Effect of 4-(N,N-dimethylamino)phenethyl Alcohol on Degree of Conversion and Cytotoxicity of Photo-Polymerized CQ-Based Resin Composites

The aim of this study was to evaluate the degree of conversion (DC) and the cytotoxicity of photo-cured experimental resin composites containing 4-(N,N-dimethylamino)phenethyl alcohol (DMPOH) combined to the camphorquinone (CQ) compared with ethylamine benzoate (EDAB). The resin composites were mechanically blended using 35 wt% of an organic matrix and 65 wt% of filler loading. To this matrix was added 0.2 wt% of CQ and 0.2 wt% of one of the reducing agents tested. 5x1 mm samples (n=5) were previously submitted to DC measurement and then pre-immersed in complete culture medium without 10% (v/v) bovine serum for 1 h or 24 h at 37 °C in a humidifier incubator with 5% CO2 and 95% humidity to evaluate the cytotoxic effects of experimental resin composites using the MTT assay on immortalized human keratinocytes cells. As a result of absence of normal distribution, the statistical analysis was performed using the nonparametric Kruskal-Wallis to evaluate the cytotoxicity and one-way analysis of variance to evaluate the DC. For multiple comparisons, cytotoxicity statistical analyses were submitted to Student-Newman-Keuls and DC analysis to Tukey's HSD post-hoc test (=0.05). No significant differences were found between the DC of DMPOH (49.9%) and EDAB (50.7%). 1 h outcomes showed no significant difference of the cell viability between EDAB (99.26%), DMPOH (94.85%) and the control group (100%). After 24 h no significant difference were found between EDAB (48.44%) and DMPOH (38.06%), but significant difference was found compared with the control group (p>0.05). DMPOH presented similar DC and cytotoxicity compared with EDAB when associated with CQ.

O objetivo deste estudo foi avaliar o grau de conversão (GC) e a citotoxicidade de resinas compostas experimentais utilizando o álcool 4-(N,N-dimetilamino) fenil etílico (DMPOH) associado à canforoquinona (CQ) como sistema fotoiniciador (SF) comparado à versão comercial utilizando o benzoato de etilamina (EDAB). Para tanto, as resinas compostas experimentais foram mecanicamente misturadas utilizando (em peso): 35% de matriz orgânica e 65% em peso de partículas de carga. Posteriormente, foram adicionados 0,2% de CQ e 0,2% de um dos agentes redutores testados. Amostras de 5 x 1 mm (n=5) foram previamentes submetidas à análise de GC e posteriormente, esterilizadas e colocadas no meio de cultura completo sem soro fetal bovino estéril por 1 h ou 24 h a 37 °C em encubadora com 5% de CO2 and 95% de umidade para avaliar os efeitos citotóxicos das resinas compostas experimentais utilizando o método MTT emcélulas células humanas imortalizadas de queratinócitos. Os dados de citotoxicidade foram submetidos à análise estatística de Kruskal-Wallis e de GC à análise de variância com um fator. Em virtude da ausência de normalidade, a análise estatística da citotoxicidade foi realizada utilizando-se o teste não-paramétrico de Kruskal-Wallis. Para o GC, os dados foram submetidos à análise de variaância de 1 fator. Posteriormente para múltiplas comparações, os dados de citotoxicidade foram submetidos ao teste Student-Newman-Keuls e o GC ao teste de Tukey's HSD post-hoc (=0.05). Não foi observada diferença estatística entre o GC de DMPOH (49,9%) e EDAB (50,7%). Para os resultados de 1 h não houve diferença na viabilidade celular entre EDAB (99,26%), DMPOH (94,85%) e o grupo controle (100%). Após 24 h, nenhuma diferença estatística foi encontrada entre EDAB (48,44%) e DMPOH (38,06%), entretanto, diferença significativa foi encontrada em relação ao grupo controle (p>0,05). O DMPOH apresentou GC e citotoxicidade semelhante à EDAB quando associado à CQ.

Ground reaction forces during level ground walking with body weight unloading

Background: Partial body weight support (BWS) systems have been broadly used with treadmills as a strategy for gait training of individuals with gait impairments. Considering that we usually walk on level ground and that BWS is achieved by altering the load on the plantar surface of the foot, it would be important to investigate some ground reaction force (GRF) parameters in healthy individuals walking on level ground with BWS to better implement rehabilitation protocols for individuals with gait impairments. Objective: To describe the effects of body weight unloading on GRF parameters as healthy young adults walked with BWS on level ground. Method: Eighteen healthy young adults (27±4 years old) walked on a walkway, with two force plates embedded in the middle of it, wearing a harness connected to a BWS system, with 0%, 15%, and 30% BWS. Vertical and horizontal peaks and vertical valley of GRF, weight acceptance and push-off rates, and impulse were calculated and compared across the three experimental conditions. Results: Overall, participants walked more slowly with the BWS system on level ground compared to their normal walking speed. As body weight unloading increased, the magnitude of the GRF forces decreased. Conversely, weight acceptance rate was similar among conditions. Conclusions: Different amounts of body weight unloading promote different outputs of GRF parameters, even with the same mean walk speed. The only parameter that was similar among the three experimental conditions was the weight acceptance rate. .

TP53 status predicts long-term survival in locally advanced breast cancer after primary chemotherapy.

BACKGROUND: Before the advent of neoadjuvant chemotherapy, radiotherapy and surgery alone were associated with a high risk of uncontrolled locoregional relapses in locally advanced breast cancer (LABC). MATERIAL AND METHODS: In the 1990s we initiated two neoadjuvant protocols, where patients with LABC were given either doxorubicin qW or 5-fluorouracil/mitomycin (FUMI) q3W to shrink the tumours prior to mastectomy and postoperative radiotherapy. Previously, we reported TP53 mutation status to predict a poor response to chemotherapy. Here, we present the long-term survival data, with a follow-up of 20 years in the doxorubicin (n = 90) and 15 years in the FUMI trial (n = 34). RESULTS: Patients in the doxorubicin trial with TP53-mutated tumours experienced a shorter recurrence-free (RFS; 14 vs. 83 months, p < 0.001) and overall survival (OS; 35 vs. 90 months, p < 0.001) than patients with TP53 wt tumours. Similarily, TP53 mutations were associated with a shorter OS (22 vs. 80 months, p = 0.03) and a tendency to shorter RFS (17 vs. 33 months, p = 0.06) in patients treated with FUMI. Furthermore, axillary lymph node metastases predicted shorter OS, but only in patients treated with doxorubicin (49 vs. 142 months, p < 0.04). Applying multivariate analysis, TP53 mutations predicted inferior RFS (p < 0.001) as well as OS (p < 0.001), independently of axillary lymph node status. Isolated local recurrences, without simultaneous distant metastases, occurred in seven patients only in the two trials. Interestingly, chest wall radiation fibrosis predicted improved OS (p = 0.004). CONCLUSION: TP53 inactivating mutations are associated with an inferior long-term prognosis in patients with LABC treated with conventional chemotherapy.

Upfront compared to delayed cytoreductive surgery and perioperative intraperitoneal chemotherapy for pseudomyxoma peritonei is associated with considerably lower perioperative morbidity and recurrence rate.

BACKGROUND: Cytoreductive surgery (CRS) combined with perioperative intraperitoneal chemotherapy (PIC) is a recognized management strategy for pseudomyxoma peritonei. We seek to evaluate the outcomes of patients treated upfront with CRS PIC compared to patients undergoing delayed CRS PIC as salvage or treatment for recurrences after initial debulking surgery. METHODS: Retrospective analysis of patients with low-grade pseudomyxoma peritonei treated within our institution were stratified according to upfront versus delayed CRS PIC after intial debulking surgery. Survival was analyzed using the Kaplan-Meier method and compared using the log-rank test. RESULTS: Of 83 patients treated, 35 patients (42%) underwent upfront and 48 patients (58%) underwent delayed CRS PIC. The peritoneal cancer index (P = 0.048), amount of blood transfusion intraoperatively (P = 0.003) and duration of operation (P = 0.007) was lesser in the upfront compared to delayed group. Upfront treatment confers 5-year recurrence-free survival benefit (77% vs 37%; P = 0.011) and 10-year overall survival benefit (67% vs 35%; P = 0.054) over delayed treatment. CONCLUSION: Upfront CRS PIC seems to confer beneficial perioperative outcomes and lower recurrence rates over delayed CRS PIC. Early referral to centralized treatment centers would seem to be a reasonable strategy to improve outcomes.

[Ex-PRESS miniature glaucoma implant inserted under a scleral flap in open-angle glaucoma surgery: a retrospective study]. / Implant miniature Ex-PRESS placé sous un volet scléral dans la chirurgie du glaucome à angle ouvert: étude rétrospective.

PURPOSE: (1) To present the Ex-PRESS device implanted under a scleral flap in open-angle glaucoma patients and to report its safety and efficacy; (2) to compare the results obtained without a scleral flap in a glaucoma group. PATIENTS AND METHODS: The case series studied included the eyes of Caucasian patients (82 patients, 99 eyes) with open-angle glaucoma, operated on between January 2003 and June 2004. The Ex-PRESS devices were inserted under the scleral flap in the anterior chamber; if necessary a combined surgery was performed (28 eyes). Each patient underwent ophthalmic examinations (IOP, visual field, gonioscopy, cup/disc ratio) before and after the operation. The surgical procedure lasted between 10 and 20 min with topical anesthesia. An antimetabolite was used under the scleral flap for all patients. The mean follow-up was 7.5+/-4.6 months; 40% had 12 months follow-up (40 eyes). RESULTS: The IOP decreased from 22.9+/-5.3 mmHg preoperatively to 14+/-2 mmHg at 6 months and 14.3+/-2.3 mmHg at 1 year. The success rate was 86.9% (IOP below 21 mmHg with or without drugs). Complete success was achieved in 62.6% (IOP below 21 mmHg without anti-glaucoma drops or medications). In 13 eyes, IOP was not controlled with eye drops, and nine eyes had to be reoperated. Six cases presented athalamia but recovered without surgical treatment. We did not observe any infection, corneal erosion, or Ex-PRESS extrusion. There were no statistical differences between results obtained with and without scleral flap regarding IOP or early complications (athalamia). CONCLUSION: Both the safety and the efficacy of the device under a scleral flap were showed in glaucoma surgery in this retrospective study. Using the scleral flap reduces the risk of erosion but confirmation with a longer follow-up is needed.

Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer.

PURPOSE: The 21-gene recurrence score (RS) assay quantifies the likelihood of distant recurrence in women with estrogen receptor-positive, lymph node-negative breast cancer treated with adjuvant tamoxifen. The relationship between the RS and chemotherapy benefit is not known. METHODS: The RS was measured in tumors from the tamoxifen-treated and tamoxifen plus chemotherapy-treated patients in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B20 trial. Cox proportional hazards models were utilized to test for interaction between chemotherapy treatment and the RS. RESULTS: A total of 651 patients were assessable (227 randomly assigned to tamoxifen and 424 randomly assigned to tamoxifen plus chemotherapy). The test for interaction between chemotherapy treatment and RS was statistically significant (P = .038). Patients with high-RS (> or = 31) tumors (ie, high risk of recurrence) had a large benefit from chemotherapy (relative risk, 0.26; 95% CI, 0.13 to 0.53; absolute decrease in 10-year distant recurrence rate: mean, 27.6%; SE, 8.0%). Patients with low-RS (< 18) tumors derived minimal, if any, benefit from chemotherapy treatment (relative risk, 1.31; 95% CI, 0.46 to 3.78; absolute decrease in distant recurrence rate at 10 years: mean, -1.1%; SE, 2.2%). Patients with intermediate-RS tumors did not appear to have a large benefit, but the uncertainty in the estimate can not exclude a clinically important benefit. CONCLUSION: The RS assay not only quantifies the likelihood of breast cancer recurrence in women with node-negative, estrogen receptor-positive breast cancer, but also predicts the magnitude of chemotherapy benefit.

A randomised trial in malignant mesothelioma (M) of early (E) versus delayed (D) chemotherapy in symptomatically stable patients: the MED trial.

BACKGROUND: Prior phase II trials have demonstrated the therapeutic activity of cytotoxic chemotherapy in mesothelioma. Currently there are few randomised data assessing the role of chemotherapy versus best supportive care (BSC) in the management of patients with stable symptoms after control of any pleural effusion. A policy of observation is often adopted over initial use of chemotherapy. In this prospective randomised trial we assess the use of early versus delayed cytotoxic therapy. The study opened in 1998, and closed in view of a competing national study (MSO 1) in 2003. METHODS: Eligible patients had a performance status3 months and had stable symptoms for at least 4 weeks prior to randomisation. Patients were randomised to receive immediate chemotherapy or initial BSC with the addition of chemotherapy at time of symptomatic progression. All patients received the same platinum-based chemotherapy regimen, MVP [mitomycin C 8 mg/m2 cycles 1, 2, 4 and 6, vinblastine 6 mg/m2, maximum 10 mg, and cisplatin 50 mg/m2 (or carboplatin AUC 5)], every 3 weeks for up to six cycles. RESULTS: A total of 43 patients were recruited, of which 21 were randomised to the early treatment group and 22 to the delayed treatment group. The median ages were 59 years (range 50-78) and 67 years (range 48-75), respectively (P=0.1); other baseline parameters were well matched between the two groups. All 21 patients in the early group received chemotherapy versus 17 patients in the delayed group. Median time to symptomatic progression was 25 weeks in the early group compared with 11 weeks for the delayed group (P=0.1). Median survival was 14 months (1-year survival 66%) for the early group compared with 10 months (1-year survival 36%) for the delayed group (P=0.1). Quality of life was in general better maintained for early treatment and the health resources use was similar in both arms. CONCLUSIONS: In this patient group, presenting with stable symptoms after control of pleural effusion, the early use of chemotherapy provided an extended period of symptom control, and in this small trial a trend to survival advantage.

[The effect of multimodality induction therapy for locally advanced non-small cell lung cancer].

In this study we analyzed induction therapy for locally advanced non-small cell lung cancer. Eligible patients had mediastinoscopic proven N2 disease and T4 with mediastinal involvement. From January 1997 to May 2005, 56 patients entered the study. They received 2 cycle chemotherapy (platinums based 2 or 3 drugs), in 32 patients with concurrent radiotherapy followed by surgery. Response rates were 57.1%. Fifty-one patients underwent surgery. A radical resection was possible in 39 patients. Complication occurred in 14 patients (27.5%). Overall 5-year survival was 27.5%. In N2 disease, there was no statistically significant difference in survival between the induction group and the historical group. In T4 disease, overall 5-year survival was 30.2% for the induction group and 5.2% for historical group. There was significant difference in survival between the groups (p < 0.05).

[Intraperitoneal chemotherapy in gastric cancer patients with peritoneal dissemination].

Peritoneal dissemination is one of the non-curative factors in gastric cancer and colon cancer. Although many treatments have been conducted for peritoneal dissemination, no standard chemotherapy has yet been established. For sometime we had used continuous hyperthermic peritoneal perfusion (CHPP)for peritoneal dissemination in gastric cancer and colon cancer. CHPP has a marked survival benefit for scirrhous type gastric cancer patients without liver metastasis. Patients with prophylactic CHPP have significantly better prognoses than those without prophylactic CHPP, and therapeutic CHPP has a survival benefit for gastric cancer patients with slight to moderate peritoneal dissemination (P 1-2). But CHPP has no significant prognostic benefit for gastric cancer patients with severe peritoneal dissemination (P 3). Therefore, a new cancer treatment is needed for those patients. On the other hand, many kinds of anticancer agents, including cisplatin, via intraperitoneal (ip) administration have been tried thus far for peritoneal dissemination therapy. Especially, intraperitoneal taxane anticancer agent is very effective for the treatment and local control of severe peritoneal dissemination in gastric cancer. A phase I/II study of taxane anticancer agents via ip administration should be tried in gastric cancer patients with peritoneal dissemination.

Platinum-based chemotherapy in metastatic breast cancer: the Leicester (U.K.) experience.

AIMS: After failure of anthracycline- and taxane-based chemotherapy in metastatic breast cancer, treatment options until recently were limited. Until the introduction of capecitabine and vinorelbine, no standard regimen was available. We conducted a retrospective study to determine the efficacy and toxicity of platinum-based chemotherapy in metastatic breast cancer. MATERIALS AND METHODS: Forty-two women with metastatic breast cancer previously treated with anthracyclines (93%) and/or taxanes (36%) received mitomycin-vinblastine-cisplatin (MVP) (n=23), or cisplatin-etoposide (PE) (n=19), as first-, second- and third-line treatment at a tertiary referral centre between 1997 and 2002. Chemotherapy was given every 3 weeks as follows: mitomycin-C (8 mg/m2) (cycles 1, 2, 4, 6), vinblastine (6 mg/m2), and cisplatin (50 mg/m2) all on day 1; and cisplatin (75 mg/m2) and etoposide (100 mg/m ) on day 1 and (100 mg/m2) orally twice a day on days 2-3. RESULTS: The response rate for 40 evaluable patients (MVP: n=23; PE: n=17) was 18% (95% confidence interval [CI]: 9-32%). The response rate to MVP was 13% (95% CI: 5-32%, one complete and two partial responses) and to PE 24% (10-47%, four partial responses). Disease stabilised in 43% (26-63%) and 47% (26-69%) of women treated with MVP and PE, respectively. After a median follow-up of 18 months, 37 women (MVP: n=19; PE: n=18) died from their disease. Median (range) progression-free survival and overall survival were 6 months (0.4-18.7) and 9.9 months (1.3-40.8), respectively. Median progression-free survival for the MVP and PE groups was 5.5 and 6.2 months (Log-rank, P = 0.82), and median overall survival was 10.2 and 9.4 months (Log-rank, P = 0.46), respectively. The main toxicity was myelosuppression. Grades 3-4 neutropenia was more common in women treated with PE than in women treated with MVP (74% vs 30%; P = 0.012), but the incidence of neutropenic sepsis, relative to the number of chemotherapy cycles, was low (7% overall). The toxicity-related hospitalisation rate was 1.2 admissions per six cycles of chemotherapy. No treatment-related deaths occurred. MVP and PE chemotherapy have modest activity and are safe in women with metastatic breast cancer.

[Clinical study on treatment of advanced stage non-small cell lung cancer by guben xiaoliu capsule].

OBJECTIVE: To observe the therapeutic effect of Guben Xiaoliu Capsule (GXC) in treating advanced stage non-small cell lung cancer (NSCLC). METHODS: One hundred and ninety-eight NSCLC in-patients were divided into the integrative treated group [Group A, 54 patients treated with chemotherapy (CT) plus GXC], the TCM treated group (Group B, 96 patients treated with GXC alone) and the chemotherapeutic group (Group C, 48 patients treated with CT alone). Randomized controlled observation was applied to the Group A and C. The clinical effect, quality of life (QOL), adverse reaction and survival period in the three groups were observed. RESULTS: The immediate effective rate (CR + PR) in the Group A, B and C was 16.7%, 3.1% and 8.3%, respectively, in the Group A, it was better than that in the other two groups (P < 0.05). The improvement of clinical symptoms and QOL in the Group A and B were superior to those in the Group C (P < 0.05). The median survival rate in the three groups was 12, 15 and 9 months, respectively, the 1-, 2- and 3-year survival rate in Group A being 57.4%, 11.1% and 3.7%, respectively, in Group B, 67.7%, 9.4% and 3.1%, and in (Group C, 39.6%, 4.2% and 0, respectively, comparison between the three groups showed that the survival rates in the former two were higher than those in Group C (P < 0.05). Moreover, the incidence rate and degree of CT toxicity were milder in Group A than those in Group C (P < 0.05). CONCLUSION: GXC has definite effect in treating NSCLC, it could raise the QOL, prolong the survival period of patients, also reduce the toxicity and enhance the efficacy of CT.

[Activity of toremifene plus mitomycin, vindesin and cisplatin regimen in unresectable non-small cell lung cancer].

OBJECTIVE: To investigate the activity and clinical efficacy of toremifene plus mitomycin, vindesin and cisplatin regimen (MVP) in non-small cell lung cancer (NSCLC). METHODS: A549 cells were seeded into 96 wells at the concentration of 10 x 10(4)cells/well and exposed to different agents. Seventy-two hours later, the cytotoxicity of the agents were evaluated with the method of MTT. The clinical trial included 63 patients with chemtherapy-naive NSCLC and 30 patients who had received chemotherapy (Pre-treatment arm). The chemotherapy-naive patients were randomly divided into the toremifene-treatment arm and the control arm. Each patient was given MVP chemotherapy. Five days before the chemotherapy, those in the toremifene-treatment group and pre-treatment arm started toremifene 420 mg daily orally for 7 days. The response was evaluated after two cycles of chemotherapy and toxic side effects and the survival of the patients were followed up. RESULTS: Toremifene decreased the IC(50) of chemotherapeutic agents and increased their cytotoxicity. In the clinical trial, the response rate and median survival were 47% and 11 months in the toremifene-treatment arm and 32% and 9 months in the control arm, respectively. The difference between the two arms was not significant. The response rate and median survival were 17% and 7 months in the pre-treatment arm, respectively. The toxicity among the three groups was not significantly different. CONCLUSIONS: Toremifene can improve the cytotoxicity of cisplatin, mitomycin and vindesin. Toremifene plus MVP regimen is safe and effective in the treatment of NSCLC.

Malignant mesothelioma--the UK experience.

In Britain it is estimated that the annual number of mesothelioma deaths will rise from approximately 1500 in the year 2000 to a peak of approximately 3000 in 2020. A database on the natural history of mesothelioma has provided a baseline for a new trial at The Royal Marsden looking at early versus delayed chemotherapy in mesothelioma as a new approach to treatment. In the UK chemotherapy is usually in the form of MVP (mitomycin, vinblastine and cisplatin) or vinorelbine, and data have been collected from trials covering both regimens. There is now a national working group for mesothelioma (BMIG) and a proposal for a national trial is being taken forward, comparing chemotherapy with MVP or single agent vinorelbine in addition to active symptom control (ASC) with ASC alone. Novel agents are also being investigated and SRL172 has shown some benefits in combination with chemotherapy in the treatment of malignant mesothelioma.

An update on choanal atresia surgery at Great Ormond Street Hospital for Children: preliminary results with Mitomycin C and the KTP laser.

We present the results of transnasal choanal atresia correction in 46 children, as an update to the published Great Ormond Street Hospital series. Females outnumbered males 2-1, and half the cases in our series were bilateral. Eight of the children with bilateral atresia had the CHARGE association. The median number of procedures required was three over a period of up to 3 years. Eighty-two percent of children with unilateral atresia and 78% of those with bilateral atresia were asymptomatic at the time of their last follow up. Four deaths occurred, all but one in children with CHARGE association. We were not able to demonstrate any benefit from the use of Mitomycin C, the KTP laser, betamethasone nasal drops or (in unilateral cases) stents.

High body mass index correlates with increased risk of venous irritation by vinorelbine infusion.

BACKGROUND: Vinorelbine is currently one of the most active chemotherapeutic agents. However, it is also a moderate vesicant that is well known to cause venous irritation and phlebitis. We conducted this study to identify clinical risk factors related to the incidence of venous irritation caused by peripheral vinorelbine infusion. METHODS: Medical records were used to investigate retrospectively a total of 201 cases of non-small cell lung cancer treated with a chemotherapeutic regimen containing vinorelbine. Venous irritation was evaluated in every course and graded according to the National Cancer Institute Common Toxicity Criteria version 2.0. Gender, age, body mass index (BMI), chemotherapeutic regimen, dose of vinorelbine and prior chemotherapy were used as clinical variables. RESULTS: A total of 928 vinorelbine infusions were administered to the 201 patients, among whom venous irritation occurred in 63 (31%). The incidence of venous irritation was 28% in the normal BMI (<25) group and 45% in the high BMI (25 or more) group and the difference between the two groups was statistically significant (P = 0.037). There were no significant correlations between the incidence of venous irritation and the clinical variables except BMI. In the multivariate analysis BMI was also a significant independent variable that correlated with increased risk of venous irritation (P = 0.017). CONCLUSIONS: Care is required when using vinorelbine to treat patients with a high BMI, especially with regard to the development of venous irritation.

BTS randomised feasibility study of active symptom control with or without chemotherapy in malignant pleural mesothelioma: ISRCTN 54469112.

BACKGROUND: The incidence of mesothelioma is rising rapidly in the UK. There is no generally accepted standard treatment. The BTS recommends active symptom control (ASC). It is not known whether chemotherapy in addition prolongs survival or provides worthwhile palliation with acceptable toxicity. Palliation as recorded by patients has been fully reported for only two regimens: mitomycin, vinblastine, and cisplatin (MVP), and vinorelbine (N). The BTS and collaborators planned to conduct a phase III randomised trial comparing ASC only, ASC+MVP, and ASC+N in 840 patients with survival as the primary outcome measure. The aim of the present study was to assess the acceptability of the trial design to patients and the suitability of two standard quality of life (QL) questionnaires for mesothelioma. METHODS: Collaborating centres registered all new patients with mesothelioma. Those eligible and giving informed consent completed EORTC QLQ-C30+LC13 and FACT-L QL questionnaires and were randomised between all three or any two of (1) ASC only, (2) ASC+4 cycles of MVP, and (3) ASC+12 weekly doses of N. RESULTS: During 1 year, 242 patients were registered of whom 109 (45%) were randomised (55% of the 197 eligible patients). Fifty two patients from 20 centres were randomised to an option including ASC only. This translates into a rate of 312 per year from 60 centres interested in collaborating in the phase III trial. The EORTC QL questionnaire was superior to FACT-L in terms of completeness of data and patient preference. Clinically relevant palliation was achieved with ASC. CONCLUSION: The planned phase III trial is feasible.

Isolated chemotherapeutic perfusion of the pelvis for advanced rectal cancer.

OBJECTIVE: Isolated pelvic perfusion exposes tissue to high doses of drug without the toxicity of high-dose systemic therapy and may benefit patients with advanced malignancy. PATIENTS AND METHODS: There were 32 patients with locally advanced, previously irradiated cancer of the rectum and 5 patients with anal canal cancer. These patients underwent a total of 65 isolated pelvic perfusions using 5-Fu (1500 mg/m2) for 60 min; cisplatinum (100 mg/m2) and mitomycin (10-20 mg/m2) were added to some perfusions. Hospital stay averaged 3-5 days. RESULTS: Palliative perfusion in 15 patients with advanced rectal cancer resulted in symptomatic relief from 1 to 4 months in 11 of 14 with pelvic pain and limited benefit in 6 patients with mass, but no pain. Pre-operative perfusion in 16 rectal cancer patients achieved a complete response (no tumour in pelvis) in 1 patient and significant tumour regression in 8 patients rendering them potentially resectable. Five were resected with clear margins. Three patients with recurrent epidermoid cancer had significant tumour regression and were resected with clear margins. CONCLUSION: Isolated chemotherapeutic perfusion of the pelvis provides excellent palliation for patients with advanced or pelvic recurrence of rectal cancer or epidermoid cancer of anorectum and may potentiate resection in selected patients.

[Perianal Bowen's disease: a case report and review of the literature]. / Perianal Bowen's disease: a case report and review of the literature.

Perianal Bowen's disease is a uncommon, slow growing, intraepidermal squamous-cell carcinoma (carcinoma in situ) of the anal region and may be a precursor to squamous carcinoma of the anus. It is associated with cervical and vulvar intraepithelial neoplasia and have human papillomavirus as a common cause. Both sexes and all races are affected, with the highest prevalence in patients aged 20 to 45 years. The symptoms of anal Bowen's disease are unspecific and the clinical findings are uncharacteristic and include pain, itching, bleeding and a disturbing lump. Biopsy and histopathologic examination is required for diagnosis and to distinguish other perianal dermatoses; thus an anogenital warts that fail to respond to conventional therapy, or change in appearance, warrant a biopsy and, where the technique is available, DNA typing to identify the viral pathogen. Infact the etiologic agent, the human papillomavirus (HPV), has been classified by DNA techniques into at least 42 types, of which 16 and 18 are considered to carry a high risk for cancer. The intraoperative findings is a lesion at the anocutaneous line: perianal or intra-anal tumor, erosion or ulceration as well as lichenoid lesion or hyperpigmentation. The disease has a proclivity for recurrence and there are many controversies concerning treatment that effectiveness remains uncertain and range from aggressive wide local excision with skin grafting when necessary to laser vaporization (argon or CO2), radiotherapy or a new immune response modifier (Imiquimod). We report a case of a 50-years-old woman with recurrence of Bowen's disease associated with vulvar HPV infection and review the literature.

A phase II study of mitomycin C, cisplatin and protracted infusional 5-fluorouracil in advanced pancreatic carcinoma: efficacy and low toxicity.

BACKGROUND: The effective treatment of unresectable pancreatic carcinoma represents a formidable challenge. There is a need to develop systemic therapies which combine efficacy with acceptable toxicity. The current 'gold standard' gemcitabine gives an objective response rate of the order of 20% and median survival up to 6 months. Here we have evaluated the efficacy and toxicity of mitomycin C, cisplatin and protracted infusional 5-fluorouracil (MCF). PATIENTS AND METHODS: Forty-five patients with locally advanced (13 patients) or metastatic (32 patients) pancreatic carcinoma were treated with mitomycin C 7 mg/m(2) 6 weekly, cisplatin 60 mg/m(2) 3 weekly and protracted venous infusion 5-FU 300 mg/m(2)/day. Patients were evaluated for response after three cycles and received six cycles in total in the absence of progressive disease or poor tolerance. Median age was 62 (45-75) years; 41 patients were World Health Organization performance status 0-1. RESULTS: Treatment was well tolerated with 36 (84%) patients completing three or more cycles. Grade 3 or 4 toxicities were uncommon: anaemia in three patients (7%), mucositis in two (5%), nausea and vomiting in three (7%) and diarrhoea in one (1%). An objective response was seen in 21 (46%) patients. There was one complete response. The median survival overall was 7.1 months and 10.5 months in responders. The median duration of response was 4.3 months. One-year survival was 29%, 2-year survival was 18%. CONCLUSIONS: MCF combines efficacy with low toxicity in the treatment of advanced pancreatic carcinoma. The efficacy is at least comparable and may be superior to single-agent gemcitabine and MCF may therefore provide a cost-effective alternative.