A prospective study of clinical characteristics and outcomes of acute kidney injury in a tertiary care Centre.

BACKGROUND: Acute kidney injury (AKI) is a major global health problem. We aim to evaluate the epidemiology, risk factors and outcomes of AKI episodes in our single centre. METHODOLOGY: We prospectively identified 422 AKI and acute on chronic kidney disease episodes in 404 patients meeting KDIGO definitions using electronic medical records and clinical data from 15th July to 22nd October 2016, excluding patients with baseline estimated GFR (eGFR) of < 15 mL/min. Patients were followed up till 6 months after AKI diagnosis. RESULTS: The mean age was 65.8 ± 14.1. Majority of patients were male (58.2%) of Chinese ethnicity (68.8%). One hundred and thirty-two patients (32.6%) were diagnosed in acute care units. Seventy-five percent of patients developed AKI during admission in a non-Renal specialty. Mean baseline eGFR was 50.2 ± 27.7 mL/min. Mean creatinine at AKI diagnosis was 297 ± 161 µmol/L. Renal consultations were initiated at KDIGO Stages 1, 2 and 3 in 58.9, 24.5 and 16.6% of patients, respectively. Three hundred and ten (76.7%) patients had a single etiology of AKI with the 3 most common etiologies of AKI being pre-renal (27.7%), sepsis-associated (25.5%) and ischemic acute tubular necrosis (15.3%). One hundred and nine (27%) patients received acute renal replacement therapy. In-hospital mortality was 20.3%. Six-month mortality post-AKI event was 9.4%. On survival analysis, patients with KDIGO Stage 3 AKI had significantly shorter survival than other stages. CONCLUSION: AKI is associated with significant in-hospital to 6-month mortality. This signifies the pressing need for AKI prevention, early detection and intervention in mitigating reversible risk factors in order to optimize clinical outcomes.

A unique presentation of acute liver failure from herpes simplex virus hepatitis.

We present the case of a patient, with history of myelodysplastic syndrome and recent bone marrow transplant, who developed fulminant liver failure secondary to herpes simplex virus (HSV) hepatitis. His presentation was unique, as findings of liver microabscesses on computed tomography scan have not been described previously in this patient population. Despite initial treatment with acyclovir, he continued to deteriorate, and later sensitivities found the HSV strain to be resistant to acyclovir. HSV hepatitis with secondary liver failure is rare and, without appropriate treatment, its mortality is >80%. Early suspicion and immediate therapy are the keys to improve patient survival.

Primary intracerebral Hodgkin lymphoma with recurrence.

OBJECTIVE: To report a case of primary intracerebral Hodgkin lymphoma with disease recurrence. METHODS: Case report and review of the literature. RESULTS: A 58-year-old immunocompetent male presented with aphasia. Neuroimaging revealed a left temporal lobe lesion. A craniotomy and resection were performed, and the diagnosis of classical Hodgkin lymphoma was made. Systemic work-up for lymphoma was negative. Postoperatively, the patient was treated with whole brain irradiation. 14 months later, the patient developed an enhancing lesion in his pons and received combination chemotherapy and radiation therapy. Repeat imaging demonstrated leptomeningeal enhancement and multiple lesions throughout the cerebral hemispheres, cerebellum and brainstem. COMMENT: We report what appears to be the first case of a patient with aggressive primary intracerebral Hodgkin lymphoma with disease recurrence.

Functional polymorphisms in the BRCA1 promoter influence transcription and are associated with decreased risk for breast cancer in Chinese women.

BACKGROUND: The BRCA1 gene is an important breast-cancer susceptibility gene. Promoter polymorphisms can alter the binding affinity of transcription factors, changing transcriptional activity and may affect susceptibility to disease. METHODS AND RESULTS: Using direct sequencing of the BRCA1 promoter region, we identified four polymorphisms c.-2804T-->C (rs799908:T-->C), c.-2265C-->T (rs11655505:C-->T), c.-2004A-->G (rs799906:A-->G) and c.-1896(ACA)(1)-->(ACA)(2) (rs8176071:(ACA)(1)-->(ACA)(2)) present in Hong Kong Chinese. Each polymorphism was studied independently and in combination by functional assays. Although all four variants significantly altered promoter activity, the c.-2265T allele had stronger binding than the C allele, and the most common mutant haplotype, which contains the c.-2265T allele, increased promoter activity by 70%. Risk association first tested in Hong Kong Chinese women with breast cancer and age-matched controls and replicated in a large population-based study of Shanghai Chinese, together totalling >3000 participants, showed that carriers of the c.-2265T allele had a reduced risk for breast cancer (combined odd ratio (OR) = 0.80, 95% CI 0.69 to 0.93; p = 0.003) which was more evident among women aged >or=45 years at first diagnosis of breast cancer and without a family history of breast cancer (combined OR = 0.75, 95% CI 0.61 to 0.91; p = 0.004). The most common haplotype containing the c.-2265T allele also showed significant risk association for women aged >or=45 years without a family history of breast cancer (OR = 0.64, 95% CI 0.46 to 0.89; p = 0.008). CONCLUSION: This comprehensive study of BRCA1 promoter polymorphisms found four variants that altered promoter activity and with the most significant contribution from c.-2265C-->T, which could affect susceptibility to breast cancer in the Chinese population. Its significance in other populations remains to be investigated.

Family history? The forgotten question in high-risk colorectal cancer patients.

AIM: The aim of the study was to investigate the frequency and detail of family history recorded for patients diagnosed with potentially high-risk colorectal cancer, and to determine the proportion of these patients referred to a high-risk assessment clinic. METHOD: Medical records of patients diagnosed with colorectal cancer under the age of 50 admitted to a major Sydney teaching hospital were reviewed. The proportion of records containing information about family history was calculated. Associations between recording of family history and demographic and clinical characteristics of patients were investigated. Logistic regression modelling was performed to identify significant, independent predictors of study outcomes. RESULTS: Of 113 patients with colorectal cancer diagnosed under the age of 50 years, 61 (54%, 95% CI: 44-63%) had an entry in their hospital medical record about family history. Family history was significantly less likely to be recorded for females, for those admitted via the Emergency Department, and for those with shorter lengths of stay. A significant family history was found in 51% of the 61 patients who had a family history recorded. Records of patients attending specialist colorectal surgeons were significantly more likely to contain information about family history than those who attended other specialists (P = 0.04). Only 14 patients (12%, 95% CI: 7-20%) were formally referred for further genetic assessment. CONCLUSION: These results suggest that family history is still being neglected in routine clinical practice, and high-risk assessment services are underutilized, implying the need for further dissemination of guidelines with regard to the recognition and management of hereditary colorectal cancer.

The physical state of human papillomavirus type 16 DNA in cervical carcinomas of Hong Kong Chinese.

The presence of human papillomavirus (HPV) in 15 cervical carcinoma specimens obtained from Hong Kong Chinese patients was analyzed by Southern blot hybridization studies. In nine (60%) of them, HPV 16 genomes were detected, while two others (13.3%) were found to harbor HPV DNA of unknown type closely related to HPV 16. All of them were classified as squamous cell carcinomas according to WHO guidelines. In addition, the presence of HPV 18 was shown in another two (13.3%) squamous cell carcinoma samples. Among the nine tumors harboring HPV 16, four specimens (44.4%) have HPV in integrated forms, while four others (44.4%) have HPV in episomal forms. The simultaneous presence of both episomal and integrated forms was demonstrated in the remaining tissue sample (11.2%). The result obtained here indicates a strong association between HPV infection and cervical carcinogenesis in Hong Kong Chinese, with HPV 16 prevalent in squamous cell carcinoma. Moreover, the persistence of HPV 16 episomes in some of the tumor specimens suggests that extrachromosomal HPV DNA, possibly acting synergistically with other oncogenic factors, is also capable of inducing cervical cancer.

Primary non-Hodgkin's lymphoma of the nose and nasopharynx: clinical features, tumor immunophenotype, and treatment outcome in 113 patients.

PURPOSE: To study the clinical features and outcome for primary non-Hodgkin's lymphomas of the nose/nasopharynx (NNP-NHLs) according to immunophenotype. PATIENTS AND METHODS: One hundred thirteen Chinese patients with primary NNP-NHLs that belonged to the categories E, F, G, or H according to the Working Formulation (WF), with full immunophenotypic data and complete clinical follow-up data, were analyzed in this retrospective study. RESULTS: Ninety (79.6%) patients had localized (stage I or II) disease, while 23 (20.4%) had stage III or IV disease. The lymphomas in 51 (45.1%), 24 (21.3%), and 38 (33.6%) patients showed natural killer (NK)/T- (CD56-positive), T-cell, and B-cell immunophenotype, respectively. Seventy-three patients (65.8%) achieved a complete remission, of whom 34 (46.6%) subsequently relapsed. The median follow-up time for those alive was 88 months. The 5-year actuarial disease-free and overall survival rates were 34.4% and 37.9%, respectively. Multivariate analysis showed that only stage and immunophenotype were significant for survival. NK/T lymphomas were distinctive among the three immunophenotypes in the following aspects: the highest male-to-female ratio, more frequent involvement of the nasal cavity alone, higher risk of dissemination to the skin, more frequent development of hemophagocytic syndrome, and the worst prognosis (overall median survival, 12.5 months). CONCLUSION: The three immunophenotypes studied are shown to exhibit different clinical patterns. Since the NK/T phenotype carries the worst prognosis, patients who present with NNP-NHL should have their tumors analyzed for CD56 expression.

In-depth evaluation of the AJCC/UICC 1997 staging system of nasopharyngeal carcinoma: prognostic homogeneity and proposed refinements.

PURPOSE: To critically evaluate the American Joint Commission on Cancer (AJCC)/International Union Against Cancer (UICC) 1997 staging system and look back on its achievements by comparing it with the AJCC/UICC 1992 and Ho 1978 staging systems. To identify areas for additional refinement, we analyzed the prognostic heterogeneity within each stage in depth, which provided important clues for the addition or better categorization of the different defining criteria. METHODS AND MATERIALS: We performed a retrospective review of the data from 1294 consecutive biopsy-proven nonmetastatic nasopharyngeal carcinoma patients and staged the extent of disease according to the defining criteria of the three staging systems. All patients had undergone detailed pretreatment assessment by fiberoptic endoscopy and CT. Radical-intent radiotherapy was given using the Ho technique according to our standard protocol. RESULTS: The AJCC/UICC 1997 staging system was superior to the other two staging systems, because it assigned patients to more uniform-size stage groupings and correlated better with prognosis. Parapharyngeal space involvement was not an independent predictor for survival, local control, or metastasis. On the other hand, carotid space involvement correlated with a greater likelihood of metastasis. Prognostic heterogeneity was found. Those with orbit, cranial nerve, or intracranial involvement fared worse within Stage T4; those with a maximal lymph node size >3 cm fared worse within Stage N2; and those with bilateral lymph node metastasis fared worse within Stage N3. CONCLUSION: The prognostic accuracy of the AJCC/UICC 1997 staging system can be improved further by recategorization of the T, N, and group stage criteria.

Retrospective analysis of patients with nasopharyngeal carcinoma treated during 1976-1985: survival after local recurrence.

PURPOSE: To study the value of re-irradiation, the overall survival and pattern of failures for patients with nasopharyngeal recurrence. METHODS AND MATERIALS: All the 891 patients with local recurrence following radiotherapy for nasopharyngeal carcinoma during 1976-1981 were retrospectively analyzed. Only 70% of them had local failure alone at the time of detection, and the T-stage distribution (by Ho's system) was 31% rT1, 16% rT2, 51% rT3, and 1% rT?. Seven hundred and six (79%) patients had been re-irradiated with various techniques and doses. Among those who failed, 50 had further irradiation. RESULTS: The overall 5- and 10-year actuarial cancer-specific survival rates were 14% and 9%, respectively. Patients with rT3 disease had the worst prognosis. Successful local salvage was achieved in 32% of those re-irradiated (26% of the whole series). The highest control rate was achieved by those treated with external radiotherapy to 60 Gy (equivalent) or above. Only 8/50 patients responded to the third course of radiotherapy. The cumulative incidence of late post-re-irradiation sequelae was 24%, and the treatment mortality rate 1.8%. Besides local failure, 54% had regional relapse and/or distant metastasis. Thus, only 16% of recurrent patients were totally disease-free at final assessment. CONCLUSION: The overall prognosis for patients with nasopharyngeal recurrence was grave. High dose re-irradiation could achieve successful local salvage in a substantial number of patients with early recurrence, but late complications did occur. Furthermore, high incidence of failure at other sites was observed.

Retrospective analysis of 5037 patients with nasopharyngeal carcinoma treated during 1976-1985: overall survival and patterns of failure.

This is a retrospective analysis of 5037 patients with squamous cell carcinoma of the nasopharynx treated during the years 1976-1985. The stage distribution according to Ho's classification was 9% Stage I, 13% II, 50% III, 22% IV, and 6% Stage V. Only 4488 (89%) patients had a full course of megavoltage radiation therapy. The median equivalent dose to the nasopharyngeal region was 65 Gy and cervical region in node-positive patients 53 Gy. Seventy percent (906/1290) of the node-negative patients had no prophylactic neck irradiation. The overall actuarial 10-year survival rate was 43%, and the corresponding failure-free survival 34%. Altogether, 4157 (83%) patients achieved complete remission lasting more than 6 months, but 53% (2205/4157) of them relapsed after a median interval of 1.4 years. The 10-year actuarial local, regional, and distant failure-free rates were 61%, 64%, and 59%, respectively. Thirty-eight percent (338/891) of all patients with local recurrence achieved second local remission. The local complete remission rate with aggressive re-irradiation alone was 47% (333/706). But 37% (124/338) of the responders recurred the second time. The incidence of distant failure correlated significantly with both the N-stage and the T-stage, with the highest (57%) occurring in patients with N3 disease. The incidence of nodal relapse in node-negative patients was 11% (44/384) among those given prophylactic neck irradiation, but 40% (362/906) among those without. Therapeutic irradiation achieved a complete regional remission rate of 90% (306/339). However, despite successful salvage, these patients had a significantly higher distant failure rate than those without nodal relapse, even if they remained local-failure-free (21% vs 6%). Patients treated during 1981-1985 achieved significantly better treatment results than those treated during 1976-1980, especially in terms of the overall survival (57% vs 47% at 5-year), the overall failure-free survival (42% vs 35% at 5-year), and the local failure-free rate (70% vs 63% at 5-year). The possible contributing factors are discussed.

Reirradiation for recurrent nasopharyngeal carcinoma: factors affecting the therapeutic ratio and ways for improvement.

PURPOSE: To identify factors for maximizing local salvage and minimizing damages by reirradiation for recurrent nasopharyngeal carcinoma. METHODS AND MATERIALS: 654 patients with recurrent nasopharyngeal carcinoma treated by reirradiation during 1976-1992 were retrospectively analyzed. Various fractionation schedules had been used during primary treatment with the total dose ranging from 45.6-70 Gy, fractional dose (at different phases) 1.5-4.2 Gy, and overall time 36-101 days. The gap between the two courses ranged from 0.5-10.6 years. Eighty-two percent of patients were reirradiated with teletherapy, 6% brachytherapy, and 12% with both. For those treated with teletherapy alone, the total dose ranged from 7.5-70 Gy, fractional dose 1.8-5 Gy, and overall time 3-89 days. RESULTS: The 5-year actuarial local salvage and complication-free rates were 23% and 52%, respectively. Multivariate analyses showed that the extensiveness of local recurrence was the most significant factor affecting local salvage, while T-stage of primary tumor also influenced prognosis. Choice of method for reirradiation and fractional effect during both courses affected the risk of late complications. For patients treated by teletherapy alone, the hazard of local failure decreased by 1.7% per Biological Effective Dose (assuming alpha/beta ratio = 10) of the second course, while radiation factors during primary radiotherapy had no significant effect. On the other hand, the risk of late complications was predominantly affected by the primary treatment: the hazard increased by 4.2% per Biological Effective Dose (assuming alpha/beta ratio = 3) of the first course, while the corresponding impact of reirradiation failed to reach statistical significance. Length of the gap between the two courses did not affect the outcome. CONCLUSION: Early detection of local recurrence and adequate total dose by reirradiation are crucial for improving the chance of local salvage. Combination of teletherapy and brachytherapy should be considered whenever feasible and large fractional dose avoided to minimize late complications. Optimization of biological dose during primary treatment is important.

Total biological effect on late reactive tissues following reirradiation for recurrent nasopharyngeal carcinoma.

PURPOSE: To assess the additional damage of normal tissues attributable to reirradiation and the magnitude of partial recovery following the initial course. METHODS AND MATERIALS: Symptomatic late complication rates (excluding xerostomia) in 3635 patients receiving one course (Group 1) and 487 patients receiving two courses of external radiotherapy (Group 2) for nasopharyngeal carcinoma were retrospectively analyzed and compared. RESULTS: Group 2 had significantly lower actuarial complication-free survival rates than Group 1: 48% versus 81% at 5 years. The post-retreatment incidence was significantly affected by biologically effective dose (BED) (assuming an alpha/beta ratio of 3 Gy) of the first course: hazard ratio (HR) = 1.04 per Gy(3) (p = 0.01), but only marginally by that of the second course: HR = 1.01 per Gy(3) (p = 0.06). If the summated BED was taken as the dose unit, it was estimated that a total BED of 143 Gy(3) would induce a 20% incidence at 5 years, while the corresponding dose projected from Group 1 was 111 Gy(3). The gap effect was insignificant in the overall analyses, but a trend of decreasing risk with increasing interval was observed in patients with gap > or = 2 years: HR = 0.86 per year (p = 0.07). CONCLUSION: The major determinant of post-retreatment complication is the severity of damage during the initial course. The sum of total doses tolerated is higher than that expected with a single-course treatment, suggesting occurrence of partial recovery (particularly in those reirradiated after an interval of 2 years or more).

T1 nasopharyngeal carcinoma: the effect of waiting time on tumor control.

PURPOSE: To study the effect of unperturbed tumor growth on the control of nasopharyngeal carcinoma. METHODS AND MATERIALS: This is a retrospective analysis of 290 patients with T1N0-3M0 disease (Ho's classification) treated by the same technique and dose schedule to the nasopharyngeal region. The median interval from diagnosis to commencement of irradiation was 26 days (range: 8-68 days). Cox proportional hazards analyses were performed to study the independent effect of waiting time on the probability of failure at various sites. Actuarial failure-free survival of patients with delay < 22 days, 22-28 days and > 28 days were also compared to illustrate the clinical observation. RESULTS: Both tests showed that waiting time had no significant impact on local failure: The N-stage stratified hazard ratio was 0.985 per day, and the 10-year local failure-free survival for the three groups was 76%, 80%, and 82%, respectively. A similar result was obtained for nodal control in patients with our scheduled neck irradiation. Although the p value of all tests failed to reach statistical significance, the N-stage stratified hazard ratio for distant failure was 1.020 per day, and the corresponding metastasis-free survival in patients with N2-3 disease was 70%, 65%, and 52%, respectively. For node-negative patients without elective neck irradiation, the hazard ratio was 1.019 per day, with the corresponding regional failure-free rates at 57%, 62%, and 33%, respectively. CONCLUSION: Delay in initiation of treatment to the primary target (within the range observed) did not affect the control rate at irradiated sites, but there was a trend (though statistically insignificant) towards increase in failures at untreated sites that were clinically too serious to be ignored.

Recurrent nasopharyngeal carcinoma: the puzzles of long latency.

PURPOSE: To study the peculiar characteristics of relapses with long latency following radical treatment for nasopharyngeal carcinoma. METHODS AND MATERIALS: 847 patients with nasopharyngeal recurrence were retrospectively studied, focusing on the independent effects of latency on different outcome aspects and its relationship with other prognostic factors. RESULTS: The proportion of recurrence with latency <2 years (Group A), 2-<5 years (Group B), and 25 years (Group C) were 52%, 39%, and 9%, respectively. A higher proportion of Group C originated from patients with node-negative early primary, but fewer of them were still confined within the nasopharynx at detection of recurrence. There was no significant difference in the choice of salvage modality, but among those reirradiated, more of Group C were treated with external beams to a higher dose. The difference in local salvage rate was not statistically significant, but the 5-year distant failure-free rates of the 3 groups were 57%, 67%, and 83%, respectively; and the corresponding disease-specific survival (DSS) were 14%, 20%, and 35%. Multivariate analysis confirmed the independent significance of latency in predicting distant failure (hazard ratio = 0.81 per year, p < 0.01) and cancer deaths (hazard ratio = 0.90 per year, p < 0.01). CONCLUSIONS: Nasopharyngeal recurrence with long latency showed different natural behavior: the prognosis was significantly better due to lower risk of distant failure.

Effect of time, dose, and fractionation on temporal lobe necrosis following radiotherapy for nasopharyngeal carcinoma.

PURPOSE: To study the relative effects of different radiation factors on temporal lobe necrosis (TLN) and predictive accuracy of different biological equivalent models. METHODS AND MATERIALS: Consecutive patients (1008) treated radically with four different fractionation schedules during 1976-1985 for T1 nasopharyngeal carcinoma were retrospectively analyzed. All were irradiated by megavoltage photons using the same technique. Their age ranged from 18-84 years, and 92% of patients had complete follow-up. The fractional dose to inferomedial parts of both temporal lobes ranged from 2.5-4.2 Gy, total dose 45.6-60 Gy, and overall time 38-75 days. RESULTS: Despite a lower total dose of 50.4 Gy, the 621 patients irradiated with 4.2 Gy per fraction had a significantly higher incidence of temporal lobe necrosis than the 320 patients treated to 60 Gy with 2.5 Gy per fraction: the 10-year actuarial incidence being 18.6% vs. 4.6%, p < 0.001. Multivariate survival analysis showed that fractional effect (product of total dose and fractional dose) was the most significant factor: p = 0.0022, hazard ratio (HR) = 1.044 per Gy2. Overall time and age were both insignificant. The alpha/beta ratio calculated from our data was 2.9 Gy (95% CI: -1.8, 7.6 Gy). Biological effective dose (BED(Gy3)), neuret, and brain tolerance unit all showed strongly significant correlation with the necrotic rate (p < 0.001), and gave similar predictions. The hazard of TLN increased by 14% per Gy3, and it was estimated that 64 Gy (at conventional fractionation of 2 Gy daily) would lead to a 5% necrotic rate at 10 years. Not only did the nominal standard dose (NSD) show the lowest value in terms of log likelihood and standardized HR, but its predictions on TLN deviated markedly from clinically observed rates. CONCLUSION: Fractional effect is the most significant factor affecting cerebral necrosis, and overall time has little protective effect. The BED formula, assuming an alpha/beta ratio of 3 Gy, is an appropriate model for predicting late effects on the temporal lobe, and NSD could give seriously misleading predictions.

Effect of time, dose and fractionation on local control of nasopharyngeal carcinoma.

To study the effect of radiation factors on local control of nasopharyngeal carcinoma, 1008 patients with similarly staged T1N03M0 disease (Ho's classification) were retrospectively analyzed. All patients were treated by megavoltage irradiation alone using the same technique. Four different fractionation schedules had been used sequentially during 1976-1985: with total dose ranging from 45.6 to 60 Gy and fractional dose from 2.5 to 4.2 Gy. The median overall time was 39 days (range = 38-75 days). Both for the whole series and 763 patients with nodal control, total dose was the most important radiation factor. The hazard of local failure decreased by 9% per additional Gy (p < 0.01). Biological equivalents expressed in terms of Biologically Effective Dose or Nominal Standard Dose also showed strong correlation. Fractional dose had no significant impact. The effect of overall treatment time was insignificant for the whole series, but almost reached statistical significance for those with nodal control (p = 0.06). Further study is required for elucidation, as 85% of patients completed treatment within a very narrow range (38-42 days), and the possible hazard is clinically too significant to be ignored.

Cavitation phenomena in mechanical heart valves: the role of squeeze flow velocity and contact area on cavitation initiation between two impinging rods.

In this study, the closing dynamics of two impinging rods were experimentally analyzed to simulate the cavitation phenomena associated with mechanical heart valve closure. The purpose of this study was to investigate the cavitation phenomena with respect to squeeze flow between two impinging surfaces and the parameter that influences cavitation inception. High-speed flow imaging was employed to visualize and identify regions of cavitation. The images obtained favored squeeze flow as an important mechanism in cavitation inception. A correlation study of the effects of impact velocities, contact areas and squeeze flow velocity on cavitation inception showed that increasing impact velocities results in an increase in the risk of cavitation. It was also shown that for similar impact velocities, regions near the point of impact were found to cavitate later for those with smaller contact areas. It was found that the decrease in contact areas and squeeze flow velocities would delay the onset and reduce the intensity of cavitation. It is also interesting to note that the squeeze flow velocity alone does not provide an indication if cavitation inception will occur. This is corroborated by the wide range of published critical squeeze flow velocity required for cavitation inception. It should be noted that the temporal acceleration of fluid, often neglected in the literature, can also play an important role on cavitation inception for unsteady flow phenomenon. This is especially true in mechanical heart valves, where for the same leaflet closing velocity, valves with a seat stop were observed to cavitate earlier. Based on these results, important inferences may be made to the design of mechanical heart valves with regards to cavitation inception.

Nasopharyngeal carcinoma: local control by megavoltage irradiation.

This is a retrospective analysis of the long-term local control in 4128 patients with non-disseminated nasopharyngeal carcinoma treated solely by megavoltage irradiation during the years 1976-1985. The T-stage distribution according to Ho's classification was T1 37%, T2 14% and T3 49%. Different fractionation schedules had been employed at different periods, and the median dose to the primary target was equivalent to 65 Gy by time dose fractionation calculation. In 8% (344) of patients the tumour failed to regress completely after the basic course, but 89% (148/167) of those suitable for salvage with additional irradiation eventually attained complete local remission. The cumulative incidence of local failure was 24% (5% persistence, 19% recurrence). The 10-year actuarial local failure-free survival was 67%. While patients with T2 and T3a tumours achieved local control comparable to T1, those with T3c-d had the poorest control (with highest incidence of persistence and advanced recurrence). T-stage adjusted analyses suggested a significant trend of dose-response: the odds ratios for local failure were 1.16 and 1.86, respectively, when patients given 60-63 Gy and 55-59 Gy were compared with those given 64 Gy or above (p value = 0.0018). Patients treated during 1981-1985 achieved higher local failure-free survival than those treated during 1976-1980 (75% versus 70% at 5 years, p value = 0.0013). The possible attributes are studied, and ways for future optimization of treatment discussed.