Quality of life in patients of nasopharyngeal carcinoma: validation of the Taiwan Chinese version of the EORTC QLQ-C30 and the EORTC QLQ-H&N35.

The authors followed the guidelines of translation and pilot testing of the EORTC QLQ-C30 and EORTC-QLQ-H&N35 questionnaires. The questionnaires were given to 50 nasopharyngeal carcinoma patients under active treatment and 50 under follow-up at our institution from November 2000 to June 2001. A retest was conducted 2 weeks after the first interview/form completion for the follow-up group. The intraclass correlation coefficients of the two questionnaires were moderate to high in the follow-up group. Cronbach's alpha coefficients of all scales of the two questionnaires were > or = 0.70 except that of cognitive functioning. Correlation of scales measuring similar dimensions of the QLQ-C30 and the SF-36 were moderate to high, while that of the QLQ-H&N35 and the QLQ-C30 and the SF-36 were moderate to low. Patients in the active treatment group had more serious acute problems due to disease and chemotherapy. Patients in the follow-up group had more serious chronic problems due to radiation therapy. We concluded that the Taiwan Chinese version of the EORTC QLQ-C30 and the EORTC QLQ-H&N35 had moderate to high test-retest reliability, high internal consistency in most scales, and could show the expected differences between patients in active treatment and follow-up group.

Cutaneous protothecosis: report of five cases.

Prototheca, a genus of achlorophyllic algae, is a rare cause of opportunistic infection in humans. About 80 human cases, mostly cutaneous infection caused by P. wickerhamii, have been reported world-wide. We describe the clinicopathological findings and treatments of five cases diagnosed in our department during the period 1991-97. The patients, including four elderly farmers, presented with pyoderma-like lesions or infiltrating papules and plaques on the extensor side of the extremities or face. All patients were immunocompromised, mostly due to systemic or topical steroids. The diagnosis was made in each case by finding typical endospores with morula-like structures in skin biopsy specimens. P. wickerhamii was isolated in four cases in which pretreatment culture of skin tissue was done. Except for one patient who died of asthma, the infection was cured after 2-7 weeks of amphotericin B, ketoconazole, itraconazole or fluconazole. Our cases illustrate that cutaneous protothecosis commonly manifested non-tender, pyoderma-like or infiltrating lesions and should be considered in the differential diagnosis of deep fungal or mycobacterial infection. This rare infection seemed more frequent in our region, possibly due in part to common steroid abuse among old people in Taiwan and there was a large population of elderly farmers in our area.

Induction chemotherapy with mitomycin, epirubicin, cisplatin, fluorouracil, and leucovorin followed by radiotherapy in the treatment of locoregionally advanced nasopharyngeal carcinoma.

PURPOSE: Survival in advanced nasopharyngeal carcinoma (NPC) is compromised by distant metastasis. Because mitomycin is active against hypoxic and G0 cells, which may help to eradicate micrometastasis, we investigated the effect of mitomycin-containing cisplatin-based induction chemotherapy. PATIENTS AND METHODS: Recruited for this study were American Joint Committee on Cancer (AJCC) 1992 staging system stage IV NPC patients with the following adverse features: obvious intracranial invasion, supraclavicular or bilateral neck lymph node metastasis, large neck node (> 6 cm), or elevated serum lactate dehydrogenase (LDH) level. Patients were given three cycles of chemotherapy before radiotherapy. The chemotherapy comprised a 3-week cycle of mitomycin, epirubicin, and cisplatin on day 1 and fluorouracil and leucovorin on day 8 (MEPFL). RESULTS: From January 1994 to December 1997, 111 patients were recruited. The median follow-up period was 43 months. The actuarial 5-year overall survival rate was 70% (95% confidence interval [CI], 60% to 80%; n = 111). For patients having completed radiotherapy (n = 100), the 5-year locoregional control rate was 70% (95% CI, 55% to 84%) and the distant metastasis-free rate was 81% (95% CI, 73% to 89%). The 5-year distant metastasis-free rate of N3a and N3b disease of AJCC 1997 staging system were 79% (95% CI, 62% to 95%) and 74% (95% CI, 60% to 89%), respectively. By Cox multivariate analysis, high pretreatment serum LDH level (P = .04) and neck nodal enlargement before radiotherapy (P = .001) were adverse prognostic factors of survival. CONCLUSION: The good 5-year survival of N3 disease supports the effectiveness of induction MEPFL in the primary treatment of advanced NPC. Further investigation to incorporate concurrent chemoradiotherapy is warranted.

Occupational exposure to wood, formaldehyde, and solvents and risk of nasopharyngeal carcinoma.

Our objective was to evaluate the link between occupational exposures to wood dust, formaldehyde, and solvents and the development of nasopharyngeal carcinoma (NPC). A case-control study was conducted among 375 newly diagnosed cases of NPC in Taipei, Taiwan, and 325 community controls matched to cases on sex, age, and geographical residence (99 and 87% response rates, respectively). Most cases (>90%) were diagnosed with WHO Types 2 or 3 (nonkeratinizing and undifferentiated carcinomas), whereas the remaining cases were diagnosed with WHO Type 1 (squamous cell carcinomas). A complete occupational history was obtained via a personal interview and blindly assessed by an industrial hygienist for intensity and probability of exposure to wood dust, formaldehyde, and solvents. Information on socio-demographic characteristics, cigarette smoking, dietary consumption of nitrosamines, and other potential confounding factors was obtained via a personal interview. Blood specimens were tested for human leukocyte antigen class I/II genotypes, polymorphisms in cytochrome P450 2E1 genotype, and various anti-EBV antibodies known to be associated with NPC. Analysis was performed using logistic regression; relative risk (RR) estimates and 95% confidence intervals (CI) were calculated. Individuals exposed to wood dust had an adjusted RR of 1.7 (95% CI = 1.0-3.0). Those exposed to wood dust for >10 years had an adjusted RR of 2.4 (95% CI = 1.1-5.0; p(trend) = 0.02). Risk was strongest for those first exposed before the age of 25 years and those seropositive to EBV. Individuals exposed to formaldehyde were at a more modest and nonsignificant increased risk of NPC (RR = 1.4; 95% CI = 0.93-2.2). Those exposed to formaldehyde for >10 years had an adjusted RR of 1.6 (95% CI = 0.91-2.9). The association between formaldehyde and NPC was stronger in analyses restricted to EBV seropositive individuals (RR = 2.7; 95% CI = 1.2-5.9). However, no dose response was observed with increasing duration or cumulative use. No association was observed between solvent exposure and NPC (RR = 1.2; 95% CI = 0.86-1.7). Occupational exposure to wood dust is likely to be involved in the development of NPC, a finding that is consistent with the known link between wood exposure and nasal adenocarcinomas. Formaldehyde exposure is less clearly linked to NPC, whereas exposure to solvents is unlikely to be involved in NPC pathogenesis.

Clinical characteristics of tricho-rhino-phalangeal syndrome type I in Taiwanese.

Tricho-rhino-phalangeal syndrome type I (TRPS-I) is a malformation syndrome characterized by distinctive craniofacial and skeletal abnormalities. Only one case of TRPS-I has been previously reported in Taiwan. This retrospective study analyzed the clinical, roentgenographic, and histopathologic findings in seven patients with a diagnosis of TRPS-I who were treated at a hospital in Tainan during a 6-year period from 1994 to 1999. Physical examination revealed fine, sparse, and short scalp hair, a pear-shaped nose, long philtrum, thinning of the lateral portion of the eyebrows, and brachydactyly of the thumbs and big toes. The stature and intelligence of these patients were normal. Histopathologic examination of the scalp in two patients showed hypotrichosis without inflammation or scarring. Roentgenographic evaluation of both hands and feet showed cone-shaped proximal epiphyses of the middle phalanges in all patients. The findings of this report suggest that TRPS-I is not rare among Taiwanese, although the island-wide incidence is not known. The diagnosis of this syndrome in our department was greatly facilitated by our prior experience with treatment of the first patient in this series because TRPS-I is readily recognizable by its characteristic clinical and roentgenographic features. The identification of these features is important to the facilitation of genetic and cosmetic counseling. In addition to the typical craniofacial manifestations, all patients in this study showed brachydactyly of the big toes. This additional feature appears to offer an easy way to recognize the syndrome clinically.

Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions.

Curcumin (diferuloylmethane), a yellow substance from the root of the plant Curcuma longa Linn., has been demonstrated to inhibit carcinogenesis of murine skin, stomach, intestine and liver. However, the toxicology, pharmacokinetics and biologically effective dose of curcumin in humans have not been reported. This prospective phase-I study evaluated these issues of curcumin in patients with one of the following five high-risk conditions: 1) recently resected urinary bladder cancer; 2) arsenic Bowen's disease of the skin; 3) uterine cervical intraepithelial neoplasm (CIN); 4) oral leucoplakia; and 5) intestinal metaplasia of the stomach. Curcumin was taken orally for 3 months. Biopsy of the lesion sites was done immediately before and 3 months after starting curcumin treament. The starting dose was 500 mg/day. If no toxicity > or = grade II was noted in at least 3 successive patients, the dose was then escalated to another level in the order of 1,000, 2,000, 4,000, 8,000, and 12,000 mg/day. The concentration of curcumin in serum and urine was determined by high pressure liquid chromatography (HPLC). A total of 25 patients were enrolled in this study. There was no treatment-related toxicity up to 8,000 mg/day. Beyond 8,000 mg/day, the bulky volume of the drug was unacceptable to the patients. The serum concentration of curcumin usually peaked at 1 to 2 hours after oral intake of crucumin and gradually declined within 12 hours. The average peak serum concentrations after taking 4,000 mg, 6,000 mg and 8,000 mg of curcumin were 0.51 +/- 0.11 microM, 0.63 +/- 0.06 microM and 1.77 +/- 1.87 microM, respectively. Urinary excretion of curcumin was undetectable. One of 4 patients with CIN and 1 of 7 patients with oral leucoplakia proceeded to develop frank malignancies in spite of curcumin treatment. In contrast, histologic improvement of precancerous lesions was seen in 1 out of 2 patients with recently resected bladder cancer, 2 out of 7 patients of oral leucoplakia, 1 out of 6 patients of intestinal metaplasia of the stomach, I out of 4 patients with CIN and 2 out of 6 patients with Bowen's disease. In conclusion, this study demonstrated that curcumin is not toxic to humans up to 8,000 mg/day when taken by mouth for 3 months. Our results also suggest a biologic effect of curcumin in the chemoprevention of cancer.

An analysis of excitatory amino acids, nitric oxide, and prostaglandin E2 in the cerebrospinal fluid of pregnant women: the effect on labor pain.

UNLABELLED: It is still unclear which neurotransmitters are involved in labor pain. We measured the concentrations of excitatory amino acids, nitric oxide, and prostaglandin E2 in the cerebrospinal fluid (CSF) of pregnant women, particularly in those with labor pain. The patients included in the study consisted of women who underwent cesarean delivery either with labor pain (Labor Pain group, n = 40) or without labor pain (Nonlabor Pain group, n = 58). All patients received spinal anesthesia (intrathecal injection of 10-12 mg of bupivacaine) for the operation, and 2 mL of CSF was collected before bupivacaine injection. Concentrations of aspartate and glutamate (0.50 +/- 0.06 microM and 0.79 +/- 0.10 microM, respectively) were significantly larger in the Labor Pain group than in the Nonlabor Pain group (0.35 +/- 0.03 microM and 0.54 +/- 0.04 microM, P < 0.05). There were no significant differences in the concentrations of nitric oxide and prostaglandin E2 between the groups. A positive correlation was found between CSF concentrations of excitatory amino acids and labor pain. IMPLICATIONS: The excitatory amino acids, aspartate and glutamate, play a role in labor pain. N-methyl-D-aspartate receptor antagonists may be useful for labor pain and postlabor uterine contraction pain relief.

Specific IgA antibodies to recombinant early and nuclear antigens of Epstein-Barr virus in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma is a common cancer in Taiwan. The Epstein-Barr virus (EBV) is closely associated with nasopharyngeal carcinoma. The sera of patients with nasopharyngeal carcinoma have IgA antibodies to a variety of EBV latent and replicated antigens. Recently, an enzyme-linked immunosorbent assay (ELISA) kit, combining both the EBV early antigen (EA) and nuclear antigen (EBNA-1) became commercially available. The purpose of this study was to assess its clinical application. Serum IgA antibodies to the EBV EA and EBNA-1 were measured by using the ELISA kit in various groups of subjects. Fluorescence antibody (FA) tests against EBV viral capsid antigen (VCA) and EA in the IgA and IgG classes were also studied for comparison. The DNA content analysis was also carried out to investigate the association with IgA antibody titres using ELISA. The sensitivity, specificity and accuracy of the ELISA test were 98.1%, 81.8% and 88.7% respectively. It was far better than any FA tests. The IgA antibody titres showed no association with DNA content analysis. Univariate analysis of various factors revealed that IgA antibody titres were statistically correlated to N stage (P = 0.0291) and M status (P = 0.001). However, there was no association with the age, sex, T stage and clinical stage. Multivariate analysis of various factors was found to be statistically significant in patients with T4 (P = 0.0133), N3 (P = 0.0244) or M1 (P = 0.001) respectively. Serial testing of antibody titres in 22 previously untreated patients found a trend of decreasing IgA antibody titres after initial treatment when the tumours disappeared (P = 0.0358). The ELISA kit to identify specific IgA antibodies with the combination of EBV EA and EBNA-1 recombinant antigens has high sensitivity and acceptable specificity and accuracy in the diagnosis of nasopharyngeal carcinoma. This assay should be useful for early diagnosis and mass screening of patients.

Failure of grommet insertion in post-irradiation otitis media with effusion.

Nasopharyngeal carcinoma (NPC) survivors with post-irradiation otitis media with effusion (OME; 100 ears) were divided into 2 groups. One group underwent grommet insertion, and the other group was treated by repeated myringotomies plus aspiration to evaluate the outcome of the OME. Computed tomography, magnetic resonance imaging, audiometry, and local checks of the ear, nose, and nasopharyngeal fields were performed to evaluate the sinus and middle ear conditions over a long-term (more than 10 years) follow-up period. The results in these NPC survivors with OME indicated that the prevalence of middle ear complications in the myringotomized group (33%) was less than that in the grommeted group (90%). Grommets alone cannot eradicate inflammation outside the middle ear cavity, but rather, they can aggravate it by superinfection. We therefore recommend that controlling the radiation-induced inflammation in areas such as the ears, nose, sinuses, and nasopharynx is most important. In conclusion, post-irradiation OME should be treated in a different way from conventional OME. Restated, grommet insertion is contraindicated in post-irradiation OME.

Factors affecting the overall survival after salvage surgery in patients with recurrent nasopharyngeal carcinoma at the primary site: experience with 60 cases.

OBJECTIVE: To analyze the factors affecting overall survival after salvage surgery in patients with recurrent nasopharyngeal carcinoma at the primary site after a full course of radiotherapy. DESIGN: Retrospective analysis of 60 consecutive patients treated by surgical resection of the recurrent tumors, with a mean follow-up of 43.1 months (range, 19-96 months). SETTING: Academic tertiary referral center. RESULTS: The overall survival and locoregional relapse-free survival were 56% and 60% at 2 years, respectively, and 30% and 40% at 5 years. Twenty-nine (81%) of 36 patients died with uncontrolled local disease. The T stage of the recurrent tumors appeared to be an important prognostic factor. Age, sex, pathologic findings, and disease-free interval (time between previous radiotherapy and local recurrence) were not significant prognosis-affecting factors by the log-rank test. Multivariate analysis showed that patients with recurrent tumors of undifferentiated carcinoma, sarcoma, or small cell carcinoma had unfavorable prognoses. Uncontrolled local disease and the emergence of distant metastasis predicted grave results as well. Postoperative irradiation showed some benefit to patients, but the difference was not statistically significant. CONCLUSIONS: The T stage of the recurrence was the prominent prognosis-affecting factor in patients with recurrent nasopharyngeal carcinoma who received salvage surgery. Patients with local recurrence should be carefully selected for the salvage surgery. We recommend this surgery for patients with rT1, rT2, or limited rT3 lesions. The results of surgical resection in terms of local control and overall survival were slightly better than those of high-dose reirradiation, with fewer late complications.

Intracranial relapse of nasopharyngeal carcinoma manifested as sudden deafness.

OBJECTIVE: To differentiate tumor relapse from postirradiation sudden deafness (PISD) in patients with nasopharyngeal carcinoma (NPC). STUDY DESIGN: A retrospective study from December 1991 to November 1999. SETTING: University hospital. PATIENTS: Twenty-five irradiated NPC patients with sudden deafness were investigated. All patients received local examination of ears, nose, nasopharynx, and throat fields, as well as a battery of audiologic and neurotologic tests. RESULTS: Three patients with sudden deafness within 3 years after irradiation received a diagnosis of tumor relapse. Magnetic resonance imaging revealed cerebellopontine angle metastasis in one and intracranial invasion in two. Comparison of the remaining 22 NPC patients who had PISD showed that the mean interval between the completion of irradiation to the onset of sudden deafness was 10+/-5 years. CONCLUSION: Magnetic resonance imaging should be performed to exclude intracranial relapse if sudden deafness develops in a patient with NPC within 5 years after irradiation.

Use of bacterially expressed EBNA-1 protein cloned from a nasopharyngeal carcinoma (NPC) biopsy as a screening test for NPC patients.

EBV serological tests have been used for many years as accessory diagnostic predictors of nasopharyngeal carcinoma (NPC). To increase the sensitivity and specificity of the NPC detection rate, a novel enzyme-linked immunosorbent assay (ELISA) was established using a bacterially-expressed GST-EBNA-1 protein, containing the EBNA-1 sequence cloned from an NPC patient. Serum samples were collected from age- and gender-matched patients with NPC, community control subjects and hospital control patients and tested using this ELISA. The positivity rates were 78.7% (247/314) in NPC, 11.5% (28/244) in hospital controls and 3.8% (10/263) in the community control group. These serum samples were also tested for IgA anti-VCA antibodies and their ability to neutralize EBV DNase and the sensitivities of the anti-VCA antibody and DNase-neutralization tests also were analyzed. The optimum combination is VCA plus EBNA-1, which can identify 92.5% (287/310) of NPC patients, and shows a specificity of 92.7% (242/261) for normal individuals.

Serologic markers of Epstein-Barr virus infection and nasopharyngeal carcinoma in Taiwanese men.

BACKGROUND: It is probable but unproven that Epstein-Barr virus (EBV) has a role in nasopharyngeal carcinoma. We determined whether antibodies against EBV are present before the development of nasopharyngeal carcinoma. METHODS: A total of 9699 men were enrolled between 1984 and 1986. Blood samples were examined for IgA antibodies against EBV capsid antigen and neutralizing antibodies against EBV-specific DNase. During 131,981 person-years of follow-up, 22 pathologically confirmed new cases of nasopharyngeal carcinoma that were diagnosed more than one year after recruitment were ascertained through linkage with the National Cancer Registry of Taiwan. RESULTS: The cumulative risk of nasopharyngeal carcinoma per 100,000 person-years was 11.2 for subjects who tested positive for neither serologic marker, 45.0 for those who had one marker, and 371.0 for those who had both markers. After adjustment for age and the presence or absence of a family history of nasopharyngeal carcinoma, the relative risk of nasopharyngeal carcinoma was 32.8 for subjects with both markers (95 percent confidence interval, 7.3 to 147.2; P<0.001) and 4.0 for subjects with one marker (95 percent confidence interval, 1.6 to 10.2; P=0.003), as compared with subjects with neither marker. The longer the duration of follow-up, the greater the difference in the cumulative incidence of nasopharyngeal carcinoma between seropositive and seronegative subjects. CONCLUSIONS: IgA antibodies against EBV capsid antigen and neutralizing antibodies against EBV DNase are predictive of nasopharyngeal carcinoma.