Surgical treatment of nasopharyngeal cancer - a consensus recommendation from two Chinese associations.

BACKGROUND: Surgical treatment is playing an increasingly important role in the management of nasopharyngeal carcinoma (NPC). This consensus focuses on the indications for optimal surgery, and surgical methods in the whole process of treatment for NPC to provide a useful reference to assist these difficult clinical decisions. METHODOLOGY: A thorough review of available literature on NPC and surgery was conducted by the Association for the prevention and treatment of nasopharyngeal carcinoma in China, international exchange and promotion Association for medicine and healthcare, and the Committee on nasopharyngeal cancer of Guangdong provincial anticancer association. A set of questions and a preliminary draft guideline was circulated to a panel of 1096 experienced specialists on this disease for voting on controversial areas and comments. A refined second proposal, based on a summary of the initial voting and different opinions expressed, was recirculated to the experts in two authoritative medical science and technology academic groups in the prevention and treatment of NPC in China for review and reconsideration. RESULTS: The initial round of questions showed variations in clinical practice even among similar specialists, reflecting the lack of high-quality supporting data and resulting difficulties in formulating clinical decisions. Through exchange of comments and iterative revisions, recommendations with high-to-moderate agreement were formulated on general treatment strategies and details of surgery, including indications and surgical approaches. CONCLUSION: By standardizing the surgical indications and practice, we hope not only to improve the surgical outcomes, but also to highlight the key directions of future clinical research in the surgical management of NPC.

Astragalus membranaceus root supplementation improves average daily gain, rumen fermentation, serum immunity and antioxidant indices of Tibetan sheep.

The use of antibiotics as supplements in animal feed is restricted due to possible health hazards associated with them. Consequently, there is increasing interest in exploiting natural products to improve health and production of livestock with no detrimental side effects. In this study, we examined the effect of Astragalus membranaceus root (AMT) supplementation on DM intake, growth performance, rumen fermentation and immunity of Tibetan sheep. Twenty-four male Tibetan sheep (31 ±â€¯1.4 kg; 9 months old) were assigned randomly to one of four dietary treatments with different levels of AMT: 0, 20, 50 and 80 g/kg DM (A0, A2, A5 and A8, respectively) in addition to their basal diets. A0 acted as a control group, and measurements were recorded over a 56-d feeding period. Sheep fed with AMT had a higher average daily gain and a lower feed:gain ratio than controls (P < 0.001). Rumen concentrations of NH3-N (P < 0.001), total volatile fatty acids (P = 0.028), acetate (P = 0.017) and propionate (P = 0.031) in A5 and A8 were higher than those in A0. The addition of AMT in the feed significantly increased serum antioxidant and immunity factors of the sheep and increased the concentrations of serum interleukin, immunoglobulin and tumour necrosis factor-α (P = 0.010). We concluded that AMT can be used as a feed additive to improve growth performance and rumen fermentation and enhance the immunity of Tibetan sheep. Some responses exhibited a dose-dependent response, whereas other did not exhibit a pattern, with an increase in AMT. The addition of 50 and 80 g/kg AMT of total DM intake showed the most promising results.

Quantifying climate and management effects on regional crop yield and nitrogen leaching in the north china plain.

Better water and nitrogen (N) management requires better understanding of soil water and N balances and their effects on crop yield under various climate and soil conditions. In this study, the calibrated Root Zone Water Quality Model (RZWQM2) was used to assess crop yield and N leaching under current and alternative management practices in a double-cropped wheat ( L.) and maize ( L.) system under long-term weather conditions (1970-2009) for dominant soil types at 15 locations in the North China Plain. The results provided quantitative long-term variation of deep seepage and N leaching at these locations, which strengthened the existing qualitative knowledge for site-specific management of water and N. In general, the current management practices showed high residual soil N and N leaching in the region, with the amounts varying between crops and from location to location and from year to year. Seasonal rainfall explained 39 to 84% of the variability in N leaching (1970-2009) in maize across locations, while for wheat, its relationship with N leaching was significant ( < 0.01) only at five locations. When N and/or irrigation inputs were reduced to 40 to 80% of their current levels, N leaching generally responded more to N rate than to irrigation, while the reverse was true for crop yield at most locations. Matching N input with crop requirements under limited water conditions helped achieve lower N leaching without considerable soil N accumulation. Based on the long-term simulation results and water resources availability in the region, it is recommended to irrigate at 60 to 80% of the current water levels and fertilize only at 40 to 60% of the current N rate to minimizing N leaching without compromising crop yield.

Dose escalation of three-dimensional conformal radiotherapy for locally recurrent nasopharyngeal carcinoma: a prospective randomised study.

AIMS: To investigate prospectively the feasibility and efficacy of dose escalation using three-dimensional conformal radiotherapy (3D-CRT) boost technique for locally recurrent nasopharyngeal carcinoma (NPC) in a randomised study. MATERIALS AND METHODS: Thirty-six patients with locally recurrent NPC (>6 months interval from previous radical radiotherapy, no cervical lymph-node involvement and no distant metastasis) were enrolled. Treatment included conventional external-beam radiotherapy to 54 Gy, followed by a 3D-CRT boost to the gross tumour region. Patients were randomised to three boost dose levels: 16 Gy, 20 Gy and 24 Gy for groups I, II and III, respectively, with 12 patients in each group. All boost doses were delivered in 4-Gy fractions and 3 fractions per week. Median follow-up was 27 months (range 14-44 months). RESULTS: Three-year, local-recurrence-free survival rate was significantly higher (72%) for the high-dose group III than for groups I and II (37% and 28%, respectively, P = 0.047). No significant difference was found in the 3-year overall survival rate among the three groups (72%, 59% and 82% for groups I, II and III, respectively). Three-year distant metastases rates were 17%, 0% and 18%, respectively. Skull-base invasion (P = 0.017) and pathology (P = 0.0006) correlated with overall survival. Treatment was well tolerated and no significant difference was observed among the three groups in acute and late toxicities (grade III toxicity is minimal: 17%, 17%, 0% of oral mucositis and 25%, 17%, 17% of nasopharyngeal mucositis in groups I, II, III, respectively, and 8% leukocytopenia only in group II; no grade IV toxicity occurred in any of the groups except for a fatal bleeding in group III). CONCLUSIONS: Re-irradiation with high-dose 3D-CRT boost technique results in high local control rate and acceptable toxicity in patients with recurrent NPC. Dose escalation to the boost volume to 78 Gy (54 Gy + 24 Gy boost) results in improved recurrence-free survival compared with lower doses.

Evaluation of the clinical utility of the ultrasensitive immunofluometric assay for growth hormone (GH) and of the cortisol secretory pattern in prediction of the linear growth response to treatment with GH.

OBJECTIVES: To evaluate the utility of an ultrasensitive IFMA for human 22 kDa GH in assessment of GH secretion and prediction of the linear growth response to exogenous GH. METHODS: Utilizing Delfia reagents supplied by Wallac-OY, an ultrasensitive IFMA for GH was established. Serum GH concentrations from 15 children/adolescents undergoing 24 hour GH secretory profiles with sampling at 20 minute intervals were analyzed by both IFMA and RIA. Cortisol values were also measured. Twelve children were later treated with GH. The 24 hour GH and cortisol secretory profiles were analyzed by the Cluster program and the relationships of these profiles to the linear growth response to exogenous GH determined. RESULTS: The sensitivity of the IFMA for GH relative to a zero standard was 0.005 ng/ml; intra-assay coefficients of variation ranged from 12% at a GH concentration of 0.005 ng/ml to 4% at 0.038 ng/ml; interassay coefficients of variation ranged from 34% at a GH concentration of 0.005 ng/ml to 10.5% at 2.7 ng/ml and to 2.7% at 12.7 ng/ml. Above assay sensitivity, there was good correlation between GH concentrations determined by IFMA and those by IRMA and RIA (r = 0.998 and 0.992 respectively). The number of GH secretory peaks identified by IFMA was significantly greater than that detected by RIA (10.6 +/- 3.2 [SD] vs 6.7 +/- 3.3/24 hours, p = 0.0001 by paired t-test). There were few significant relationships between any parameter of GH secretion measured by RIA or IFMA (peak GH pulse amplitude, percent increase in amplitude, area under the peak, interpeak interval) and the pretreatment growth rate, the growth velocity while receiving GH therapy, or the increment in growth rate during administration of GH. The number of GH secretory peaks determined by RIA correlated weakly with the pretreatment growth rate. There was no meaningful relationship between the serum concentrations of cortisol and GH-IFMA. Peak GH concentrations and nadir cortisol values were exactly coincident in 15.7% (25/159); 42.8% of nadir cortisol values coincided with or were within +/- 20 minutes of peak GH values (68/159). However, there was no relationship between the number of cortisol secretory peaks, the pooled 24 hour and nocturnal concentrations of cortisol and the pretreatment growth velocity, the growth rate or increment in growth velocity during administration of GH. CONCLUSIONS: Despite the increased sensitivity of the IFMA and its ability to detect pulsatile GH secretion heretofore unidentified, data from this GH assay were not useful in predicting first year growth rate during administration of GH. The secretory pattern of cortisol was not helpful in predicting the growth response to GH.

Neurotransmitter control of growth hormone secretion in children after cranial radiation therapy.

Cranial radiation for childhood cancer can cause growth hormone deficiency (GHD), usually due to hypothalamic rather than pituitary dysfunction. To investigate whether this hypothalamic dysfunction is secondary to altered neurotransmitter input from other brain centers, we used neurotransmitter-excitatory substances to study the GH secretory response in 17 children who had received 12 to 60 Grey (Gy) to the cranium and 40 short children with normal endocrine function. As expected, the irradiated children had decreased mean GH secretion in response to insulin-induced hypoglycemia and arginine infusion, and decreased mean 24 hour GH concentrations, compared to the control group. In contrast, the two groups had similar GH secretory responses to GHRH stimulation and somatostatin suppression. Assessment of neurotransmitter pathways in the irradiated children revealed significantly lower mean peak GH concentrations in response to 5 of the 6 substances tested compared to control children: alpha-adrenergic stimulation (clonidine), beta-adrenergic blockade (propranolol), cholinergic stimulation, dopaminergic stimulation (L-dopa), and GABA-ergic stimulation (valproic acid). Results of serotonergic stimulation (L-tryptophan) were not statistically significant. Eleven patients who had abnormal GH secretion underwent 4 or more tests with neurotransmitter-stimulatory agents; 3 patients had peak GH concentrations of < 2.5 micrograms/l to all tests, whereas 4 patients had a peak GH concentration of > or = 7 micrograms/l to one or more tests but < 5 micrograms/l to one or more other tests. These observations suggest that radiation damage may sometimes spare growth hormone-releasing hormone (GHRH) and somatostatin secretion while affecting neurotransmitter pathways. We postulate that the hierarchy of sensitivity to radiation damage may be hypothalamic and extra-hypothalamic neurotransmitters > hypothalamic GHRH and/or somatostatin secretion > pituitary GH secretion.

Effects of coadministered growth hormone (GH)-releasing hormone and GH-releasing hexapeptide on maladaptive aspects of obesity in Zucker rats.

The purpose of this study was to determine the effect of chronic pharmacological stimulation of the pituitary gland on GH hyposecretion and other maladaptive aspects of obesity. Obese Zucker rats were coadministered GH-releasing hormone (GHRH; 3 micrograms/kg) and GH-releasing hexapeptide (GHRP-6; 300 micrograms/kg), a potent combination of synergistic GH secretagogues, once daily for 60 consecutive days. Although pituitary weights and GH concentrations were higher in obese rats administered the peptides than in obese rats administered saline, stimulated GH secretion was lower in obese rats than in lean rats. However, compared to those in lean rats, plasma insulin-like growth factor-I and insulin concentrations were higher in the obese rats regardless of treatment. The GH secretagogues did not alter food intake or body weight gain in sexually mature obese rats, whereas body weight gain was significantly increased when they were administered to prepubertal obese rats. Although glucose tolerance was impaired in both groups of obese rats, it improved in obese rats administered GHRH and GHRP-6 compared to that in obese rats administered saline. On the other hand, plasma cholesterol concentrations were elevated in obese rats administered the GH secretagogues but not saline. In conclusion, the results of this study suggest that hyposensitivity to GHRH and GHRP-6 in obese Zucker rats results from high concentrations of plasma insulin-like growth factor-I that negatively feedback on stimulated GH secretion. Nonetheless, daily episodes of endogenous GH secretion resulting from chronic coadministration of GH secretagogues significantly influenced the pituitary gland as well as lipid and carbohydrate metabolism.

Effects of short-term growth hormone therapy in rats undergoing 75% small intestinal resection.

Thirty 250-g male rats underwent 75% small intestinal resection and received s.c. injections of water [short gut (SG)-control], human growth hormone (hGH) at 0.1 mg/kg/dose [SG-low-dose (LD) GH], or hGH at 1.0 mg/kg/dose [SG-high-dose (HD) GH] every other day for 28 days. Ten additional rats underwent sham operation and received water injections (sham control). After 28 days, SG-control and SG-LDGH rats weighed significantly less than the sham control group; the mean weight of the SG-HDGH group was not different from other groups. Weight per centimeter of the distal ileum was greater in all SG groups compared to the sham control group, and was greater in the SG-HDGH than in the SG-control group. Mean mucosal height of the distal ileum was greater in both SG groups receiving GH than in sham controls. No differences in ileal mucosal DNA content or ileal insulin-like growth factor-1 (IGF-1) content were identified between groups. Mucosal sucrase activity was not increased in hGH-treated rats. Serum calcium and phosphorus concentrations were higher in SG-HDGH rats than in SG-control animals. HDGH increased body weight, distal ileal weight/cm, and mucosal height in rats undergoing 75% small bowel resection. A trend toward normalization of serum calcium, phosphorus, and plasma IGF-1 concentrations was also observed. Further longer-term studies are indicated to learn if GH has a beneficial effect upon gut growth and function in the SG syndrome.

Linear growth response to exogenous growth hormone in children with short stature.

Response to growth hormone (GH) therapy was evaluated in 38 short children (28 males and 10 females; less than 1% in height for chronologic age [CA]) who were clinically categorized into three groups based on their endogenous mean 24-hour GH concentration (mean 24-hour GH) and peak GH response to two or more provocative agents (peak GH). All patients were treated with biosynthetic somatropin (human growth hormone) (0.15 to 0.30 mg/kg per week) injected subcutaneously three to seven times per week for a mean duration of 12.5 months. Group 1 consisted of 17 subjects (CA, 12.5 +/- 2.9 years [mean +/- SD]; bone age, 9.4 +/- 2.9 years; height velocity [HV], 3.4 +/- 1.8 cm/y; peak GH, 5.8 +/- 2.6 micrograms/L; mean 24-hour GH, 1.7 +/- 0.6 micrograms/L; and insulinlike growth factor-I, 0.40 +/- 0.24 U/mL. Group 2 consisted of 10 subjects (CA, 11.7 +/- 2.7 years; bone age, 9.2 +/- 3.0 years; HV, 3.4 +/- 1.6 cm/y; peak GH, 16.4 +/- 5.2 micrograms/L; mean 24-hour GH, 1.7 +/- 0.5 micrograms/L; and insulinlike growth factor-I, 0.49 +/- 0.27 U/mL. Group 3 consisted of 11 subjects (CA, 12.7 +/- 2.2 years; bone age, 10.2 +/- 2.4 years; HV, 3.5 +/- 1.5 cm/y; peak GH, 22.5 +/- 8.6 micrograms/L; mean 24-hour GH, 3.8 +/- 1.1 micrograms/L; and insulinlike growth factor-I, 1.07 +/- 0.69 U/mL. Following administration of somatropin, an increase (delta) in HV of 2.0 cm/y or greater occurred in 94% (16/17) of the group I subjects (delta HV of 5.1 +/- 2.6 cm/y), in 90% (9/10) of the group 2 subjects (delta HV of 4.3 +/- 2.2 cm/y), and in 73% (8/11) of group 3 subjects (delta HV of 3.7 +/- 2.3 cm/y). However, regardless of provoked and/or endogenous GH secretory dynamics, 88% of the children whose pretreatment HV was 2.0 cm/y or less, 94% whose pretreatment HV was between 2.0 and 4.0 cm/y, and 79% whose pretreatment HV was greater than 4.0 cm/y increased their HVs to 2.0 cm/y or greater while they were receiving somatropin. Significant negative correlations were observed between delta HV and pretreatment HV (r = -.67), delta HV and GH concentration expressed as a 24-hour area under the curve (r = -.33), and delta HV and peak GH (r = -.34).(ABSTRACT TRUNCATED AT 400 WORDS)

Pooled prolactin measurements in the evaluation of short children.

PRL secretion was determined in 63 children undergoing evaluation of GH status. Children were assigned to 1 of 3 groups based on GH studies: group 1, those with abnormal GH responses to provocative testing (n = 23); group 2, children with normal GH responses to provocative testing and mean 24-h GH concentrations below 2.5 micrograms/L (n = 14); or group 3, those with normal stimulated GH secretion and mean 24-h GH concentrations of 2.5 micrograms/L or more (n = 26). Serum PRL concentrations were measured in daytime (0800-1600 h), nighttime (2200-0600 h), and 24-h pools of serum specimens obtained every 20 min over a 24-h period. Mean (+/- SD) daytime (17.5 +/- 14.3 micrograms/L) and 24-h (19.2 +/- 13.0 micrograms/L) pool PRL concentrations were significantly higher in group 1 than in group 3 (daytime, 6.7 +/- 2.3; 24 h, 10.2 +/- 2.5 micrograms/L; P less than 0.01). Mean nighttime pool PRL concentrations did not differ among groups. Mean nighttime pool PRL values were significantly higher (P less than 0.01) than daytime pool values in group 3 (nighttime pool, 13.6 +/- 3.6 micrograms/L; night to day ratio, 2.2 +/- 1.0) and group 2 (16.8 +/- 9.0 micrograms/L; night to day ratio, 2.5 +/- 1.5), but not within group 1 (21.4 +/- 13.5 micrograms/L; night to day ratio, 1.4 +/- 0.5). The mean peak and increment in PRL concentrations after an iv bolus of insulin-TSH-LHRH were not different among groups. The mean decrement in serum PRL level after L-dopa ingestion was greater in group 1 than in group 3 (P less than 0.05). Two children in group 2 and 10 in group 1 had significantly elevated daytime pool PRL concentrations (greater than 11.3 micrograms/L; 2 SD above the mean value for group 3). Two additional children in group 2 and 2 in group 1 had elevated 24-h (greater than 15.2 micrograms/L) pool PRL concentrations. One child in group 2 and 3 in group 1 had low 24-h PRL concentrations (less than 5.2 micrograms/L; less than 2 SD below the mean of group 3). Fourteen of 20 children with elevated daytime and/or 24-h pool PRL levels or low 24-h pool PRL values had structural or radiation-associated insults to the hypothalamic-pituitary axis evident in the history or with brain-imaging techniques; 1 had microphallus with panhypopituitarism and 5 children had no structural abnormalities.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of drug and alcohol abuse upon pituitary-testicular function in adolescent males.

To assess the effects of drug and alcohol abuse (DAA) on the physical changes and hormones of puberty in adolescents, 26 males (13 5/12-22 years) enrolled in a drug rehabilitation program were examined. In 22 subjects four timed blood samples were obtained sequentially at 15 minute intervals for measurement of serum concentrations of testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH) and dehydroepiandrosterone sulfate (DHAS). The mean duration of DAA was 3.7 years, with marijuana and alcohol being the most frequently abused substances. The study subjects were compared to a matched control group of non-substance-abusing teenagers. All heights and weights of the DAA subjects fell within two standard deviations of the mean on the Tanner Growth Charts and no statically significant differences in the Tanner stages of sexual maturation were found between the DAA and control groups. The mean (+/- SD) testosterone level of the DAA group (221 +/- 109 ng/dl) was less than half that of the control group (477 +/- 193 ng/dl, p less than 0.001). Mean LH concentration in the DAA group (3.9 +/- 3.0 mIU/ml) was significantly less than that of the control group (10 +/- 4.9 mIU/ml, p less than 0.01). In both the DAA and control populations there was a significant (p less than 0.01) correlation between serum concentrations of LH and testosterone. The mean FSH level of the DAA group (3.3 +/- 1.1 mIU/ml) was significantly less (p less than 0.02) than that of the control group (4.7 +/- 1.9 mIU/ml). To assess the effects of treatment, six boys underwent repeat blood sampling 7-12 months after drug and alcohol withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)

Isolation of Vibrio cholerae from the American Eel, Anguilla rostrata.

Nineteen eels ( Anguilla rostrata ), collected from the Suwannee River estuary in Florida, were examined for Vibrio cholerae . Nonagglutinable V. cholerae were isolated from 11 of the eels for an isolation rate of 58%. Isolates from 6 of the eels were confirmed by the Smith serotyping system and found to be types 17, 68 and 175.