Targeting the stromal fibroblasts: a novel approach to melanoma therapy

Classically, cancer is thought of as a genetic disease, where the step-wise acquisition of mutations initiates and drives progression. More recent thinking posits that, although cancers are initiated through genetic mutation, progression is often the result of dynamic interactions between the tumor cells and their surrounding environment.     

Endoscopic ultrasound: impact on survival in patients with esophageal cancer

BACKGROUND: Esophageal carcinoma is an aggressive malignancy and long-term survival is poor. Endoscopic ultrasound (EUS) is an additional staging modality to assess locoregional extent of this disease. We hypothesized that EUS may improve survival through more effective staging and better optimization of treatment. METHODS: We performed a retrospective review of all patients presenting with esophageal cancer at our institution from 1993 to 2003 (n = 97) and compared outcomes between patients who underwent staging EUS and computed tomography (CT) versus CT alone. Survival was calculated using Kaplan-Meier methods and compared between groups using the log-rank test. Mean survival was compared using analysis of variance (ANOVA) methods. RESULTS: Overall 3-, 6-, and 12-month survival did not differ between the 2 groups (EUS: 92%, 84%, and 80% and CT: 83%, 67%, and 43%, log-rank P = .1), which held true despite stratification by treatment modality (all P >.1). The mean survival for the EUS group was 16 +/- 3 months and for the CT group, 12 +/- 1.5 months (P = .2). Further analysis by stage showed no difference in survival between the 2 groups (all P >.1). However, stage 2A and 3 surgical patients had better survival than nonsurgical patients (both P = .02) irrespective of staging modality. EUS patients were no more likely to receive surgical, neoadjuvant, or definitive chemoradiation than CT patients (all P >.1). CONCLUSIONS: Overall survival as well as survival by stage did not differ between patients who underwent staging via EUS and CT versus CT alone, and patients staged with EUS were not more likely to receive any one intervention. Irrespective of staging modality, stage 2A and 3 patients who underwent surgical intervention had better survival than those who did not receive an operation.     

Efficacy and Toxicity Profile of Methotrexate Chloroquine Combination in Treatment of Active Rheumatoid Arthritis

Background

The present study was conducted to study the efficacy and toxicity profile of methotrexate chloroquine combination in treatment of active rheumatoid arthritis.

Methods

24 patients of rheumatoid arthritis confirming to revised American Rheumatism Association (ARA) criteria were studied prospectively for twenty months. Clinical evaluation was made every 3 months. Clinical disease variables measured at each visit were number of joints with swelling, number of joints with tenderness and pain, duration of morning stiffness and physician and patient assessment of disease activity. Blood counts, liver function tests and other adverse effects due to drugs were monitored every 2 months.

Results

10 patients demonstrated more than 50% improvement. 4 patients withdrew from study, 2 because of excessive nausea and vomiting and 2 because of noncompliance. Other side effects noted were hyperpigmentation, photosensitivity, skin rashes, raised transaminases and stomatitis.

Conclusion

Methotrexate chloroquine combination has good efficacy and toxicity profile. Gastrointestinal side effects are most common and usually responsible for the discontinuation of the drugs.Key Words: Rheumatoid arthritis, Methotrexate, Chloroquine, Efficacy, Toxicity     

Use of leukocyte esterase-nitrate activity as predictive assays of significant bacteriuria.

The present study evaluated the usefulness of the 1-min leukocyte esterase-nitrite tests in a tertiary-care hospital as a screening procedure to detect significant bacteriuria and correlated the findings with culture results. A total of 531 urine samples were reviewed, of which 484 were evaluated. Of the evaluated samples, 113 positive cultures (23.4%) were found, of which 93 (82.3%) were detected by leukocyte esterase-nitrite tests. In addition, 365 of 371 (98.4%) urine samples with negative bacterial cultures were negative in leukocyte esterase and nitrite tests.     

Ethics roundtable debate: Child with severe brain damage and an underlying brain tumour

A young person presents with a highly malignant brain tumour with hemiparesis and limited prognosis after resection. She then suffers an iatrogenic cardiac and respiratory arrest that results in profound anoxic encephalopathy. A difference in opinion between the treatment team and the parent is based on a question of futile therapy. Opinions from five intensivists from around the world explore the differences in ethical and legal issues. A Physician-ethicist comments on the various approaches.     

Risk factors for postoperative mortality in bariatric surgery

Introduction. Appropriate patient selection is crucial to the success of bariatric surgery (BaS). The objective of this study was to identify risk factors of increased postoperative mortality in patients undergoing BaS on a national level. Methods. BaS patients ≥18 years old in the United States were identified from the 2001 Nationwide Inpatient Sample (NIS). The effect of gender, age, insurance status, and need for reoperation on postoperative mortality was examined using multivariate logistic regression accounting for the NIS stratified sampling design and using comorbidity adjustments appropriate for index hospitalization data. Results. Analysis of 7,452,727 discharges identified 10,503 bariatric surgical patients meeting inclusion criteria. Estimates were generalizable to a national cohort of 52,098 patients with age 41 ± 10 years (mean ± SE), 84% women, length of stay (LOS) 3.9 ± 0.2 days, and overall mortality of 4 per 1000 BaS patients. Risk factors for postoperative in-hospital mortality are shown (Table). Mean LOS of those who died was 17.6 ± 3.7 days. Conclusion. Based on national data, risk factors for increased postoperative mortality in BaS patients include male gender, age > 39 years, Medicaid insured, and need for reoperation. These data can assist in optimizing BaS patient selection.

∗.

	% of BaS population	Odds ratio for death∗	95% Confidence interval∗	P value∗
Female	84	(ref)	(ref)
Male	16	2.1	1.1-4.3	0.04
Age 18-39	46	(ref)	(ref)
Age 40-49	32	2.6	1.1-6.5	0.04
Age 50-59	19	4.3	1.7-11	0.002
Private Insurance	83	(ref)	(ref)
Medicaid	4.7	3.9	1.2-13	0.03
No reoperation†	99	(ref)	(ref)
Reoperation	1	22	5.4-88	0.0001

∗

Adjusted for factors in table plus race, region and comorbidities;

†

Reoperation during original admission; ref = referent group

Full-size table

     

Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction

BACKGROUND: Surgical resection of adenocarcinoma of the stomach is curative in less than 40 percent of cases. We investigated the effect of surgery plus postoperative (adjuvant) chemoradiotherapy on the survival of patients with resectable adenocarcinoma of the stomach or gastroesophageal junction. METHODS: A total of 556 patients with resected adenocarcinoma of the stomach or gastroesophageal junction were randomly assigned to surgery plus postoperative chemoradiotherapy or surgery alone. The adjuvant treatment consisted of 425 mg of fluorouracil per square meter of body-surface area per day, plus 20 mg of leucovorin per square meter per day, for five days, followed by 4500 cGy of radiation at 180 cGy per day, given five days per week for five weeks, with modified doses of fluorouracil and leucovorin on the first four and the last three days of radiotherapy. One month after the completion of radiotherapy, two five-day cycles of fluorouracil (425 mg per square meter per day) plus leucovorin (20 mg per square meter per day) were given one month apart. RESULTS: The median overall survival in the surgery-only group was 27 months, as compared with 36 months in the chemoradiotherapy group; the hazard ratio for death was 1.35 (95 percent confidence interval, 1.09 to 1.66; P=0.005). The hazard ratio for relapse was 1.52 (95 percent confidence interval, 1.23 to 1.86; P<0.001). Three patients (1 percent) died from toxic effects of the chemoradiotherapy; grade 3 toxic effects occurred in 41 percent of the patients in the chemoradiotherapy group, and grade 4 toxic effects occurred in 32 percent. CONCLUSIONS: Postoperative chemoradiotherapy should be considered for all patients at high risk for recurrence of adenocarcinoma of the stomach or gastroesophageal junction who have undergone curative resection.