Subtalar Joint Distraction Arthrodesis Utilizing a Titanium Truss: A Case Series.

Subtalar joint distraction arthrodesis has been recommended for the treatment of conditions such as nonunion or malunion of subtalar joint arthrodesis posttraumatic arthritis. Both conditions are difficult to treat, because the deformities created in the frontal and sagittal planes of these conditions are complex. If these malalignments are not addressed, ankle joint instability and wear occur over time. In general, either autograft or allograft bone has been used to perform distraction arthrodesis of the subtalar joint. Although studies have shown successful use, there have been complications. Autografts have resulted in donor site morbidity and limitations on graft size, and allografts have shown high nonunion rates. Both autografts and allografts have shown graft collapse over time. Recent literature has discussed the use of tantalum technology to span large defects in bone healing. Studies have shown that tantalum provides superior strength and bone incorporation compared with autografts and allografts. This case series presents 2 cases in which tantalum truss technology was used for distraction arthrodesis. Although this series is limited in patient numbers, both cases show effective graft incorporation with no loss in height over time and earlier return to activity compared with previous studies that used autograft and allograft wedges.

Underage drinking, group identity and access to alcohol: a qualitative study of Chinese youths.

Despite substantial research into underage youth's source of alcohol, few studies have examined how they go about obtaining alcohol through various means. This study explored the nature of alcohol access by Chinese adolescents and how their own perceptions around alcohol availability influence them to source alcohol in particular ways. This research involved focus groups with 111 young people aged 14-17 in Hong Kong, China. A grounded theory analysis was conducted using NVivo 10. While participants perceived ease of obtaining alcohol from retail outlets, proxy purchasing through friendship group members was reported as routine experience primarily to avoid potential embarrassment of being turned away. Convincing vendors that they were of legal drinking age was the convention used most commonly by Chinese teen drinkers. Participants expressed resentment toward adults who were willing to supply minors with alcohol. Nevertheless, this feeling of disappointment did not alter the ways they sourced alcohol. Access activities embodied a symbol of group identity in the collectivist Chinese culture. Results suggest that greater consideration should be given to understanding the complex interplay between alcohol access and community experience within peers. The perceived importance of face saving in Chinese culture may provide avenues for preventing youth access to alcohol.

Gating of the cardiac Ca2+ release channel: the role of Na+ current and Na(+)-Ca2+ exchange.

In cardiac myocytes, calcium influx through the calcium channel is the primary pathway for triggering calcium release. Recently it has been suggested that the calcium-induced calcium release mechanism can also be activated indirectly by the sodium current, which elevates the sodium concentration under the cell membrane, thereby favoring the entry of "trigger" calcium via the sodium-calcium exchanger. To test this hypothesis, sodium current was suppressed by reducing the external sodium concentration or applying tetrodotoxin. At potentials positive to -30 millivolts, calcium release was unaffected. A small calcium release at more negative potentials could be attributed to partial activation of calcium channels, because it was unaltered by replacement of sodium with lithium and was blocked by cadmium. Thus, sodium influx or its accumulation does not initiate calcium release. In addition, sodium-calcium exchange-related calcium release at potentials positive to +80 millivolts has slower kinetics than calcium channel-induced release. Therefore, only the calcium channel gates the fast release of calcium from the sarcoplasmic reticulum in the range of the action potential.

Clusterin plays an important role in hepatocellular carcinoma metastasis.

To identify genes associated with tumor metastasis in hepatocellular carcinoma (HCC), gene expression profiles between a pair of primary HCC (H2-P) and their matched metastatic HCC (H2-M) were compared. Overexpression of clusterin (CLU) was found in H2-M cells. To determine the roles CLU played in HCC metastasis, CLU was transfected into H2-P cells. Overexpression of CLU in H2-P cells increased cell migration by twofold in vitro and formation of metastatic tumor nodules in liver by eightfold in vivo. To evaluate the correlation of CLU expression with HCC metastasis, the expression levels of CLU in HCCs were investigated using a tissue microarray (TMA) containing 104 pairs of primary HCCs and their matched metastases. The frequency of CLU overexpression increased significantly in metastatic HCCs (59.1%) compared with that in primary tumors (32.6%, P<0.001). To gain additional insight into the function of CLU, the expression profile of H2P-CLU was compared with vector-transfected H2-P cells by cDNA microarray. A total of 35 upregulated and 14 downregulated genes were detected in H2P-CLU. One of the upregulated genes known as YKL-40, which is implicated in matrix-remodeling and metastasis, was further studied using TMA. A significant correlation (P<0.001) between the expression levels of YKL-40 and CLU was observed, implying that the CLU-YKL-40 pathway may play an important role in HCC metastasis.

Impaired physiological responses to chronic hypoxia in mice partially deficient for hypoxia-inducible factor 1alpha.

Chronic hypoxia induces polycythemia, pulmonary hypertension, right ventricular hypertrophy, and weight loss. Hypoxia-inducible factor 1 (HIF-1) activates transcription of genes encoding proteins that mediate adaptive responses to hypoxia, including erythropoietin, vascular endothelial growth factor, and glycolytic enzymes. Expression of the HIF-1alpha subunit increases exponentially as O2 concentration is decreased. Hif1a-/- mouse embryos with complete deficiency of HIF-1alpha due to homozygosity for a null allele at the Hif1a locus die at midgestation, with multiple cardiovascular malformations and mesenchymal cell death. Hif1a+/- heterozygotes develop normally and are indistinguishable from Hif1a+/+ wild-type littermates when maintained under normoxic conditions. In this study, the physiological responses of Hif1a+/- and Hif1a+/+ mice exposed to 10% O2 for one to six weeks were analyzed. Hif1a+/- mice demonstrated significantly delayed development of polycythemia, right ventricular hypertrophy, pulmonary hypertension, and pulmonary vascular remodeling and significantly greater weight loss compared with wild-type littermates. These results indicate that partial HIF-1alpha deficiency has significant effects on multiple systemic responses to chronic hypoxia.

Induction of matrix metalloproteinases by Epstein-Barr virus latent membrane protein 1 isolated from nasopharyngeal carcinoma.

Epstein--Barr virus latent infection is associated with human malignancies including Burkitt's lymphoma, gastric carcinoma and the highly invasive nasopharyngeal carcinoma (NPC). Increased expression of EBV latent membrane protein 1, LMP1, is correlated with tumor progression and metastasis in NPC. LMP1 induces cellular proteins including cytokines and matrix metalloproteinases (e.g., MMP1, MMP2 and MMP9). MMPs are endopeptidases involved in the degradation of extracellular matrix proteins; and their upregulation in cancer implicates their potential role in tumor metastasis. In light of the role of LMP1 in cytokine dysregulation and the fact that MMPs are regulated by cytokines, we examined whether LMP1 promotes NPC metastasis via the induction of MMPs. To delineate the oncogenic role of LMP1 in NPC, we first investigated the induction of MMP1, MMP2, MMP3 and MMP9 in LMP1-positive NPC tumor samples (n=15) by quantitative RT-PCR. We showed a significant induction of MMP1 and MMP3 transcripts in the EBV LMP1-positive NPC tissues, compared with biopsies obtained from the adjacent non-tumor tissues. To investigate the role of LMP1 in MMP expression in NPC, we cloned the LMP1 gene from NPC samples and transiently expressed it in MRC5 cells (human lung fibroblasts). Following transfection, a time-dependent elevation of endogenous MMP3 expression was found in the LMP1-transfectants by quantitative RT-PCR and Western analysis. Taken together, we observed that MMP3 is upregulated in LMP1-positive NPC tumors and LMP1-expression in fibroblasts is associated with MMP3 and cytokine expression. Our results suggest that LMP1 may contribute to invasiveness of NPC cells via the expression of MMP3 in fibroblasts.

Normal Tissue Complication Probability (NTCP) Modelling of Severe Acute Mucositis using a Novel Oral Mucosal Surface Organ at Risk.

AIMS: A normal tissue complication probability (NTCP) model of severe acute mucositis would be highly useful to guide clinical decision making and inform radiotherapy planning. We aimed to improve upon our previous model by using a novel oral mucosal surface organ at risk (OAR) in place of an oral cavity OAR. MATERIALS AND METHODS: Predictive models of severe acute mucositis were generated using radiotherapy dose to the oral cavity OAR or mucosal surface OAR and clinical data. Penalised logistic regression and random forest classification (RFC) models were generated for both OARs and compared. Internal validation was carried out with 100-iteration stratified shuffle split cross-validation, using multiple metrics to assess different aspects of model performance. Associations between treatment covariates and severe mucositis were explored using RFC feature importance. RESULTS: Penalised logistic regression and RFC models using the oral cavity OAR performed at least as well as the models using mucosal surface OAR. Associations between dose metrics and severe mucositis were similar between the mucosal surface and oral cavity models. The volumes of oral cavity or mucosal surface receiving intermediate and high doses were most strongly associated with severe mucositis. CONCLUSIONS: The simpler oral cavity OAR should be preferred over the mucosal surface OAR for NTCP modelling of severe mucositis. We recommend minimising the volume of mucosa receiving intermediate and high doses, where possible.

Isolation of a novel candidate oncogene within a frequently amplified region at 3q26 in ovarian cancer.

Amplification of 3q25-q26 was one of the most frequent chromosomal alterations in human ovarian carcinoma. A chromosome microdissection-hybrid selection method was applied to isolate transcribed sequences from a primary ovarian cancer containing high-copy-number amplification of 3q26 using 3q26 band-specific DNAs generated by chromosome microdissection. Using this method, we have isolated a novel candidate oncogene eIF-5A2 (eukaryotic initiation factor 5A2). eIF-5A2 shares 82% identity of amino acid sequence with eIF-5A including the minimum domain needed for eIF-5A maturation by hypusine modification at lysine-50 residue. Amplification and overexpression of eIF-5A2 was frequently detected in primary ovarian cancers and ovarian cancer cell lines. The proliferation-related function of eIF-5A supports that eIF-5A2 is a candidate oncogene related to the development of ovarian cancer.

Evidence of cisplatin-induced senescent-like growth arrest in nasopharyngeal carcinoma cells.

Cellular senescence is a programmed cell response leading to growth arrest in human diploid fibroblasts. We have shown that a nasopharyngeal carcinoma cell line, CNE1, following treatment by the DNA-damaging agent cisplatin, can undergo cellular senescent-like growth arrest, similar to fibroblasts, judged by cellular morphological changes and the expression of senescence-associated beta-galactosidase (SA-beta-gal). This senescent-like change was dose related; at 0.5 microgram/ml, the percentage of cisplatin-induced SA-beta-gal-positive cells was high (40-96%), and the staining was intense. Higher doses (1.0 and 2.0 micrograms/ml) of cisplatin induced lower SA-beta-gal expression (30-70%), and the process was irreversible. This cisplatin-induced cellular senescent-like response was not due to the inhibition of telomerase activity. Our results indicate that cellular senescent-like pathways exist in nasopharyngeal carcinoma cells and can be induced by cisplatin. Our evidence suggests that cellular senescent-like responses may be a cellular protection mechanism that acts differently in response to different degrees of cellular damage.

The association of chromosome 8p deletion and tumor metastasis in human hepatocellular carcinoma.

To understand the genetic mechanisms underlying the progression of hepatocellular carcinoma (HCC) metastasis, differences of genomic alterations between 10 pairs of primary HCC tumors and their matched metastatic lesions were analyzed by comparative genomic hybridization. Several chromosomal alterations including loss of 8p, 4q, 17p, and 19p, gain of 5p and high-level amplification of 1q12-q22 were detected in two or more cases. The most significant finding is the loss of 8p which was detected in 8 metastatic tumors but only in 3 corresponding primary tumors (P = 0.03). This result suggests that the deletion of chromosome 8p might contribute to the development of HCC metastasis. Another interesting result is the detection of a minimum high-level amplification region at 1q12-q22 in HCC. This result provides a candidate amplification region in HCC for further study to identify amplified oncogenes related to the development or progression of HCC. Finally, this study provides a practicable model to detect specific genetic alterations related to the tumor metastasis through comparing the primary tumor and its corresponding metastatic lesion using comparative genomic hybridization technique.

Multicenter phase II trial of mitoxantrone in patients with advanced nasopharyngeal carcinoma in Southeast Asia: an Asian-Oceanian Clinical Oncology Association Group study.

PURPOSE: Patients with advanced nasopharyngeal carcinoma (NPC) have a high incidence of recurrence and often develop distant metastases despite local control. This prospective multicenter phase II trial was conducted to evaluate the safety and efficacy of Novantrone (mitoxantrone; Lederle Laboratories, Wayne, NJ) in the therapy of patients with advanced NPC. PATIENTS AND METHODS: One hundred eight patients with advanced NPC, namely, those with recurrent or persistent disease following primary radiotherapy, or newly diagnosed metastatic disease, were treated with mitoxantrone. Mitoxantrone was administered intravenously at an initial dose of 12 mg/m2 and repeated every 3 weeks, with dose escalation to a maximum of 14 mg/m2. The distribution of histologic subtypes was representative of NPC, with the majority being (61%) undifferentiated (or anaplastic) carcinoma. RESULTS: The overall response rate (complete response [CR] and partial response [PR]) was 25% (95% confidence interval, 17% to 33%). The median response duration, time to treatment failure, and survival duration were 140, 82, and 394 days, respectively. Histology (poorly differentiated squamous cell) was found to be the only important factor in predicting response (P = .04) based on a multivariate analysis of nine pretreatment characteristics. The major dose-limiting toxicity was leukopenia. The incidences of nausea/vomiting, alopecia, and stomatitis/mucositis were 34%, 6%, and 3%, respectively. None were severe. Two patients had asymptomatic, moderate Alexander-grade cardiotoxicity. CONCLUSION: This study represents a large, controlled multicenter trial of single-agent mitoxantrone in the treatment of advanced NPC. Mitoxantrone was well tolerated and produced an overall response rate comparable to that of other single-agent therapies used in the treatment of advanced head and neck cancer. Combination trials with mitoxantrone for advanced disease should be considered.

Local control models of cardiac excitation-contraction coupling. A possible role for allosteric interactions between ryanodine receptors.

In cardiac muscle, release of activator calcium from the sarcoplasmic reticulum occurs by calcium- induced calcium release through ryanodine receptors (RyRs), which are clustered in a dense, regular, two-dimensional lattice array at the diad junction. We simulated numerically the stochastic dynamics of RyRs and L-type sarcolemmal calcium channels interacting via calcium nano-domains in the junctional cleft. Four putative RyR gating schemes based on single-channel measurements in lipid bilayers all failed to give stable excitation-contraction coupling, due either to insufficiently strong inactivation to terminate locally regenerative calcium-induced calcium release or insufficient cooperativity to discriminate against RyR activation by background calcium. If the ryanodine receptor was represented, instead, by a phenomenological four-state gating scheme, with channel opening resulting from simultaneous binding of two Ca2+ ions, and either calcium-dependent or activation-linked inactivation, the simulations gave a good semiquantitative accounting for the macroscopic features of excitation-contraction coupling. It was possible to restore stability to a model based on a bilayer-derived gating scheme, by introducing allosteric interactions between nearest-neighbor RyRs so as to stabilize the inactivated state and produce cooperativity among calcium binding sites on different RyRs. Such allosteric coupling between RyRs may be a function of the foot process and lattice array, explaining their conservation during evolution.

Elevation of plasma osteopontin level in patients with undifferentiated nasopharyngeal carcinoma.

AIMS: We evaluated the clinicopathologic relevance of plasma osteopontin (OPN) level in nasopharyngeal carcinoma patients. METHODS: Seventy-two plasma samples were collected from patients with undifferentiated nasopharyngeal carcinoma (NPC) before radiotherapy. Plasma OPN level was determined by quantitative sandwich enzyme immunoassay. The plasma OPN level was evaluated for its clinicopathologic relevance. RESULTS: The mean plasma OPN level was significantly higher in NPC patients than in normal controls (184.66 vs 75.89 ng/ml, p<0.001). In addition, high OPN level was found in the patients with advanced cancer and was correlated with neck node metastasis (p<0.05). CONCLUSIONS: Our findings indicated a potential role of OPN in the pathogenesis and nodal metastasis of undifferentiated NPC.

A phase II study of ifosfamide, 5-fluorouracil and leucovorin in patients with recurrent nasopharyngeal carcinoma previously treated with platinum chemotherapy.

The aim of this study was to evaluate the efficacy and toxicity of ifosfamide, 5-fluorouracil (5-FU) and leucovorin (IFL) as a second-line chemotherapy regimen in patients with recurrent undifferentiated nasopharyngeal carcinoma (NPC) previously treated with platinum/5-FU. Between June 1997 and February 1999, 18 patients were entered into the study. 3 patients had loco-regional recurrence, 12 had distant metastases and 3 had both loco-regional recurrence and distant metastases. All patients had previously received platinum/5-FU as adjuvant or palliative treatments. The IFL regimen consisting of ifosfamide 1.2 g/m(2) (with mesna), 5-FU 375 mg/m(2) and leucovorin 20 mg/m(2) for 5 days and was repeated every 21 days. The dose of ifosfamide was escalated to 1.4 and 1.6 g/m(2) in subsequent cycles according to the bone marrow toxicity, and the dose of 5-FU to 450 and 525 mg/m(2) according to the severity of mucositis. Patients received a median of 3 cycles of IFL (range: 2-6), with a median total ifosfamide dose of 21 g/m(2) (range: 13-46) and a median total 5-FU dose of 6.75 g/m(2) (range: 4.1-14.7). The median follow-up was 10 months (range: 4-25). 9 patients (50%) achieved a partial response and 1 patient (6%) achieved a complete response, with an overall response rate of 56% (95% confidence interval (CI): 32-80%). For those patients who responded to IFL, 8 had subsequent disease progression on follow-up, with a median response duration of 7.1 months (95% CI: 5.3-8.9). The median time to progression for all patients was 6.5 months (95% CI: 4.2-8.7). 12 patients are still alive with an estimated 1-year survival probability rate of 51%. Treatments were well tolerated, only 1 patient had grade 3 emesis. None of the patients had grade 3/4 anaemia, leucopenia or thrombocytopenia, although IFL was discontinued in 1 patient because of persisting thrombocytopenia. IFL is an effective second-line regimen in patients with recurrent NPC and is well tolerated with mild toxicity. Combining platinum and IFL in chemonaïve patients may further improve the overall response rate and duration and is worth investigating in future trials.

The effect of loco-regional control on distant metastatic dissemination in carcinoma of the nasopharynx: an analysis of 1301 patients.

PURPOSE: This study evaluated the effect of loco-regional control on incidence of distant metastases in patients with nasopharyngeal carcinoma. METHODS AND MATERIALS: Retrospective analysis was performed on 1301 patients with nasopharyngeal carcinoma treated from 1976-1989 in our hospital. The effect of different prognostic indicators on distant metastases free survival (DMFS) was analyzed, including T stage, N stage, sex, and loco-regional control. The significance of loco-regional control in distant metastatic dissemination was further studied with period and subgroup analysis. Cox regression was performed to identify the independent prognostic variables. RESULTS: Patients with loco-regional relapse had significantly higher distant metastases rate than patients with loco-regional control (time-adjusted distant metastases rate at 5 years was 40.7% vs. 29.4%, p = 0.0012). By period analysis, the effect of loco-regional control on distant metastases was found to be significant in the first 2 years from diagnosis. Subgroup analysis showed that loco-regional relapse was associated with significantly higher distant metastases rate in patients with T1, N0, and N1 disease (p = 0.001, 0.001, 0.0226, respectively). The Cox regression model also confirmed loco-regional control as an independent prognostic indicator of distant metastases (p = 0.0001) besides T stage (p = 0.0006) and N stage (p = 0.0001). CONCLUSION: Loco-regional relapse is a significant risk factor for development of distant metastases. Further effort should be made to improve loco-regional control and to eradicate distant metastases.

Nasopharyngeal carcinoma: orderly neck node spread.

A prospective study of 271 consecutive patients with newly diagnosed nasopharyngeal carcinoma was undertaken to assess the pattern of cervical nodal involvement with reference to 10 cervical nodal groups and three levels of neck; 204 (75.3%) patients were found to have cervical lymphadenopathy at presentation. Fifty-four (26.5%) of these patients had right cervical lymphadenopathy, 70 (34.3%) had left cervical lymphadenopathy, and 80 (39.2%) had bilateral cervical lymphadenopathy. The occurrence of lymphadenopathy in the 10 cervical nodal groups and the mean size of nodes in these nodal groups were computed. The subdigastric and upper jugular group was involved in more than 95% of cases. The lower the position in the neck, the less frequently the nodal group was involved. The mean size of nodes was largest in the subdigastric and upper jugular region compared with the other groups. The nodes in the upper neck were generally larger than those in the lower neck. The lower two levels of neck were involved without involvement of the upper level of the ipsilateral neck in fewer than 4% of cases. The present study indicates that neck node involvement by nasopharyngeal carcinoma is by orderly spread down the neck, which explains the adverse prognostic significance of neck node involvement in the lower neck. The orderly involvement of the neck nodes suggests that prophylactic irradiation of the neck should be given at least one level beyond the clinical extent of disease, which for patients with no clinically palpable node would mean prophylactic irradiation of the upper neck.

Treatment of stage I nasopharyngeal carcinoma: analysis of the patterns of relapse and the results of withholding elective neck irradiation.

This is a retrospective analysis of 196 patients with nasopharyngeal carcinoma Stage I (Ho's classification) treated by megavoltage radiation during 1980-1984. The primary target volume included all potential sites of local invasion and the first station lymph nodes at retropharyngeal spaces. Two different dose schedules were used, both gave a total tumor dose biologically equivalent to 65 Gy by conventional fractionation, and both achieved a 5-year actuarial local-recurrence-free survival of 88%. Elective neck irradiation was withheld in all except seven patients. The overall 7-year actuarial survival was 85%, but the relapse-free survival was only 62%. The patterns of relapse, prognostic factors, and treatment complications were analyzed. Eighteen patients (9%) recurred locally. Radical retreatment with radiation achieved complete remission in seven out of fifteen cases. Distant failure occurred in 17 patients (9%). Although 57 (30%) of the 189 patients without elective neck irradiation subsequently showed lymph node involvement, none of the seven regionally-treated patients relapsed. The successful regional salvage rate was 81% overall (46 out of 57 patients), but 90% (44 of 49) for those properly treated with whole neck irradiation. However, the 7-year actuarial survival was lower in patients with nodal relapse than those without (70% versus 87%) because of the associated higher incidence of hematogenous dissemination. The various aspects of treatment, the value of elective neck irradiation in particular, are discussed.

Transpalatal insertion of radioactive gold grain for the treatment of persistent and recurrent nasopharyngeal carcinoma.

PURPOSE: To evaluate the efficacy of radioactive gold grain implant via the split palate approach in the control of locally recurrent or persistent nasopharyngeal carcinoma. METHODS AND MATERIAL: Forty-three patients, 10 for persistent NPC, 28 for first relapse in the nasopharynx, and five for second relapse in the nasopharynx, were treated. The diameter of the tumors at the time of gold grain implant ranged from 0.5 to 5 cm, the number of gold grains inserted varied from 4 to 14, the median number was seven. RESULTS: There was no significant difference in the control of the primary tumor for persistent disease (80% at 5 years), first relapse (61% at 5 years) and second relapse (80% at 3 years), p = 0.8845. The difference in survival between the three subgroups of patients, however, was highly significant (p = 0.0040). Thirty patients had CT evaluation before gold grain implant and the tumor was found confined to the nasopharynx in 21, in the remaining nine patients erosion of the sphenoid sinus or other parts of the base of skull was noted. The difference in the control between those patients with tumors confined to the nasopharynx and those patients with extranasopharyngeal extension of tumor almost reached statistical significance (81% and 44% respectively at 5 years, p = 0.0554). For the six patients who developed local recurrence after gold grain implant and were evaluable for the pattern of failure, the recurrent tumors were considered originating from another region of the nasopharynx in four, and in-field failure in the other two cases. CONCLUSION: Radioactive gold grain implant as salvage treatment provides satisfactory control of persistent and recurrent nasopharyngeal carcinoma. The local control was better when the tumor was localized to the nasopharynx, thus underlines the importance of close follow-up for early recognition of relapse and persistent tumor. However, such patients still suffered from high incidence of regional and distant failure, the pathophysiology and management of which require further investigation.

Computed tomography evaluation of neck node metastases from nasopharyngeal carcinoma.

PURPOSE: To study the role of computed tomography in the pre-therapy evaluation of nasopharyngeal carcinoma. METHODS AND MATERIALS: The computed tomography of 119 new patients of nasopharyngeal carcinoma were evaluated independent of clinical findings for neck node metastases, and then compared with clinical findings. Contrast enhanced axial scans were obtained at 5 mm intervals with the infraorbitomeatal line parallel to the gantry. Scans were obtained from the supra-sellar cistern to the C5 or C6 vertebra for the evaluation of the base of skull, nasopharynx, paranasopharyngeal space and the upper and mid neck. RESULT: The present study confirmed the disparity of nodal extent documented by clinical palpation and computed tomography. Of the 37 patients who have no clinically palpable node (N0), computed tomography showed nodal involvement in 11 (29.7%) of them, and they were up-staged from N0 to N1. Computed tomography showed multiple or bilateral nodes in seven (58.3%) of the 12 patients with AJC N1 disease and they were hence up-staged to N2. All together, there were 28 (23.5%) patients who have no computed tomography evidence of nodal involvement by tumor. In agreement with clinical experience, the most commonly involved nodal groups were the upper internal jugular and upper spinoaccessary, followed by the lateral retropharyngeal. The percentage of nodes which were not clinically palpable was roughly the same for different regions (15-30%), except, as expected, that all the retropharyngeal nodes were not palpable. The risk of harboring retropharyngeal node was proportional to the size of the largest node in the ipsilateral neck. CONCLUSION: A significant proportion of patients with clinically negative neck (N0) or AJC N1 disease will be upstaged by computed tomography, thus supporting its routine use in pre-therapy evaluation of nasopharyngeal carcinoma.

Radiotherapy for nasopharyngeal carcinoma: shielding the pituitary may improve therapeutic ratio.

PURPOSE: Nasopharyngeal carcinoma (NPC) is well known for its invasiveness and erosion of the base of the skull is not uncommon. Before the advent of computed tomography, the evaluation of the base of the skull was by plain radiography. Because of the low sensitivity of these investigations, traditional teaching has included the sphenoid sinus in the volume of irradiation. Increase in longevity of patients allows the manifestation and documentation of the long-term sequelae of irradiating the hypothalamic-pituitary axis and the temporal lobes. This study is an attempt to evaluate whether the hypothalamic-pituitary axis can be shielded from the target volume in a proportion of NPC patients. METHODS AND MATERIALS: One hundred fifty-two NPC patients with no evidence of erosion of the base of the skull and sphenoid, nor extension to the nasal fossa and ethmoid sinuses were randomized to receive standard radiotherapy covering the whole sphenoid sinus or radiotherapy using a modified technique that shields the pituitary and the anterior part of the hypothalamus. This modified technique also shields a large part of the lower temporal lobes that are otherwise covered by standard treatment portals. The characteristics and treatment of the two subgroups of patients were otherwise comparable. RESULTS: At a median follow-up of 31.5 months, the tumor control between the two subgroups of patients were comparable (p = 0.3928). However, 8 of the 71 patients in the unshielded group had developed symptomatic neuroendocrine complications, while none of the other group did (p = 0.0061). Two patients developed secondary hypothyroidism, one patient developed oligomenorrhoea associated with raised prolactin, and five patients developed temporal lobe necrosis. CONCLUSIONS: The protective effect on neuroendocrine complication of this shield was demonstrated at median follow-up of 31.5 months, and the local control was not jeopardized. Modification of treatment technique as presently described, which is applicable to one-third of NPC patients to improve the therapeutic ratio, is recommended for general use.