Extracapsular extension in oral cavity cancers-predictive factors and impact on recurrence pattern and survival.

Extracapsular extension (ECE) has long been considered a poor prognostic factor in oral cavity cancer, the presence of which warrants intensification of adjuvant therapy. This study was done to analyze the survival of patients with ECE who received adjuvant chemoradiation. Patients with pathologically confirmed squamous cell carcinoma of the oral cavity, with a minimum of 2 years of follow-up, who were treated at a tertiary cancer centre in New Delhi, India during the years 2009-2017, were included. On multivariate analysis, ECE was significantly associated with depth of invasion >10 mm and tumour deposit size >5 mm. Among the node-positive group, patients without ECE had a 5-year disease-free survival (DFS) and 5-year overall survival (OS) advantage over ECE-positive patients of 7.8% (63.8% vs. 56.0%) and 16.5% (87.2% vs. 70.7%), respectively. For patients with ECE, the hazard ratio for DFS and OS was 1.3 (95% confidence interval 0.97-1.75, P = 0.078) and 2.30 (95% confidence interval 1.35-3.92, P = 0.002), respectively. ECE remains one of the strongest predictors of recurrence and survival in oral cancer patients, and despite aggressive adjuvant therapy, distant recurrence is still significantly high.

Spectrum and diagnosis of idiopathic pulmonary fibrosis.

OBJECTIVE: To study the clinical profile of patients with idiopathic pulmonary fibrosis (IPF) and methods used for diagnosis. METHODS: Prospective analysis of symptoms, signs, radiology and lung biopsy of patients freshly diagnosed to have IPF over a 16-month period. RESULTS: During the study period, 76 patients (35 men) with a mean age of 50.6 +/- 11.9 years were diagnosed to have IPE Breathlessness (98.6%) and dry cough (92.1%) were the most common presenting symptoms. Transbronchial lung biopsy (TBLB) was performed in 38 (50%) patients. Histopathological examination revealed features consistent with IPF in 35 (92.1%) patients; two of the remaining three patients underwent open lung biopsy. Other patients were diagnosed based on clinical features and high resolution chest tomography (HRCT) findings. HRCT was performed in 69 (90.8%) patients; all had features suggestive of diffuse interstitial fibrosis. CONCLUSION: IPF is diagnosed more commonly now than in the past. Indian patients may be developing the disease a decade earlier than their counterparts in the West. TBLB and HRCT are useful in establishing diagnosis. IPF should be considered a distinct clinical entity rather than a diagnosis of exclusion.

Impaired growth and elevated fas receptor expression in PIGA(+) stem cells in primary paroxysmal nocturnal hemoglobinuria.

The genetic defect underlying paroxysmal nocturnal hemoglobinuria (PNH) has been shown to reside in PIGA, a gene that encodes an element required for the first step in glycophosphatidylinositol anchor assembly. Why PIGA-mutated cells are able to expand in PNH marrow, however, is as yet unclear. To address this question, we compared the growth of affected CD59(-)CD34(+) and unaffected CD59(+)CD34(+) cells from patients with that of normal CD59(+)CD34(+) cells in liquid culture. One hundred FACS-sorted cells were added per well into microtiter plates, and after 11 days at 37 degrees C the progeny were counted and were analyzed for their differentiation pattern. We found that CD59(-)CD34(+) cells from PNH patients proliferated to levels approaching those of normal cells, but that CD59(+)CD34(+) cells from the patients gave rise to 20- to 140-fold fewer cells. Prior to sorting, the patients' CD59(-) and CD59(+)CD34(+) cells were equivalent with respect to early differentiation markers, and following culture, the CD45 differentiation patterns were identical to those of control CD34(+) cells. Further analyses of the unsorted CD59(+)CD34(+) population, however, showed elevated levels of Fas receptor. Addition of agonist anti-Fas mAb to cultures reduced the CD59(+)CD34(+) cell yield by up to 78% but had a minimal effect on the CD59(-)CD34(+) cells, whereas antagonist anti-Fas mAb enhanced the yield by up to 250%. These results suggest that expansion of PIGA-mutated cells in PNH marrow is due to a growth defect in nonmutated cells, and that greater susceptibility to apoptosis is one factor involved in the growth impairment.

Fluoride balances during early and late pregnancy.

Information useful in estimating the occupational fluoride hazard to pregnant women is scanty. Fluoride excretion and balances were determined in 18 young women--seven who were not pregnant, six in early pregnancy (second quarter), and five in late pregnancy (fourth quarter)--over a 20-day period under confined metabolic conditions. The total fluoride intake averaged 1.35 mg/day (0.35 mg from the diet, 1 mg from a mineral capsule). Urinary fluoride excretion levels for the three groups were similar and averaged 0.95, 1.03, and 1.15 mg/day, respectively. On the average, 88% of the total fluoride excreted was in the urine and the remainder in the feces. With few exceptions, the women in each group demonstrated small positive balances; the averages were +0.19, +0.16, and +0.14 mg/day, respectively. The differences were small and not statistically significant (p greater than 0.1). These data indicate that fluoride metabolism is not markedly altered during the course of pregnancy.

Effect of dichloromethylene diphosphonate on fluoride balance in healthy men.

Healthy men with a daily intake of 0.37 mg fluoride were given dichloromethylene diphosphonate (Cl2MDP) or a placebo during a period of ambulation followed by bed rest. In both groups, serum ionic fluoride was unchanged, and fluoride balances were negative, but Cl2MDP significantly reduced loss of fluoride in the treated groups.

Fluoride balance studies in healthy men during bed rest with and without a fluoride supplement..

In a program of studies of disuse osteoporosis, fluoride balances were determined in healthy men during ambulation and then during bed rest for 6 to 17 wk. Control subjects ingested basal diets containing 0.4 mg fluoride per day, whereas experimental subjects received 10-mg fluoride supplements in divided doses with meals. Fluoride and calcium were measured in diets, urine, and feces. Serum analyses included calcium and ionic fluoride. Fluoride balances during both phases were uniformly negative in control subjects (mean -0.46 mg/day) but uniformly positive in supplement subjects (mean +2.58 mg/day). Calcium balances were markedly negative during bed rest in both groups. Serum fluoride concentrations increased proportionally to fluoride intake, averaging 0.016 ppm in the controls and 0.045 ppm in the supplement subjects. The supplement of 10 mg fluoride daily did not protect against bed rest-induced calcium loss, or cause any clinical or laboratory abnormality in any subject.

Fluoride balance studies in ambulatory healthy men with and without fluoride supplements.

Fluoride balances were determined in healthy adult males under metabolic ward conditions. This is the first fluoride study to use the diffusion method in exploring the balances of subjects ingesting basal (i.e., everyday) diets with deionized water for cooking and drinking. Certain groups were given daily supplements of 5 or 10 mg. fluoride as sodium fluoride in divided doses with meals. Fluoride was measured in the diets, sodium fluoride tablets, urine, feces, and serum. Approximately 90% of the fluoride excreted was found in the urine and the remainder in the feces in all groups. In the control subjects, fluoride balances were uniformly negative (mean of -0.40 mg/day); in contrast, balances were uniformly positive (mean of +1.38 and +2.88 mg/day, respectively) in subjects receiving 5 or 10 mg F supplements daily. Serum ionic fluoride concentration increased proportionally to fluoride intake and averaged 0.016, 0.029, and 0.040 ppm in the control, 5-mg and 10-mg groups, respectively. These fluoride supplements did not cause any clinical or laboratory abnormality in any subjects.

Fluoride balances in pregnant and nonpregnant women.

In planning health protection for pregnant as well as nonpregnant women exposed to fluorides, information about their fluoride metabolism is essential. The authors determined fluoride balances in small groups of young women maintained on two different low-fluoride diets for one or two 21-day periods in a metabolic unit. One diet contained an average of 0.41 mg F/day, and the other contained an average of 0.27 mg F/day. Excretion of fluoride in pooled three-day collections for each subject was about 80% in the urine and 20% in the feces. Pregnant (last half of term) and nonpregnant women demonstrated small negative fluoride balances; the averages were about -0.32 mg F/day and -0.15 mg F/day, respectively. Similar values have been found for young males in other studies. Pregnancy in these subjects did not markedly alter normal fluoride metabolism.