Further experience with radiation therapy and concomitant intravenous chemotherapy in advanced carcinoma of the lower female genital tract

Sixty-seven patients with advanced carcinoma of the lower female genital tract (cervix, vagina, and vulva) were treated with radiation and concomitant intravenous cisplatin and/or 5-fluorouracil. Fifty-seven patients (85%) responded completely clinically. Thirty-five (61%) complete responders recurred with a median time to recurrence of 6 months. Twenty-six of the thirty-five patients who recurred had some component of local failure. The 22 complete responders who have not recurred have been followed a median of 13 months. Acute toxicity was minimal, with only 6 patients requiring interruption of therapy. Nine (13%) patients developed severe late complications and eight required surgery. The actuarial 5-year survival is 22%. This treatment regimen is disappointing in terms of both survival and local control.     

Double-Blind Prospective Comparative Trial between Foamed and Liquid Polidocanol and Sodium Tetradecyl Sulfate in the Treatment of Varicose and Telangiectatic Leg Veins

BACKGROUND: Twenty subjects were treated with either polidocanol (POL) or sodium tetradecyl sulfate (STS) to compare the efficacy and adverse sequelae of each agent. OBJECTIVE: To determine the safety and efficacy of two widely used sclerosing agents. METHODS: After the exclusion of saphenofemoral junction incompetency, each subject's leg veins were categorized by size (< 1, 1-3, and 3-6 mm in diameter). Each leg was then randomized to be treated with 0.5%, 1%, or 1% foam of POL or 0.25%, 0.5%, or 0.5% foam of STS according to vein size. An independent panel of four physicians, blinded to treatment, performed randomized photographic evaluations obtained pretreatment and 12 weeks post-treatment. Subject satisfaction index and overall clinical improvement assessment were also obtained. RESULTS: An average 83% improvement was noted for all vein sizes in all subjects with both POL and STS after a single treatment. Subjects were satisfied with treatment, regardless of the sclerosing agent used or the vein size treated. There was no statistically significant difference in adverse effects between each group. CONCLUSION: Both POL and STS are safe and effective sclerosing agents in the treatment of varicose and telangiectatic leg veins. Both are very tolerable and demonstrate similar post-treatment sequelae.     

Geometric Resistance and Microvascular Network Architecture of Human Colorectal Carcinoma

Objective : To measure the geometric resistance to blood flow in human colorectal carcinoma. Although tumor blood flow is of central importance in both the detection and the treatment of cancer, the determinants of blood flow through the neoplastic circulation are poorly understood. Methods : Human colorectal carcinomas (tissue weight = 272 g ± 43 g (SD), n = 6) were perfused ex vivo with a buffered physiological salt solution of known viscosity at flow rates ranging from 2.5 to 40 ml/min and perfusion pressures from 8 to 100 mm Hg. The geometric resistance was determined from the slope of the pressure-flow curve. For examination of the principal determinant of geometric resistance, the vascular architecture, one of the tumors was perfused with Batson's No. 17 polymer and macerated in KOH to produce a positive vascular cast that was used for measurement of vascular branching patterns and dimensions. Results : The pressure-flow relationship was linear at perfusion pressures above 40 mm Hg, and the geometric resistance, z₀, was constant at approximately 6.5 ± 10⁹g/cm³. Below 40 mm Hg, z₀ increased rapidly. The architecture of the arteriolar and capillary networks of human colorectal carcinoma is similar to those of experimental rodent tumors. Capillaries in planar and nonplanar mesh-works had mean segment diameters of 11 ± 2 and 9.6 ± 2 μm, lengths of 46 ± 24 and 107 ± 40 μm, and intercapillary distances of 46 ± 13 and 74 ± 24 μm, respectively. Conclusions : The geometric flow resistance in neoplastic tissue is 1–2 orders of magnitude higher than that observed in normal tissues. A decrease in functional vascular cross-sectional area may explain the additional increase in resistance at small perfusion pressures. The observed flow resistance may be due to the specialized arteriolar and capillary network architecture, pressures exerted by proliferating cancer cells, and/or coupling between vascular and extravascular flow. These observations demonstrate that tumor vascularity alone may not be indicative of flow resistance or tumor susceptibility to blood-borne therapeutic agents.     

Can marital selection explain the differences in health between married and divorced people? From a longitudinal study of a British birth cohort

In view of the rising divorce rates, the impact of divorce on health has an increasing importance in public health. The differentials in health between the married and the divorced may be explained by ‘marital selection’ and ‘marital protection’. Using longitudinal data from a study of the 1958 British birth cohort, factors that select people into divorce were identified from the areas of socio-economic status, health, and attractiveness, which included physical attractiveness, health-related behaviour and temperament. Evidence for both positive and adverse selection is found. The different sets of selection factors for females and males appear to be in line with gender role expectations. The health differentials between married and divorced men were weak and can be explained away by the selection factors. Having controlled for the selection effects, there were still significant associations between divorce and physical and psychological health in women. Though these unexplained differentials cannot be definitely interpreted as the consequences of marital dissolution, this interpretation remains plausible.     

Iatrogenic oesopha-geal perforation due to tracheal or naso-gastric intubation

Oesophageal perforation, due to a difficult endotracheal or nasogastric intubation occurred in a 49-year-old female. Perforation of the oesophagus is a rare complication of intubation of the trachea or oesophagus. Endotracheal intubation alone is most often blamed for iatrogenic oesophageal trauma following surgery. The incidence of iatrogenic oesophageal trauma is similar after nasogastric or endotracheal intubation. Iatrogenic oesophageal perforation occurs principally over the crico-pharyngeus muscle on the posterior wall of the oesophagus. Here the oesophagus is thin and is markedly narrowed. Contamination of the perioesophageal space with gastric contents leads to diffuse cellulitis and infection. Diagnosis is made by evidence of cervical subcutaneous emphysema, cervical pain, dysphagia, temperature elevation and leukocytosis. Plain roentenograms of the neck and a contrast media swallow will confirm the diagnosis. Treatment consists of massive antibiotic therapy followed by surgical repair and drainage of the area. Mortality ranges from 10-15 per cent with early diagnosis to 50 per cent if surgery is delayed.     

Assessment of vascularity in breast carcinoma by computer-assisted video analysis (CAVA) and its association with axillary lymph node status

Case-control methodology was used to evaluate the significance of vascularity in small breast carcinomas with regard to the presence or absence of axillary lymph node metastases. Vascularity was assessed in 32 axillary node positive primary breast tumours (LN+ve) less than 2 cm in size and compared with 56 control axillary node negative primary tumours (LN–ve), which were matched for histological type and grade and tumour size. This study design employed computer-assisted video analysis (CAVA) to assess the total blood vessel perimeter (BVP), total blood vessel area (BVA), and total blood vessel density (BVD) throughout a tissue section that encompassed an entire cross section of the tumour and its immediate periphery. The BVA and BVD in these tumours were not significantly different between LN+ve and LN–ve groups. The LN–ve carcinomas had, on average, a significantly (P < 0.05) higher total BVP (3355 µm/mm²) than LN+ve tumours (2771 µm/mm²). 'Hot spot' areas were also independently assessed by two pathologists and the same areas measured by CAVA. A strong correlation (P < 0.001) between the two methods of assessment of BVD of the neovascular 'hot spots' was found; however, no association with axillary lymph node metastasis was found using either method of assessment. In conclusion, vascularity assessed by either blood vessel density or blood vessel size in primary invasive breast cancers less than 2 cm in diameter showed no association with axillary lymph node metastasis; in fact a negative association was found with total BVP of whole tumour sections and BVD in 'hot spots' using CAVA. Further, this study has established a computer-assisted method of quantifying vascularity in solid neoplasms and is a positive step towards a standardised approach to this diverse and methodologically variable area.     

FDA relations during drug development

Working closely and cooperatively with regulatory authorities during drug development is vital to successful drug development programs. In the United States, the drug development team includes not only members of the key disciplines of drug discovery, clinical research, regulatory affairs, marketing, chemistry, toxicology, and legal aspects, but also the Food and Drug Administration (FDA). New regulations encourage meetings at the pre-investigational new drug (pre-IND), end-of-phase-2, and pre-new drug application (pre-NDA) submission phases. Appropriate informal discussions via fax and telephone are also encouraged. By proactively interacting with the FDA, the pharmaceutical industry increases the probability of a successful drug development program.