 4.3). At 5 years, the rates of pelvic and distant disease recurrence for the entire group of 300 patients were 38% and 57%, respectively. The most common site of distant recurrence was the peritoneal cavity. Patients treated with pelvic RT had a lower rate of pelvic recurrence than patients treated with surgery alone (28% vs. 48%, p = 0.0002), but the overall survival rates (36% vs. 27%, p = 0.10) and distant metastasis rates (57% vs. 54%, p = 0.96) were not significantly different. However, patients treated with pelvic RT had a longer mean time to any distant relapse (17.3 vs. 7.0 months, p = 0.001) than patients treated with surgery alone. The use of adjuvant chemotherapy did not correlate with the survival rate or rate of distant metastasis. CONCLUSION: Adjuvant pelvic RT decreased the risk of pelvic recurrence and may delay the appearance of distant metastases after hysterectomy for MMMT. However, the survival rates remain poor because of a high rate of distant recurrence. As more effective systemic chemotherapy is developed to control microscopic distant disease, the role of RT in controlling locoregional disease in the pelvis and abdomen may become more important. Future research should consider programs that integrate surgery, RT, and chemotherapy to maximize the probability of cure.     

Prevalence,distress, management,and relief of pain during the last 3 months of cancer patients’ life. Results of an Italian mortality follow-back survey

BackgroundThis study estimates prevalence, management, and relief of pain during the last 3 months of life of a representative sample of dying cancer patients in Italy.Patients and methodsThis is a mortality followback survey (the Italian Survey of the Dying of Cancer). Caregivers were interviewed, after the patient’s death, about pain experienced by the patients in all settings of care.ResultsAccording to caregivers’ reports, 82.3% [95% confidence interval (CI) 79.9% to 84.4%] patients experienced pain, and 61.0% (95% CI 57.9% to 64.0%) very distressing pain. The younger population experienced a higher prevalence of pain in respect to older patients (P < 0.01). Patients with tumors of the central nervous system experienced the lowest prevalence (51.9%). According to caregivers’ reports, only 59.5% (95% CI 3.7% to 65.0%) received analgesic treatment with opioids for moderate to severe pain. Not surprisingly, pain was ‘only partially relieved’ or ‘not relieved at all’ in 54% of the patients with very distressing pain.ConclusionsAlthough potentially slightly biased, the results from this survey regarding undermedication and poor treatment results for cancer related pain are unequivocal. The research agenda should focus on testing the effectiveness of interventions to improve the quality of pain assessment and management.     

Influence of the Application of MRI on the T, N Staging System of Nasopharyngeal Carcinoma

OBJECTIVE To investigate the influence of utilizing MRI on the T, N staging system (the 5th edition, UICC) and on the 1992 China staging systems (Fuzhou-Guangzhou,China) by comparing the results of CT and MRI examinations of nasopharyngeal carcinoma (NPC).METHODS All 56 NPC patients, which were confirmed by histology,accepted both CT and MRI examinations. CT system scans were obtained by using an Elscient CT Twin Flash with the conventional axial scan. Three cases were examined by an additional coronary scan and 16 patients received an enhanced CT. The MR imaging was performed with a 0.5T MR system (Philips T5- II Ultra-Magnetic). The conventional axial, sagittal and coronary sections with SE sequences were obtained. The scan field was from the supra sellar cistern to the inferior border of C2. Most patients (50/56) accepted contrast enhanced MRI.RESULTS The pharyngobasilar fascia can clearly be seen on MRI but not on CT, so MRI can accurately determine the lesion in the nasopharyngeal cavity. MRI is more sensitive for evaluation of tumor involvement of soft tissue such as the Iongus colli muscle (14 cases by CT and 26 by MRI), tensor veli patalini muscle and levator veli palatini muscle (17 cases by CT and 23 by MRI), and skull-base bone marrow invasion (15 cases by CT and 42 by MRI). MRI can also demonstrate the invasion of the carotid sheath area and the enlargement of retropharyngeal lymph nodes more definitely than CT.The involvement of the trigeminal nerve can be detected on MRI, which may influence the clinical staging directly.CONCLUSION Of the 56 cases examined, 16 (28.6%) changed the staging based on UICC staging; while 33.9% (19/56) cases changed based on the 1992 China-stagin9 system. The major influence of MRI examinations on the 1992 staging was to differentiate the involvement of the carotid sheath area from metastasis of the retropharyngeal lymph nodes. There also was a significant difference in finding early invasion of the skull base.