Synchronous coexpression of epidermal growth factor receptor and cyclooxygenase-2 in carcinomas of the uterine cervix: a potential predictor of poor survival.

PURPOSE: To evaluate the potential of the new prognostic information gained by analyzing the coexpression of epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) in cervical cancer patients. EXPERIMENTAL DESIGN: Sixty-eight patients with International Federation of Gynecology and Obstetrics stage IIB squamous cell carcinoma of the uterine cervix, who underwent concurrent chemoradiotherapy between 1993 and 1996, were divided into the following four groups according to their immunoreactivities for EGFR and COX-2 in paraffin-embedded sections: (a). the EGFR-negative/COX-2-negative group (n = 11); (b). the EGFR-negative/COX-2-positive group (n = 8); (c). the EGFR-positive/COX-2-negative group (n = 27); and (d). the EGFR-positive/COX-2-positive group (n = 22). The clinical features, patterns of treatment failure, and survival data in the four groups were compared. RESULTS: Positive immunoreactivity for EGFR and COX-2 was observed in 49 of 68 (72%) and 19 of 68 (28%), respectively. However, no strong correlation was found between the levels of EGFR and COX-2 immunopositivity (R(2) = 0.05, P = 0.07). Patients in the EGFR-positive/COX-2-positive group had a higher likelihood of locoregional recurrence than those in the other three groups (P = 0.02). Of the patients in the four groups, patients positive for both oncoproteins were found to have the worst prognosis with an overall 5-year disease-free survival rate of 55% compared with 91% for the EGFR-negative/COX-2-negative patients, 88% for the EGFR-negative/COX-2-positive patients, and 69% for the EGFR-positive/COX-2-negative patients (P = 0.05, log-rank test). In addition, the synchronous coexpression of the EGFR and COX-2 oncoproteins was found to be an independent prognostic factor by univariate and multivariate analyses (relative risk = 4.0, P = 0.03). CONCLUSIONS: Given these observations, we conclude that the coexpression of EGFR and COX-2 immunoreactivity may be used as a potent molecular risk factor for predicting the poor survival of patients with the International Federation of Gynecology and Obstetrics stage IIB squamous cell carcinoma of the uterine cervix.     

Low expression of Bax predicts poor prognosis in patients with locally advanced esophageal cancer treated with definitive chemoradiotherapy.

PURPOSE: The present study evaluated the prognostic significance of apoptosis-related proteins, p53, Bcl-2, Bax, and galectin-3 in patients with locally advanced esophageal cancer treated with definitive chemoradiotherapy. EXPERIMENTAL DESIGN: A total of 63 patients with locally advanced esophageal cancer (squamous cell carcinoma: 62; adenocarcinoma: 1; stages II-IV) were treated with definitive chemoradiotherapy using 5-fluorouracil and cisplatin combined with radiotherapy. Pretreatment tumor biopsy specimens were analyzed for p53, Bcl-2, Bax, and galectin-3 expression by immunohistochemistry. RESULTS: High expression of Bax, p53, Bcl-2, and galectin-3 was observed in 67%, 47%, 24%, and 29% of patients, respectively. The median overall survival (OS) of total patients was 14 months with 16% of 3-year OS. High expression of p53, Bcl-2, and galectin-3 did not show correlation with clinicopathologic characteristics, including patient outcome. Low expression of Bax was significantly correlated with lack of clinical complete response (P=0.023). Low expression of Bax was also associated with poor OS (median, 8 months versus 16 months; P=0.0008) in univariate analysis. In multivariate analysis, low expression of Bax was the most significant independent predictor of poor OS (P=0.009), followed by low dose intensity of cisplatin and lack of clinical complete response. CONCLUSIONS: Low expression of Bax was significantly associated with the poor survival of patients with locally advanced esophageal cancer treated with chemoradiotherapy using 5-fluorouracil and cisplatin. Immunohistochemical staining for Bax with a pretreatment biopsy specimen might be useful to select the optimal treatment options for these patients.     

Contrasting predictors of poor antiretroviral therapy outcomes in two South African HIV programmes: a cohort study

Background  

Many national antiretroviral therapy (ART) programmes encourage providers to identify and address baseline factors associated with poor treatment outcomes, including modifiable adherence-related behaviours, before initiating ART. However, evidence on such predictors is scarce, and providers judgement may often be inaccurate. To help address this evidence gap, this observational cohort study examined baseline factors potentially predictive of poor treatment outcomes in two ART programmes in South Africa, with a particular focus on determinants of adherence.     

Is postoperative radiotherapy useful for the rectal carcinoma in the era of total mesorectal excision?

BACKGROUND/AIMS: The exact role of postoperative radiotherapy following curative surgery of rectal carcinoma has been debated. In this retrospective study, we examined the effect of radiotherapy on the survival and recurrence rate of rectal cancer patients who underwent total mesorectal excision. METHODOLOGY: Since June 1994, stage II and III rectal cancer patients have been recommended to receive postoperative chemoradiation. Among 175 consecutive patients who had undergone total mesorectal excision, 120 completed postoperative chemoradiation (group A) and 55 patients declined to receive radiation therapy (group B). For the two groups, survival and recurrence rates were compared. Mean follow-up time was 24.7 months. There was no difference between two groups with regard to sex, mean age, stage of the disease, mean tumor height, type of operation and mean follow-up duration. RESULTS: Overall recurrence rate showed no difference between the two groups (24.0% vs. 25.0%, P = 0.28). Local recurrence rate was also similar (10.0% vs. 6.0%, P = 0.11). There was no significant difference in duration to initial recurrence (14.0 months vs. 11.0 months, P = 0.18). The 5-year disease-free survival was 57% in group A and 63% in group B (P = 0.33). Disease-free survival in stage II was significantly better than in stage III. (78% vs. 42% overall, 70% vs. 37% in group A, 92% vs. 44% for group B, P < 0.01). CONCLUSIONS: In this study, we found no beneficial effect of postoperative radiation therapy following total mesorectal excision for the rectal cancer. So far, the prognosis was critically dependent on the stage rather than presence or absence of radiotherapy after total mesorectal excision.     

The attitudes of Korean cancer patients, family caregivers, oncologists, and members of the general public toward advance directives

Purpose

The purpose of this study was to investigate Korean attitudes toward advance directives (ADs) among cancer patients, family caregivers, oncologists, and the general public.

Methods

A multicenter survey study explored the attitudes of participants to ADs, and hospice–palliative care (HPC) was conducted. A total of 1,242 cancer patients, 1,289 family caregivers, 303 oncologists, and 1,006 members of the general public participated in the survey.

Results

The majority of patients, family caregivers, oncologists, and general public agreed with the necessity of ADs. However, oncologists regard “when became terminal status” as an optimal timing for completion of ADs (52.2 %), while other groups regard earlier periods as it. More than 95 % oncologist answered that cardiopulmonary resuscitation and mechanical ventilator are necessity items for ADs form, while around 70 % of other groups answered so. Multivariate analysis revealed that several factors including agreement with terminal disclosures and a positive attitude toward HPC were independently associated with necessity of ADs.

Conclusions

We found that attitudes toward ADs among cancer patients, family caregivers, oncologists, and the general public were significantly different. Our study also suggests that favorable attitudes toward comfort end-of-life care and HPC are keys that influence the perceived need for ADs.     

Reticuloendothelial Cell Function in a-Methyldopa-Induced Hemolytic Anemia

Abstract. 2 patients having α-methyldopa-induced hemolytic anemia were followed sequentially using an in vitro assay of autologous monocyte-macrophage activity to determine if their reticuloendothelial system (RES) function was abnormal and thus could be related to the mechanism of lysis. RES function was evaluated while the patients were actively hemolyzing and during remission, following discontinuance of the drug. The results indicated that RES activity is normal in patients having hemolytic anemia due to a-methyldopa administration. Also, following cessation of drug therapy, the patients' IgG-coated red cells interacted significantly for a prolonged period (4–5 months) with autologous or normal allogeneic monocyte-macrophages. This was associated with a concurrent reti-culocytosis and indicates a persistent low-level hemolytic phase throughout this period, even though hemoglobin and hematocrit values remained within the normal ranges. Although levels of IgG sensitizing the patients' red cells were essentially constant during the hemolytic phase and when the patients were in complete remission, significant monocyte-macrophage activity was only evident during the hemolytic period. In an attempt to explain this phenomenon, it is postulated that hemolysis in patients receiving α-methyldopa is related to the interaction of drug with red cell membrane proteins which results in a variably expressed 'altered' antigen which is recognized by 'autoantibody'. The proper expression of the Fc portion of the immunoglobin molecule to result in specific recognition by receptors on monocyte-macrophages depends upon the extent of the antigen alteration by α-methyldopa. If the drug does not result in appropriate antigen alteration, then, although 'autoantibody' may still bind to the red blood cell, its Fc region is not readily recognized by monocyte-macrophages and little or no erythrophagocytosis occurs.     

Physical activity status in relation to quality of life and dietary habits in breast cancer survivors: subset analyses of KROG 14-09 nationwide questionnaire study

Quality of Life Research - We investigated the relationship of physical activity with dietary habits and quality of life (QoL) in breast cancer survivors in accordance with the recommendations of...     

Rectal bleeding and its management after irradiation for uterine cervical cancer

PURPOSE: To present an evaluation of the risk factors of radiation-induced rectal bleeding and discuss its optimal management in patients with cancer of the cervix. METHODS AND MATERIALS: A total of 213 patients treated with radiotherapy (RT) alone were included. All patients underwent external beam radiotherapy with high-dose-rate brachytherapy. The rectal dose was calculated by both the International Commission on Radiation Units and Measurements (ICRU) Report 38 guidelines and the anterior rectal wall point on radiographs. Rectal bleeding was scored using the late effects normal tissue-subjective, objective, management, and analytic criteria. RESULTS: The incidence was 12.7% (27 of 213; Grade 1 in 9, Grade 2 in 16, and Grade 3 in 2). Most (92.6%) developed rectal bleeding within 2 years after RT completion (median 16 months). In univariate analysis, three significant factors were found: ICRU cumulative rectal biologically equivalent dose (CRBED) >100 Gy (19.7% vs. 4.2%), external beam RT dose to the parametrium >55 Gy (22.1% vs. 5.1%), and advanced stage (III-IV; 31.8% vs. 10.5%). In multivariate analysis, the ICRU-CRBED was the only significant factor. Six patients with Grade 1 bleeding experienced immediate relief with sucralfate enema for 1 month. For Grade 2 bleeding, sucralfate enema and/or coagulation were effective. Grade 3 bleeding lasted for 1 year despite frequent transfusions and coagulation. CONCLUSION: Grade 2 and 3 rectal bleeding occurred in 8.5% of patients. The most significant risk factor was the ICRU-CRBED. Prompt treatment with a combination of sucralfate enema and coagulation was effective in controlling Grade 1 and 2 rectal bleeding without the development of fistula or stricture.     

A validation study of new risk grouping criteria for postoperative treatment in stage IB cervical cancers without high-risk factors: Rethinking the Gynecologic Oncology Group criteria

Objective

The aim of this study was to verify whether the Gynecologic Oncology Group (GOG) criteria are valid in a different cohort of patients and to investigate simplified new criteria tailoring adjuvant radiation therapy in patients with intermediate-risk factors after radical hysterectomy.

Study design

We analyzed the data of 332 patients with FIGO stage IB cervical cancer who underwent radical hysterectomy between 1994 and 2007. Two hundred and twenty-five patients without high-risk factors (lymph node metastasis, parametrial invasion, or positive surgical margins) were identified and were classified into low-risk and high-risk groups according to the GOG criteria and new criteria based on combinations of intermediate-risk factors (large tumor size, deep stromal invasion, lymph-vascular space invasion). We evaluated the prognostic significance of both criteria.

Results

We identified 140 low-risk patients and 85 high-risk patients in the application of the GOG criteria. Low-risk patients had significantly better disease-free survival (DFS) (P = 0.001) and overall survival (OS) (P = 0.013) than high-risk patients. There were 145 low-risk patients and 80 high-risk patients on applying the new criteria. Low-risk patients had significantly better DFS (P = 0.001) and OS (P = 0.013) than high-risk patients. The receiver operating characteristic (ROC) curves showed that both criteria had similar performance for predicting which patients would have help from adjuvant therapy.

Conclusion

This study demonstrated that the GOG criteria were still valid in the different population, the simplified new criteria were convenient to apply in practice, and the performance of the new criteria was as good as the GOGs.