Toxic cardiogenic shock in a patient receiving weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin

A 54-year-old man was treated with weekly 24-h infusion of high-dose 5-fluorouracil (2600 mg/m2) and leucovorin (100 mg/m2) for metastatic colon cancer. At first, he tolerated the treatment well and no significant toxicity was identified. After a total of eight courses of treatment, a stable disease was observed, but mild shortness of breath was found on occasion. The patient had no previous history of cardiac disease and the heart performance assessed by left ventricular ejection fraction before treatment was normal. Unfortunately, acute pulmonary edema with lethal cardiogenic shock occurred during the ninth course of treatment, in spite of intensive medical treatment. The chest X-ray showed extreme cardiomegaly. Repeated assessment of his heart function by echocardiogram and ventricular ejection fraction revealed a very poor cardiac performance. Toxic cardiogenic shock during weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin is extremely rare. To the best of our knowledge, no case has been reported in the English literature. We report a case and the relevant literature about the incidence, clinical picture and possible pathophysiology on 5-fluorouracil-related cardioxicity is reviewed.      

Reduction of atherosclerosis in cholesterol-fed rabbits and decrease of expressions of intracellular adhesion molecule-1 and vascular endothelial growth factor in foam cells by a water-soluble fraction of Polygonum multiflorum

Polygonum multiflorum stilbeneglycoside （PMS） is a water-soluble fraction of Polygonum multiflorum Thunb. , one of the most famous tonic traditional Chinese medicines, that has protective effects on the cardiovascular system. The purpose of the present study is to elucidate the effects of PMS on macrophage-derived foam cell functions and the reduction of severity of atherosclerosis in hypercholesterolemic New Zealand White （NZW） rabbits. NZW rabbits were fed for 12 weeks with a normal diet, a high cholesterol diet, or a high cholesterol diet associated with irrigation with different doses of PMS （25, 50, or 100 mg/kg）. Treatment of NZW rabbits fed with high cholesterol diet with 100 mg/kg PMS attenuated the increase in plasma cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and plasma triglyceride. Treatment with 50 and 100 mg/kg PMS caused 43% and 60% decrease in atherosclerotic lesioned area ratio to total surface area, respectively. In U937 foam cells, PMS could decrease the high expression of intercellular adhesion molecule （ICAM）-1 protein and the vascular endothelial growth factor （VEGF） protein levels in the medium induced by oxidized lipoprotein when analyzed by flow cytometry. The results proved that PMS is a powerful agent against atherosclerosis and that PMS action could possibly be through the inhibition of the expression of ICAM-1 and VEGF in foam cells.     

Gastrointestinal haemorrhage due to erosion of the duodenal wall by a biliary stent

Complications from improperly placed biliary stents are not uncommon. Free loose wires from the ends of an uncovered stent can irritate and damage adjacent mucosal surfaces. Effective management can be achieved via percutaneous placement of a second stent to alter the orientation of the original stent.     

Relationship of vaginal pH and Papanicolaou smear results to vaginal flora and pregnancy outcome

Prematurity is a major cause of perinatal morbidity. Studies have implicated components of the vaginal flora in the etiology of some cases of preterm birth. Current scoring systems do not include factors which directly reflect the vaginal flora. Since Papanicolaou smears and the vaginal pH may be affected by the vaginal flora and are easy tests to perform, we studied their relationship to vaginal flora and pregnancy outcome. Among 231 patients, those with a vaginal pH greater than or equal to 4.4 were significantly more likely to carry Trichomonas vaginalis (P less than 0.03); Bacteroides species (P less than 0.01), and Mycoplasma hominis (P less than 0.001), and to have premature rupture of the membranes (P less than 0.01), and preterm rupture of the membranes (P less than 0.05). Patients with atypia reported on Papanicolaou smear more frequently carried M. hominis (P less than 0.01), and had premature rupture of the membranes (P less than 0.01). Although the high sensitivity and negative predictive value of those tests may make them useful additions to current scoring systems, their low specificity prevents them from being independent predictors of risk.     

Mammographic density and risk of breast cancer by age and tumor characteristics

Introduction

Understanding whether mammographic density (MD) is associated with all breast tumor subtypes and whether the strength of association varies by age is important for utilizing MD in risk models.

Methods

Data were pooled from six studies including 3414 women with breast cancer and 7199 without who underwent screening mammography. Percent MD was assessed from digitized film-screen mammograms using a computer-assisted threshold technique. We used polytomous logistic regression to calculate breast cancer odds according to tumor type, histopathological characteristics, and receptor (estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER2)) status by age (<55, 55–64, and ≥65 years).

Results

MD was positively associated with risk of invasive tumors across all ages, with a two-fold increased risk for high (>51%) versus average density (11-25%). Women ages <55 years with high MD had stronger increased risk of ductal carcinoma in situ (DCIS) compared to women ages 55–64 and ≥65 years (P_{age-interaction} = 0.02). Among all ages, MD had a stronger association with large (>2.1 cm) versus small tumors and positive versus negative lymph node status (P’s < 0.01). For women ages <55 years, there was a stronger association of MD with ER-negative breast cancer than ER-positive tumors compared to women ages 55–64 and ≥65 years (P_{age-interaction} = 0.04). MD was positively associated with both HER2-negative and HER2-positive tumors within each age group.

Conclusion

MD is strongly associated with all breast cancer subtypes, but particularly tumors of large size and positive lymph nodes across all ages, and ER-negative status among women ages <55 years, suggesting high MD may play an important role in tumor aggressiveness, especially in younger women.     

Additional mechanisms of hiatal hernia recurrence and its prevention

Summary The conventional hiatal hernia repair is a tension repair. Large defects such as those associated with an intrathoracic stomach can have a high rate of recurrence resulting in esophageal symptoms and in some instances gastric strangulation. Numerous additive procedures are used to secure the stomach in the abdominal cavity including mesh buttressing, fundoplication, anterior abdominal wall gastropexy and fundus diaphragmatic suture fixation. The optimal repair is unknown primarily because crura closure failure is poorly understood. A literature review was used to determine the proven causes of hiatal hernia recurrence. Early postoperative vomiting, surgeon inexperience, short esophagus and no crus closure are documented causes. In a series of 19 hiatal hernia recurrence repairs from our institution, additional causes such as suture pull-out and trauma have been established as additional mechanisms of recurrence. Increased intra-abdominal pressure associated with motor vehicle accidents was the precipitating factor in 2/19 patients. Suggested methods for prevention of hiatal disruption and resultant hernia are proposed which include: a postoperative antiemetic regimen, restricted activity in the early postoperative period, an assessment technique for the short esophagus when utilizing a laparoscopic approach, crus closure calibration and inclusion of the diaphragmatic fascia when performing hiatal closure for large paraesophageal hernias and the short esophagus.     

Public health reasoning: much more than deduction

The deductive paradigm has produced notable successes in epidemiology and public health. But while deductive logic has made a substantial contribution to the public health field, it must be recognized that there are also limits to that contribution. This report examines one such limit: the need for non-deductive models in public health reasoning. The findings of a study of public health reasoning in 879 members of the public are reported. Four non-deductive strategies were chosen for their capacity to bridge gaps in one’s knowledge. It emerged that subjects were adept at using these strategies in the absence of knowledge to arrive at judgements about public health problems. The implications of this finding for public health communication are discussed.     

Detection and viability of tumor cells in peripheral blood stem cell collections from breast cancer patients using immunocytochemical and clonogenic assay techniques [see comments]

Although peripheral blood stem cell collections (PBSC) are thought to have less tumor involvement than bone marrow (BM), the incidence of circulating tumor cells in patients with breast cancer has not been widely investigated. We prospectively investigated the incidence and viability of tumor cell involvement in PBSC and BM collections from breast cancer patients undergoing high-dose chemotherapy/hematopoietic stem cell transplantation. Paired samples of PBSC and BM from 48 patients were analyzed using an immunocytochemical technique that detects one epithelial-derived tumor cell per 5 x 10(5) mononuclear cells. Immunostained tumor cells were detected in 9.8% (13/133) PBSC specimens from 9/48 (18.7%) patients and in 62.3% (38/61) BM specimens from 32/48 (66.7%) patients, a significantly higher rate than in PBSC (P < .005). The geometric mean concentration of tumor cells in contaminated PBSC specimens was 0.8/10(5) mononuclear cells (range 0.33 to 2.0/10(5)) compared with 22.9/10(5) mononuclear cells in BM (range 1 to 3,000/10(5), P < .0001). In culture experiments, clonogenic tumor colonies grew in 21/26 immunocytochemically positive specimens. No tumor colony growth was detected in 30/32 immunocytochemically negative specimens. Immunocytochemical detection of tumor involvement in BM and PBSC correlated significantly with in vitro clonogenic growth (P < .0001). We conclude that PBSC contain fewer tumor cells than paired BM specimens from patients with advanced breast cancer and that these tumor cells appear to be capable of clonogenic growth in vitro.