[A multicenter, randomized, open and positive parallel controlled clinical study of clotrimazole vaginal expansion suppository and vaginal tablet in the treatment of mild and moderate vulvovaginal candidiasis].

Objective: Using clotrimazole vaginal tablet as a positive control, to evaluate the results of clotrimazole vaginal expansion suppository in the treatment of mild and moderate vulvovaginal candidiasis in terms of efficacy, patient satisfaction, side effects, and recurrence rate. Methods: This study was jointly conducted by 5 hospitals from August 2017 to October 2018, patients with mild and moderate vulvovaginal candidiasis confirmed by fungal culture and symptoms scores were selected. They were randomized to experimental group and control group as 1∶1 ratio. In the experimental group (n=105), the subjects applied clotrimazole vaginal expansion suppository (150 mg) daily at night for 7 days. In the control group (n=106), the subjects used a single dose of clotrimazole vaginal tablet (500 mg). Follow-ups were performed at (8±3) and (30±5) days after the discontinuation of the drugs, respectively. The difference in clinical symptoms and signs scores was used to evaluate the improvement of clinical symptoms, and the patient's satisfaction and side effects were recorded. Results: At the first follow-up, the experimental group and control group were followed up by fungal culture on the cure rate [66.7% (70/105) versus 63.2% (67/106), P>0.05] and total effective rate [98.1% (103/105) versus 99.1% (105/106), P>0.05], the differences were not statistically significant. At the second follow-up, the recurrence rates of the experimental group and the control group were 5.7% (4/70) and 14.9% (10/67), respectively, with no significant difference (P>0.05). In the evaluation of patient satisfaction, the leakage of the drug in the experimental group was significantly better than that in the control group (P<0.01). The side effects mainly included vaginal stimulation, itching and burning sensation, and there was no statistical difference between the two groups (χ2=1.070, P=0.586). Conclusions: In the treatment of mild and moderate vulvovaginal candidiasis, clotrimazole vaginal expansion suppository is no less effective than clotrimazole vaginal tablet, and there is no significant difference in the recurrence rate between the two. In terms of patient satisfaction, clotrimazole vaginal expansion suppository is superior to clotrimazole vaginal tablet.

A Randomized Assessor-Blinded Wait-List-Controlled Trial to Assess the Effectiveness of Acupuncture in the Management of Chemotherapy-Induced Peripheral Neuropathy.

PURPOSE: Chemotherapy-induced peripheral neuropathy is a complex side effect with few available treatment options. The aim of the study was to test the effectiveness of an 8-week course of acupuncture in the management of chemotherapy-induced peripheral neuropathy in cancer patients who were receiving or had received neurotoxic chemotherapy. METHODS: Randomized assessor-blinded controlled trial with 2 arms; one arm received acupuncture twice weekly for 8 weeks, while the other arm was a wait-list control group receiving only standard care. Primary outcome was pain intensity and interference over the past week using the Brief Pain Inventory at the end of the intervention. Secondary outcomes included clinical assessment (CTCAE [Common Toxicity Criteria for Adverse Events] grading and Total Neuropathy Score-Clinical Version) and nerve conduction studies; and patient-reported outcome measures (Functional Assessment of Cancer Therapy-Gynecologic Oncology Group-Neurotoxicity Quality of Life scale and Symptom Distress Scale) assessed at baseline, end of treatment (8 weeks), week 14, and week 20 from the beginning of treatment. RESULTS: Eighty-seven patients were randomized to the experimental arm (n = 44) and to the standard care wait-list control arm (n = 43). Significant changes at 8 weeks were detected in relation to primary outcome (pain), the clinical neurological assessment, quality of life domains, and symptom distress (all P < .05). Improvements in pain interference, neurotoxicity-related symptoms, and functional aspects of quality of life were sustained in the 14-week assessment ( P < .05), as were physical and functional well-being at the 20-week assessment ( P < .05). CONCLUSIONS: Acupuncture is an effective intervention for treating chemotherapy-induced peripheral neuropathy and improving patients' quality of life and experience with neurotoxicity-related symptoms with longer term effects evident.

Retrospective Cohort Study to Compare Anesthesia in Living Donor Liver Transplantation Recipients Who Received Single and Dual Liver Grafts.

OBJECTIVE: Dual graft living donor liver transplantation (LDLT) is an alternative way to overcome small-for-size syndrome in LDLT. Surgical technique and outcome of using dual grafts have been reported, but there are no reports regarding anesthetic management. The aim of the current study is to compare the anesthetic management of single graft and dual graft liver transplantation. METHODS AND PATIENTS: Anesthesia records of 24 single graft liver transplantation recipients (GI) and 6 dual graft recipients (GII) were reviewed, analyzed, and compared retrospectively. Patient characteristics and intraoperative data between groups were compared with Mann-Whitney t test and Fisher's exact test where appropriate. P value less than .05 was regarded as significant. RESULTS: Patient characteristics and most of the intraoperative data were similar between groups. Significant difference was noted in the total anesthesia time and the anhepatic time. Both times were significantly longer in GII compared to GI. CONCLUSION: Dual graft living donor liver transplantation is surely a technically more challenging and demanding procedure. Therefore the total anesthesia time is longer, especially the anhepatic phase, because there are more graft vessels to be reconstructed before reperfusion. Overall the anesthetic management in terms of blood transfusion, fluid administration, sodium bicarbonate, calcium supplement, and the number of patients requiring fractional diluted noradrenaline support for maintenance of acceptable hemodynamic were not much different between the 2 groups.

A thin-layer chromatography-bioautographic method for detecting dipeptidyl peptidase IV inhibitors in plants.

A thin-layer chromatography (TLC)-bioautographic method was developed with the aim to detect dipeptidyl peptidase IV (DPP IV) inhibitors from plant extracts. The basic principle of the method is that the enzyme (DPP IV) hydrolyzes substrate (Gly-Pro-p-nitroaniline) into p-nitroaniline (pNA), which diazotizes with sodium nitrite, and then reacts with N-(1-naphthyl) ethylenediamine dihydrochloride in turn to form a rose-red azo dye which provides a rose-red background on the TLC plates. The DPP IV inhibitors showed white spots on the background as they blocked enzymolysis of the substrate to produce pNA. The method was validated with respect to selectivity, sensitivity, linearity, precision, recovery, and stability after optimizing key parameters including plate type, time and temperature of incubation, concentration of substrate, enzyme and derivatization reagents, and absorption wavelength. The results showed good lineary within amounts over 0.01-0.1µg range for the positive control, diprotin A, with the coefficient of determination (r(2))=0.9668. The limits of detection (LOD) and quantification (LOQ) were 5 and 10ng, respectively. The recoveries ranged from 98.9% to 107.5%. The averages of the intra- and inter-plate reproducibility were in the range of 4.1-9.7% and 7.6-14.7%, respectively. Among the nine methanolic extracts of medicinal herbs screened for DPP IV inhibitors by the newly developed method, Peganum nigellastrum Bunge was found to have one white active spot, which was then isolated and identified as harmine. By spectrophotometric method, harmine hydrochloride was found to have DPP-IV inhibitory activity of 32.4% at 10mM comparing to that of 54.8% at 50µM for diprotin A.

The effect of probiotics on serum levels of cytokine and endotoxin in peritoneal dialysis patients: a randomised, double-blind, placebo-controlled trial.

Inflammatory markers such as interleukin (IL)-6 and tumour necrosis factor-alpha (TNF-α) are elevated in dialysis patients and can predict cardiovascular events and all-cause mortality. Endotoxin is an important source and also another marker of inflammation in patients with chronic kidney disease. The aim of this study was to evaluate the impact of oral probiotics on serum levels of endotoxemia and cytokines in peritoneal dialysis (PD) patients. The decline of residual renal function, peritonitis episodes, and cardiovascular events were also recorded. From July 2011 to June 2012, a randomised, double-blind, placebo-controlled trial was conducted in PD patients. The intervention group received one capsule of probiotics containing 10(9) cfu Bifobacterium bifidum A218, 10(9) cfu Bifidobacterium catenulatum A302, 10(9) cfu Bifidobacterium longum A101, and 10(9) cfu Lactobacillus plantarum A87 daily for six months, while the placebo group received similar capsules containing maltodextrin for the same duration. Levels of serum TNF-α, interferon gamma, IL-5, IL-6, IL-10, IL-17, and endotoxin were measured before and six months after intervention. 39 patients completed the study (21 in the probiotics group and 18 in the placebo group). In patients receiving probiotics, levels of serum TNF-α, IL-5, IL-6, and endotoxin significantly decreased after six months of treatment, while levels of serum IL-10 significantly increased. In contrast, there were no significant changes in levels of serum cytokines and endotoxin in the placebo group after six months. In addition, the residual renal function was preserved in patients receiving probiotics. In conclusion, probiotics could significantly reduce the serum levels of endotoxin, pro-inflammatory cytokines (TNF-α and IL-6), IL-5, increase the serum levels of anti-inflammatory cytokine (IL-10), and preserve residual renal function in PD patients.

Effects of supplemental glutamine on growth performance, plasma parameters and LPS-induced immune response of weaned barrows after castration.

Two experiments were conducted to investigate the effects of supplemental glutamine on growth performance, plasma parameters and LPS-induced immune response of weaned barrows after castration. In experiment 1, forty-eight weaned male piglets were used and fed maize and soybean meal diets supplemented with 0 (Control) or 2% L-Gln (Gln+) for 25 days. The results indicated that the Gln+ group tended to increase average daily gain compared to control in stages of days 7 to 14 and 0 to 25. The Gln+ had significantly better feed efficiency than the control group did during days 14 to 25 and 0 to 25. The plasma blood urea nitrogen and alkaline phosphatase contents of Gln+ group were higher than those of the control group on day 14 post-weaning. In experiment 2, sixteen weaned male piglets were injected with E. coli K88+ lipopolysaccharide (LPS) on day 14 post-weaning. The results showed that the Gln+ group had lower concentrations of plasma adrenocorticotrophic hormone and cortisol than the control group on day 14 pre-LPS challenge. In addition, Gln+ group had higher plasma IgG concentration than the control group for pre- or post-LPS challenged on day 14 post-weaning. In summary, dietary supplementation of Gln was able to alleviate the stressful condition and inflammation associated with castration in weaned barrows, and to improve their immunity and growth performance in the early starter stage.

Classification and differentiation of the genus Peganum indigenous to China based on chloroplast trnL-F and psbA-trnH sequences and seed coat morphology.

The genus Peganum (Zygophyllaceae) consists of six species and one subspecies; three of which are distributed in China, P. harmala Linn, P. nigellastrum Bunge and P. multisectum (Maxim.) Bobr. A probable new or intermediate species, Peganum sp., has been suggested in the wild in northwest China. Traditional classification in genus Peganum has focused on hairs on the plant surface. In this study, seed coat characteristics of Peganum species were investigated using light and scanning electron microscopy, demonstrating clear differences in morphology between species. In addition, DNA sequence data from two sequences (chloroplast: trnL-F, psbA-trnH) were used to differentiate Peganum sp. and study polygenetic relationships. Diversity in DNA sequences among Peganum species was found, with inter-specific sequence divergence ranging from 0.6% to 5.6% in psbA-trnH, and 0.0% to 1.8% in trnL-F. The variations within species were low: from 0.0% to 0.4% in psbA-trnH and 0.0% to 0.4% in trnL-F. Therefore, Peganum species can now be easily identified as separate entities based on variations in DNA sequences. Phylogenetic trees were constructed from the combined data set for the two gene fragments, and the results indicate that Peganum sp. is monophyletic and sister to P. harmala and P. nigellastrum, while P. multisectum is also monophyletic. DNA data further confirmed that P. multisectum is an independent species and that a new species, Peganum sp., exists within the genus Peganum growing wild in China.

Comparison of therapeutic results in sudden sensorineural hearing loss with/without additional hyperbaric oxygen therapy: a retrospective review of 465 audiologically controlled cases.

OBJECTIVE: To investigate the necessity of routine application of hyperbaric oxygen therapy for sudden sensorineural hearing loss. DESIGN/SETTING AND PARTICIPANTS: A retrospective chart review looked at 465 patients, with 353 of them receiving pharmacologic treatments alone. Among these patients, 76 underwent systemic steroid treatment only (steroid group) and 277 received systemic steroids and dextran (steroid-dextran group). The remaining 112 patients were treated with hyperbaric oxygen in addition to pharmacologic agents (steroid-dextran-hyperbaric oxygen group). MAIN OUTCOME MEASURES: The outcome was determined by comparing the difference of pure-tone thresholds and absolute hearing gains after treatment calculated at each audiometric octave frequency or grouped frequencies of audiograms. On the basis of the severity of initial hearing loss, patients were classified at three scales of hearing impairments measured in decibels hearing level (dBHL): ≦ 70 dBHL, less severe; 71-90 dBHL, severe; and ≧ 91 dBHL, profound. The outcomes of their hearing recovery were classified into three recovery grades: good, fair and poor. RESULTS: In those patients with initial hearing loss >90 dBHL, the addition of hyperbaric oxygen to steroid-dextran gave a significant hearing gain difference (P = 0.030) by showing a greater hearing gain of 24.5 ± 2.7 dB compared with steroid only (12.9 ± 3.7 dB) or steroid-dextran (15.6 ± 2.7 dB). This outcome was confirmed when we compared the outcome using the recovery grading; steroid-dextran-hyperbaric oxygen group showed that more patients with initial profound (≧ 91 dBHL) hearing loss responded to hyperbaric oxygen treatment by exhibiting good and fair recoveries (2% and 70%) as compared with steroid only (0% and 42%) or steroid-dextran (8% and 46%) groups (P = 0.043), while the patients with initial severe (71-90 dBHL) and less severe (≦ 70 dBHL) hearing loss responded to the addition of hyperbaric oxygen treatment with less favourable recoveries. Furthermore, the addition of dextran in steroid-dextran group showed no significant benefit compared with the steroid group (P = 0.435). CONCLUSIONS: When applied as an adjuvant to pharmacologic agents, hyperbaric oxygen benefits patients with initial profound sudden sensorineural hearing loss. Therefore, we recommend the routine application of hyperbaric oxygen in conjunction with pharmacologic agents for those patients. The addition of dextran to steroid has no benefit and cannot be recommended.

Synchrotron microangiography studies of angiogenesis in mice with microemulsions and gold nanoparticles.

We present an effective solution for the problem of contrast enhancement in phase-contrast microangiography, with the specific objective of visualising small (<8 microm) vessels in tumor-related microangiogenesis. Different hydrophilic and hydrophobic contrast agents were explored in this context. We found that an emulsified version of the hydrophobic contrast agents Lipiodol provides the best contrast and minimal distortion of the circulation and vessel structure. Such emulsions are reasonably biocompatible and, with sizes of 0 +/- 0.8 microm, sufficient to diffuse to the smallest vessel and still provide reasonable contrast. We also explored the use of Au nanoparticle colloids that could be used not only to enhance contrast but also for interesting applications in nanomedicine. Both the Lipiodol microemulsions and Au nanoparticle colloids can be conjugated with medicines or cell specific labeling agents and their small size can allow the study of the diffusion of contrast agents through the vessel leakage. This enables direct imaging of drug delivery which is important for cancer treatment.

Progress in cell membrane chromatography.

Cell membrane chromatography (CMC) was first established by He et al. in 1996. A bioaffinity chromatography technique, CMC has since proven to be an important method for studying drug-receptor interactions and screening active compounds from medicinal herbs. This paper briefly reviews the characteristics of the cell membrane stationary phase (CMSP), the CMC analytical system, and its applications.

Regaining consciousness for prolonged comatose patients with right median nerve stimulation.

During the past half year, we have utilized right median nerve stimulation (produced by Empi. Co. USA) to awaken consciousness of patients on 6 cases, 2 with brain trauma, one with aneurysm rupture, one with hemorrhagic stroke and two with hypoxic encephalopathy. The comatose duration ranged from 6 to 17 weeks. All patients underwent SPECT scan for cerebral perfusion evaluation and neurotransmitter quantification before and after the stimulation. The stimulation time lasted from 8 to 10 hours on daytime. The stimulation persisted for 3 months in all patients. Four patients recovered from the consciousness within 35 days. There was no obvious clinical improvement in two patients. Brain perfusion increased in all cases through the SPECT study after stimulation. The elevation of neurotransmitter in CSF was found in 5 out of the 6 cases. Median nerve stimulation elevates the cerebral blood flow and may influence the patient's consciousness. Young patients (<40 years old) had better results than old patients. The stimulation could be initiated if the patient's acute stage was over. In our series, although increase in cerebral blood flow was found in all cases, some patients did not regain consciousness.

Multiple deep-seated cavernomas in the third ventricle, hypothalamus and thalamus.

BACKGROUND: Cavernomas are rarely located in the third ventricle, hypothalamus, or thalamus. In this report, we present our experience managing a patient with three cavernomas, one each in the floor of the third ventricle, hypothalamus, and left thalamus. CASE PRESENTATION: This 62-year-old woman had had an unsteady gait and weakness of both legs for six months. Magnetic resonance imaging (MRI) revealed multiple intracranial tumours in the third ventricle, hypothalamus, and left thalamus. The third ventricle tumour was found to be a cavernoma by intra-operative endoscopic examination and then was excised via a transcortical, transventricular approach. Pathology revealed a cavernoma. The other two tumours were assumed to be cavernomas because of their MRI features. Three days after surgery, the patient developed right hemiparesis and disturbance of consciousness. Computed tomography revealed a left thalamic haemorrhage. After conservative treatment, her conscious level gradually recovered and she could walk with support seven months after surgery. INTERPRETATION: Our experience with this rare case of multiple, deep-seated cavernomas suggests that management of such patients requires specific consideration of the clinical manifestations, location, size, and previous bleeding history.

Release of paclitaxel from polylactide-co-glycolide (PLGA) microparticles and discs under irradiation.

Paclitaxel is a promising anti-cancer drug as well as a radiosensitizer for chemotherapy and radiotherapy applications. Because of the poor solubility of paclitaxel in water and most pharmaceutical reagents, it is usually formulated with an adjuvant called Cremophor EL, which causes severe side effects. This work develops new dosage forms of paclitaxel for controlled release application, which do not require the adjuvant and, thus, can avoid its associated side effects. Paclitaxel was encapsulated into the PLGA matrix with various additives such as polyethylene glycol (PEG), isopropyl myristate (IPM) and d-alpha tocopheryl polyethylene glycol (Vitamin E TPGS). These additives were used to enhance the release rate of paclitaxel from the polymer matrix. Spray-drying and an hydraulic press were used to prepare paclitaxel-PLGA microspheres and discs. The microspheres and discs were given different irradiation doses to investigate their effects on the surface morphology (characterized by SEM, AFM and XPS) and in vitro release properties. There seems to be a small effect of the ionizing radiation on various formulations. Although the irradiation did not cause observable changes on the morphology of the polymer matrix, the release rate can be enhanced by a few per cent. It was found that PEG has the highest enhancement effect for release rate among all the additives investigated in this study.

Clinical and biological implications of partial tandem duplication of the MLL gene in acute myeloid leukemia without chromosomal abnormalities at 11q23.

The clinical and biological features of acute myeloid leukemia (AML) with 11q23/MLL translocations are well known, but the characteristics of AML with partial tandem duplication of the MLL gene have not been explored comprehensively. In this study, MLL duplication was analyzed, in 81 AML patients without chromosomal abnormalities at 11q23, using Southern blotting, genomic DNA polymerase chain reaction (PCR), reverse-transcription PCR and complementary DNA sequencing. Nine patients showed partial tandem duplication of the MLL gene, including eight (12%) of the 68 with normal karyotype. Seven patients showed fusion of exon 6/exon 2 (e6/e2), one, combination of differentially spliced transcripts e7/e2 and e6/e2, and the remaining one, combination of e8/e2 and e7/e2. Among the patients with normal karyotype, children aged 1 to 15 showed a trend to higher frequency of MLL duplication than other patients (2/5 or 40% vs 6/62 or 10%, P = 0.102). The patients with tandem duplication of the MLL gene had a significantly higher incidence of CD11b expression on leukemic cells than did those without in the subgroup of patients with normal karyotype (75% vs 28%, P = 0.017). There were no significant differences in the expression of lymphoid antigens or other myeloid antigens between the two groups of patients. In adults, the patients with MLL duplication had a shorter median survival time than those without (4.5 months vs 12 months, P = 0.036). In conclusion, partial tandem duplication of the MLL gene is associated with increased expression of CD11b on leukemic blasts and implicates poor prognosis in adult AML patients. The higher frequency of MLL duplication in children older than 1 year, than in other age groups, needs to be confirmed by further studies.

Intra-arterial plus i.v. chemotherapy for advanced bulky squamous cell carcinoma of the buccal mucosa.

From July 1994 to December 1996, 41 patients with previously untreated, advanced bulky squamous cell carcinoma arising from the buccal mucosa (BSCC) were enrolled. All patients were males with a median age of 47 years (range 29-72). The tumor extent was stage III/IV: three of 38, T4: 85%, N2-3: 20%. Patients were initially scheduled to receive intra-arterial (i.a.) chemotherapy, followed by i.v. chemotherapy and regional therapy. The i.a. chemotherapy catheter was properly placed by external carotid artery angiography via the femoral artery. The i.a. chemotherapy consisted of cisplatin (P) 100 mg/m(2) day 1 plus 5-fluorouracil (F) 1000 mg/m(2) day 1-4, and the i.v. chemotherapy consisted of PF (10 patients) or PF plus methotrexate 200 mg/m(2) day 15 and 22 (31 patients). All chemotherapy regimens were administered at 4-week intervals. The response rate of i.a. plus i.v. chemotherapy for the primary site was 85% (35 of 41) with 29% complete remission (CR) (12 of 41). The response and CR rates of neck nodes were 82% (14 of 17) and 41% (seven of 17), respectively. The combined overall response rate was 80% (33 of 41) with a 29% CR (12 of 41). Major toxicity from i.a. chemotherapy of WHO grade > or = 3 included: mucositis of infusion area (76%), hemialopecia (56%) and leukopenia (5%). Three neurologic complications of i.a. chemotherapy including one hemiparesis occurred. The median follow-up time was 47 months (range 36-66 months), and the overall survival and disease-free survival were both 34% (14 of 41). Four patients were cured with chemotherapy alone and eight patients (19.5%) were cured without surgical intervention. Using i.a. chemotherapy as a cytoreductive therapy followed by subsequent i.v. chemotherapy produces a high response rate and an encouraging degree of complete response rate in advanced bulky BSCC. However, toxicity management and catheter placement will need to be improved in order to better define the role of this therapy in advanced BSCC.

Weekly high-dose 5-fluorouracil (5-FU), leucovorin (LV) and bimonthly cisplatin in patients with advanced gastric cancer.

BACKGROUND: A phase II clinical trial was performed to evaluate the activity and toxicity of bimonthly cisplatin and weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin in patients with advanced gastric cancer. PATIENTS AND METHODS: From September 1997 to March 1998, 23 chemo-naive patients of advanced gastric cancer were enrolled in this study. The regimen consisted of weekly 24-h infusion of 5-FU (2,600 mg/m2) and LV 150 mg and bimonthly cisplatin (25-50 mg/m2) bolus for 12 weeks followed by a 2-week break. RESULTS: There were 10 male and 13 female patients with a median age of 52 years. A total of 428 chemotherapy treatments were given with a mean of 11. Seventeen patients were evaluable for response. There were 41% (7/17) partial response, 18% (3/17) stable disease and 41% (7/17) progressive disease. The grade III or IV toxicity included anorexia 35% (8/23), fatigue 26% (6/23), vomiting 17% (4/23) and mucositis 9% (2/23). One patient developed perforated duodenal stump after chemotherapy. One patient died of hyperammonemia-related coma. The median times to disease progression and overall survival were 3.5 and 7 months, respectively. CONCLUSIONS: This regimen showed modest activity against gastric cancer. However, there was no survival advantage and there was greater toxicity than with weekly high-dose 5-FU-LV alone.

Impact of oral submucous fibrosis on chemotherapy-induced mucositis for head and neck cancer in a geographic area in which betel quid chewing is prevalent.

In Southeast Asia and Taiwan, betel quid chewing is prevalent. Patients with head and neck cancer who chewed betel quid habitually seem to experience more severe chemotherapy-induced mucositis in our clinical practice. To validate this issue, patients with untreated head and neck cancer who received cisplatin (cDDP) plus a 5-fluorouracil (5-FU)-based neoadjuvant chemotherapy were included in this analysis. Information on the consumption of betel quid, tobacco, and alcohol were recorded before chemotherapy. Oral submucous fibrosis (OSF) was diagnosed clinically according to the fibrotic appearance of the mucosa and trismus. Mucositis was scored according to the World Health Organization criteria, and the mucositis score of the first course of chemotherapy was used for analysis. From December 1993 to April 1996, 120 patients were enrolled in this trial. Neither the betel quid chewing nor the cancer of the oral cavity was to be a significant factor for mucositis. However, clinically diagnosed OSF was found to display a significant correlation with more severe mucositis (p = 0.02). We concluded that in betel quid chewing-prevalent areas, OSF was a risk factor of more severe mucositis in head and neck cancer patients treated by CDDP and 5-FU-based regimens.

Weekly 24-h infusion of high-dose 5-flurouracil and leucovorin in patients with advanced gastric cancer.

The effect of biochemical modulation of weekly high-dose 5-fluorouracil (5-FU) 24 h infusion by leucovorin (LV) in the treatment of 39 consecutive patients with advanced gastric cancer without prior chemotherapy from October 1996 to August 1997 was examined. There were 21 male and 18 female patients with a median age of 56 years. The regimen consisted of 5-FU 2600 mg/m2 and LV 150 mg administered by 24 h infusion weekly for 6 weeks followed by a 2 week break. The treatment was repeated every 8 weeks until disease progression, patient refusal or unacceptable toxicity. Placement of a central vascular device and a portable external infusion pump was required in all patients and was used for outpatient treatment. The response to treatment was evaluated every 8 weeks. A total of 395 chemotherapy treatments were given with a mean of 10 (2-24). This response rate was: 33% (12 of 36) partial response (PR) rate, 33% (12 of 36) stable disease (SD) and 33% (12 of 36) progressive disease (PD). In general, the toxicity was mild but two toxic deaths occurred, one due to neutropenic sepsis and the other due to hyperammonemia. The median time to progression was 4 months. The overall median survival was 7 months. The survivals of the PR, SD and PD were 12, 8 and 5 months, respectively. This regimen showed a modest activity against gastric cancer with acceptable toxicity. Weekly 24 h infusion of high-dose 5-FU with LV in an outpatient setting for patients with gastric cancer is feasible and deserves further study as a basis for combination therapy.

Clinical benefit and response in patients with gastric cancer to weekly 24-hour infusion of high-dose 5-fluorouracil (5-FU) and leucovorin (LV).

BACKGROUND: A prospective study evaluated the efficacy and correlation of different outcome measurements, including the WHO response criteria and clinical benefit (CB), to weekly high-dose 5-FU and LV for patients with advanced gastric cancer. PATIENTS AND METHODS: Thirty-nine chemotherapy-naive patients were enrolled from Sep. 1996 to Oct. 1997. The treatment consisted of a 24-hour continuous infusion of 5-FU 2600 mg/m2 & LV 150 mg weekly for 6 weeks with a subsequent 2-week break. The responses were evaluated by CB and WHO criteria at the end of the 8th week, then at 8-week intervals. RESULTS: There were 21 male and 18 female patients with a median age of 56 years. The median Karnofsky performance score was 70%. Thirty-six patients were evaluable for WHO criteria, and 12 (33.3%) had partial response, 12 (33.3%) had stable disease and 12 (33.3%) had progressive disease. Twenty-one of the 35 (60%) evaluable patients for CB were found to have a positive response. There was a significant correlation between WHO response and CB. The median survival was 10.5 months for CB responders, while the median survival among the CB non-responders was 5 months only. CONCLUSIONS: This study found that this regimen yielded a 60% CB, despite a 33% WHO response rate. Improvement in CB resulted in an improvement in survival as well as the correlation between CB and WHO response, and suggested the value of CB as an alternative indicator for clinical response.

Correlation between computed tomographic density of lymph node metastases and response to cisplatin-based chemotherapy in patients with head and neck squamous cell carcinoma in an area in which betel quid chewing is prevalent.

BACKGROUND: Identifying the factors predicting response to chemotherapy is important for patients with head and neck squamous cell carcinoma (HNSCC). It allows more rational selection of subsets of patients who may benefit from multidisciplinary treatment. Correlation of lymph node density in contrast-enhanced computed tomographic (CT) scans of HNSCC with response to chemotherapy was observed in the recent literature. This prospective study was designed to validate this clinical issue. METHODS: From January 1992 to March 1995, 71 patients with untreated HNSCC were included in this study in which the following criteria were met: 1) a lymph node > 3 cm by physical examination or > or = 2 cm by scanographic examination; 2) clinically evaluable disease treated by cisplatin-based neoadjuvant chemotherapy; and 3) availability of a pretherapeutic contrast-enhanced CT scan showing the cross-sections of relevant lymph node metastases. The density of the largest lymph node was compared with that of the nuchal muscles by a radiologist blinded to the patient's therapeutic outcome. A lymph node was classified as hypodense if more than 33% of the lymph node surface area was comprised of a hypodense zone, and isodense if less than a third of the lymph node surface area was comprised of a hypodense zone. RESULTS: Fifty-one patients (72%) had the largest lymph node classified as hypodense, and 63 patients (89%) were found to have extranodal spread (ENS) in the relevant lymph nodes. Fifty-nine patients were betel quid chewers. Lymph node density was not related to T classification, primary site, or histologic differentiation of the primary tumor. There was also no correlation between lymph node density and lymph node N classification. The lymph node chemotherapy response rate was 35% (7 of 20) of the isodense group and 47.1% (24 of 51) of the hypodense group (P = 0.36). ENS was found to have no impact on the chemotherapy response. CONCLUSIONS: Computed tomographic density of lymph node metastases did predict chemotherapy response in the HNSCC patients in the current study from an area in which betel quid chewing is prevalent.