Smoking cessation in elective surgical patients offered free nicotine patches at listing: a pilot study.

Free nicotine patches may promote pre-operative smoking cessation. Smokers (≥ 10 cigarettes.day-1 ) awaiting non-urgent surgery were randomly assigned (3:1) to an offer of free nicotine patches or a control group who were not offered free nicotine patches. The suggested regimen lasted 5 weeks, with patch strength decreasing incrementally after 3 and 4 weeks. The primary outcome was smoking abstinence for ≥ 4 weeks, as self-reported by participants on the day of surgery, including, where possible, corroboration using exhaled carbon monoxide testing. Out of 600 included smokers, 447 (74.5%) were randomly assigned to an offer of pre-operative nicotine patches, with 175 (39.1%) of these accepting the offer and 56 (12.5%) using patches for ≥ 3 weeks. Out of 396 participants offered nicotine patches who were included for analysis, 36 (9.1%) quit smoking for ≥ 4 weeks before surgery as compared with 8 (5.9%) controls, OR 1.5 [95%CI 0.7-3.2], p = 0.300. Sixty-three (15.9%) quit smoking for 24 h before surgery as compared with 15 (11.1%) controls, OR 1.4 [95%CI 0.8-2.4], p = 0.200. Participants offered nicotine patches were more likely to engage in a cessation attempt lasting more than 24 h, 46 (11.6%) vs. 5 (3.7%), OR 3.4 [95%CI 1.8-8.8], p = 0.010. Out of 78 participants who quit smoking by the day of surgery and were followed up at 6 months, 46 (59%) had relapsed. Offering free nicotine patches stimulated interest in quitting compared with controls, but our protocol had limited effectiveness.

Loss of Fas apoptosis inhibitory molecule leads to spontaneous obesity and hepatosteatosis.

Altered hepatic lipogenesis is associated with metabolic diseases such as obesity and hepatosteatosis. Insulin resistance and compensatory hyperinsulinaemia are key drivers of these metabolic imbalances. Fas apoptosis inhibitory molecule (FAIM), a ubiquitously expressed antiapoptotic protein, functions as a mediator of Akt signalling. Since Akt acts at a nodal point in insulin signalling, we hypothesize that FAIM may be involved in energy metabolism. In the current study, C57BL/6 wild-type (WT) and FAIM-knockout (FAIM-KO) male mice were fed with normal chow diet and body weight changes were monitored. Energy expenditure, substrate utilization and physical activities were analysed using a metabolic cage. Liver, pancreas and adipose tissue were subjected to histological examination. Serum glucose and insulin levels and lipid profiles were determined by biochemical assays. Changes in components of the insulin signalling pathway in FAIM-KO mice were examined by immunoblots. We found that FAIM-KO mice developed spontaneous non-hyperphagic obesity accompanied by hepatosteatosis, adipocyte hypertrophy, dyslipidaemia, hyperglycaemia and hyperinsulinaemia. In FAIM-KO liver, lipogenesis was elevated as indicated by increased fatty acid synthesis and SREBP-1 and SREBP-2 activation. Notably, protein expression of insulin receptor beta was markedly reduced in insulin target organs of FAIM-KO mice. Akt phosphorylation was also lower in FAIM-KO liver and adipose tissue as compared with WT controls. In addition, phosphorylation of insulin receptor substrate-1 and Akt2 in response to insulin treatment in isolated FAIM-KO hepatocytes was also markedly attenuated. Altogether, our data indicate that FAIM is a novel regulator of insulin signalling and plays an essential role in energy homoeostasis. These findings may shed light on the pathogenesis of obesity and hepatosteatosis.

[Prevalence of protein-energy undernutrition evaluated by the measurement of triceps skinfold thickness and mid-arm muscle circumference of 103 adults with cirrhosis of the liver hospitalized in the department of hepatology and gastroenterology of the Lomé Campus University Hospital (Togo)]. / Prévalence de la dénutrition protéinoénergétique par la mesure du pli cutané tricipital et de la circonférence musculaire brachiale, chez 103 cirrhotiques adultes hospitalisés en hépato-gastro-entérologie au CHU Campus de Lomé (Togo).

OBJECTIVE: To evaluate by a reliable method the protein-energy nutritional status of adults hospitalized in the hepatology and gastroenterology department of the Lomé Campus University Hospital. METHODS: This cross-sectional prospective study conducted from March 1 to September 15, 2012, included 103 inpatients aged at least 16 years. The variables evaluated were: triceps skinfold thickness (TST), mid-arm muscle circumference (MAMC), serum albumin, CRP, and orosomucoid. The Child-Pugh classification was used to evaluate the clinical severity of liver disease. RESULTS: Within this population of patients with cirrhosis, 40 were alcohol-dependent (39.0%) and 85 had anorexia (82.5%); 49 were in group B of the Child-Pugh classification, and 37 in group C. We found a non-significant (p = 0.324) difference in TST measurement between the three Child-Pugh groups: A (8.4 ± 4.5); B (6.1 ± 3.7); and C (6.4 ± 7.2). The prevalence of protein-energy malnutrition ranged from 52.0% to 82.5%, when evaluated by MAMC or TST. Our results confirm the need to pay additional attention to the protein-energy nutritional status of inpatients in this department, by adding reliable tools, such as the TST and MAMC, to the biochemistry analysis to characterize undernutrition.

Adjuvant sequential chemotherapy and radiotherapy in uterine papillary serous carcinoma.

PURPOSE: To evaluate the efficacy and toxicity of adjuvant combination of sequential chemotherapy followed by radiotherapy in uterine papillary serous carcinoma (UPSC). METHODS AND MATERIALS: From April 1994 to June 2003, 26 patients (median age 61.7 years, range 46.9-78.4) with UPSC were treated with a platinum-based chemoradiation protocol after definitive surgery. 9 patients were assigned as stage I (35%), 4 were stage II (15%), 11 were stage III (42%), and 2 were stage IV (8%) according to the FIGO staging for gynecological cancers. All patients underwent total hysterectomy, salpingo-oophorectomy, pelvic +/- perioartic lymph nodes dissection/sampling, omentectomy, and peritoneal washing. The adjuvant chemoradiation protocol consists of 4 cycles of platinum-based chemotherapy followed by pelvic irradiation and vaginal vault brachytherapy. In selected stage I patients with no or minimal myometrial invasion, only vault brachytherapy was given after adjuvant chemotherapy. RESULTS: After a median follow-up of 28 months (range 9-113 months), 14 (54%) patients were alive and free of disease. 12 out of these 14 patients were FIGO stage I/II. 9 patients (35%) had died (8 from distant metastases). The Kaplan-Meier 2-year and 5-year survival estimates were 69.5% and 57%, respectively. Only 4 (15%) patients had pelvic recurrence. None of the patients developed local vault recurrence. The treatment was well tolerated, only 1 patient developed congestive cardiac failure from the chemotherapy and 6 patients had grade 2 peripheral neuropathy on follow-up. CONCLUSION: In our series of UPSC patients treated with adjuvant chemotherapy followed by radiotherapy, local control can be achieved in a majority of patients. Distant failure remains the major cause of mortality. Further investigations into finding a more effective systemic therapy are required if improvement in outcome for this form of uterine cancer is to be achieved.

Validity and reliability of the Chinese (Singapore) version of the Parkinson's Disease Questionnaire (PDQ-39).

OBJECTIVE: The purpose of the study was to validate the Chinese (Singapore) version of the Parkinson's Disease Questionnaire (PDQ-39CSV) and its briefer version (PDQ-8CSV). METHODS: A convenience sample of Chinese-speaking Singaporeans with Parkinson's disease (PD) (n = 63) completed a questionnaire containing the PDQ-39CSV and the Chinese (Singapore) EQ-5D. A subgroup also participated in a retest and/or a focus group discussion. A priori hypotheses were tested by examining correlations between PDQ-39CSV, PDQ-8CSV and EQ-5D scores and using principal component factor analysis. Reliability was assessed using Cronbach's alpha and intra-class correlation coefficients (ICC). RESULTS: Thirty-two PDQ-39CSV items correlated satisfactorily with their hypothesized dimensions (Spearman's p > or = 0.4). Factor analysis yielded a component on which all 8 PDQ-39CSV dimensions were substantially loaded (loading range: 0.53-0.89). As hypothesized, the PDQ-39CSV and PDQ-8CSV summary indices were highly correlated (Pearson's r:0.95, ICC:0.94); correlations between related PDQ and EQ-5D scores were generally strong (Spearman's p: 0.38-0.76, p < 0.001 for all). Cronbach's alpha values ranged from 0.64 to 0.90 and ICC values from 0.66 to 0.86. CONCLUSION: This study provides preliminary evidence supporting validity and reliability of both the PDQ-39CSV and its briefer version.

The relevance of oncogenes as prognostic markers in cervical cancer.

To study the prevalence of the oncogenes c-myc, IFN-alpha; c-erbB2; H-ras codon 12, 13, and 61; c-fos; and E6/E7 oncogenes of human papillomavirus (HPV) 16 in patients with invasive carcinoma of the cervix and their prognostic significance, genomic DNA and RNA were isolated from tissues of 275 patients in Singapore with nonmetastatic cervical cancer and 32 patients with normal cervix. The levels of expression of the various oncogenes were quantified by PCR using the respective primers. When the PCR data on the DNA were analyzed by the log-rank test, IFN gamma (P = 0.02) and H-ras codon 12 and 13 (P = 0.02) were found to be prognostic. In the multivariate analysis, a statistically significant trend for increasing risk with higher quartiles was found for c-myc (P = 0.007) and c-erbB2 (P = 0.03). After adjusting for age and stage, a correlation appears between the amplification of the oncogenes c-myc, c-erbB2, and H-ras codon 12, 13, and 61 and the development of recurrent cervical cancer. Further adjustment to include the parameters of treatment and histology type did not change the outcome of the correlation observed.

Phase II trial and pharmacokinetic evaluation of cytosine arabinoside for leptomeningeal metastases from breast cancer.

PURPOSE: To determine the efficacy and pharmacokinetics of intraventricular cytosine arabinoside (Ara-C) as front-line treatment for leptomeningeal metastases from breast cancer. METHODS: Ten patients newly diagnosed with leptomeningeal metastases (LMM) from breast cancer were treated with 100 mg intraventricular cytosine arabinoside (IVT Ara-C) via an Ommaya reservoir. Treatment was administered three times a week for 2 weeks, then once a week for 4 weeks, and then once every 6 weeks for four cycles to responding patients. Nine patients were evaluable clinically, and seven patients underwent testing to determine the pharmacokinetic profile of Ara-C in the cerebrospinal fluid (CSF). RESULTS: Two patients had partial responses lasting 9 and 40 weeks, respectively. Two other patients had stable disease. The median survival duration was 30 weeks (range: 5-58 weeks). Seven patients died from LMM. Acute toxic effects associated with IVT Ara-C included meningismus, nausea, vomiting, and myelosuppression. The median peak Ara-C level in CSF was 16.69+/-6.30 mM (SD). The half life for elimination was 1.45+/-0.61 h (SD) There was no drug accumulation between courses. Neuropsychological evaluations were completed in eight patients, six (75%) of whom had preexisting cognitive deficits. Their condition generally improved over the course of treatment until the LMM progressed. No neurotoxic side effects of IVT Ara-C were observed in the two patients who had normal baseline cognitive assessments. CONCLUSIONS: IVT Ara-C at this dose and schedule has minimal activity as initial treatment for LMM from breast cancer despite achievement of high peak levels of the drug in the cerebrospinal fluid. A liposomal Ara-C formulation is currently under investigation.

Separating touching objects in remote sensing imagery: the restricted growing concept and implementations.

This paper defines the restricted growing concept (RGC) fur object separation and provides an algorithmic analysis of its implementations. Our concept decomposes the problem of object separation into two stages. First, separation is achieved by shrinking the objects to their cores while keeping track of their originals as masks. Then the core is grown within the masks obeying the guidelines of a restricted growing algorithm. In this paper, we apply RGC to the remote sensing domain, particularly the synthetic aperture radar (SAR) sea ice images.

Uterine leiomyosarcoma--a Singapore experience.

Uterine leiomyosarcoma is an aggressive tumour. In our retrospective series of 27 patients, there were 25 with nonmyxoid high-grade leiomyosarcoma of the uterus. The stage distribution was Stage 1, 16; Stage 3, 5 and Stage 4, 4. In the patients with Stage 1 disease, 3 of the 8 patients who received adjuvant chemotherapy subsequently developed recurrent disease. In contrast, 6 of the 8 patients who did not receive adjuvant chemotherapy subsequently developed recurrent disease; 2 of the patients in the latter group also received adjuvant radiotherapy. Six of the 9 women with recurrences were distant 'failures' alone, 2 were both distant and pelvic 'failures' and 1 was pelvic 'failure' alone. All the patients with advanced-stage disease eventually succumbed to the disease despite the therapies given. This study is small and retrospective but it suggests that there might be a role for adjuvant chemotherapy in the management of the early stage of this disease.

Mitomycin, ifosfamide and cisplatin in advanced non-small cell lung cancer.

BACKGROUND: Chemotherapy can be used to palliate the symptoms in patients with advanced non-small cell lung cancer. PATIENTS: Twenty-four chemo-naive patients with stage IIIB and IV non-small cell lung cancer were treated with the MIC regimen (mitomycin, ifosfamide and cisplatin). RESULTS: The overall response rate was 33% (partial response) and median duration of response was 7 months (range 5 to 10 months). At median follow-up of 26 months, the median survival was 8 months, and 1-year survival was 29%. Toxicities were tolerable. CONCLUSION: This appears to be a reasonable regimen for palliating advanced non-small cell lung cancer.

Treatment of small cell lung cancer: a single institutional experience.

Forty-three patients with either limited or extensive small cell lung carcinoma were treated with either etoposide and cisplatin (EP) regimen or EP alternating with cyclophosphamide, doxorubicin and vincristine. Patients with limited disease were consolidated with radiotherapy. Responses were 96% (44% complete response) and 71% (6% complete response) in the patients with limited and extensive diseases, respectively. The 2-year disease-free and overall survival in the limited disease patients were 19% and 27%, respectively. None of the patients with extensive disease survived beyond 2 years. Toxicity of the therapy was acceptable. Forty percent developed grade 2 vomiting. Two patients had neutropenic fever of which one was fatal. One of the two-year survivors developed a second malignancy (oesophageal carcinoma). Despite consolidative radiotherapy in all responding patients with limited disease, 73% of the failure included a locoregional component. In the entire group, one-third of the patients developed brain metastases. Hence, more effective drugs and local treatment modalities are needed to improve this result.

Primary mediastinal germ cell tumour.

Testicular germ cell tumour is said to be a model for curable neoplasm. However, the prognosis of primary extragonadal germ cell tumour does not appear to be as promising. Though similar in histology, the biology of primary extragonadal germ cell tumour is different as exemplified by the patients in this review. Eight patients with primary mediastinal germ cell tumours were treated with intensive cisplatin-based chemotherapy. All, except one, had non-seminomatous components. The poor prognosis of mediastinal germ cell tumour is due to a combination of poor treatment results with the cisplatin-based regimen and the development of non-germ cell and haematological malignancies.

Phase II trial of docetaxel (Taxotere) in metastatic colorectal carcinoma.

BACKGROUND: Docetaxel (Taxotere) is prepared from a noncytotoxic precursor extracted from the needles of the Taxus baccata. Preclinical investigations have demonstrated that docetaxel is very active in colon adenocarcinoma murine models. Phase I studies revealed granulocytopenia to be the dose-limiting toxicity. Initial clinical trials also demonstrated docetaxel's activity in ovarian, breast, and non-small cell lung cancer. Because of this encouraging preclinical and clinical activity, we initiated a phase II study of docetaxel in patients with metastatic colorectal carcinoma. PATIENTS AND METHODS: Docetaxel, 100 mg/m2, was administered as a 1-hour intravenous infusion every 21 days. Nineteen patients were entered on the trial. All patients had measurable disease and had not received prior chemotherapy for metastatic disease. RESULTS: No complete or partial responses were observed. Granulocytopenia was the dose-limiting toxic effect. Seventeen patients had grade 4 granulocytopenia; 8 of these patients received antibiotics for neutropenic fevers. Twelve patients experienced hypersensitivity reactions, and 15 patients experienced cutaneous toxic reactions. One patient demonstrated evidence of fluid retention. CONCLUSIONS: Administered at the stated dose and schedule, docetaxel has little activity against metastatic colorectal carcinomas. The toxicity profile, consisting of granulocytopenia, hypersensitivity reactions, cutaneous reactions, and edema, has been previously described in patients receiving docetaxel.

Use of oral and intravenous ondansetron in patients treated with cisplatin.

Ondansetron, a selective 5-HT3 antagonist, has been shown to be effective in preventing chemotherapy-induced nausea and vomiting. From July and August 1991, 25 patients were accrued in a phase II study to assess the efficacy of ondansetron in patients receiving cisplatin-containing chemotherapy. Patients received intravenous cisplatin 100 mg/m2, given either as a 24-hour infusion on day 1 or in divided doses as eight-hour infusions daily on days 1 to 3. Each patient received 24 mg of ondansetron per day for six days. Intravenous dexamethasone 24 mg was given daily on the days of cisplatin infusion. The emetic episodes and degree of nausea were evaluated daily. "Good" control of emesis (0-2 episodes of vomiting) and nausea (mild or no nausea) ranged from 64-100% and 88-100% respectively. Failure in emesis control occurred most frequently on days 3 and 4. Ondansetron was generally well tolerated with only minimal side-effects. One patient developed unexplained encephalopathy which resolved completely. Our results suggest that ondansetron is an effective anti-emetic agent with minimal toxicities. Randomised studies comparing ondansetron against "standard" anti-emetics should be conducted.

MACOP-B in advanced non-Hodgkin's lymphoma.

Between May 1986 and March 1991, 38 patients with previously untreated advanced intermediate and high-grade non-Hodgkin's lymphoma were treated with methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B): 73% of the patients had stages III and IV disease, 55% had "B" symptoms, and 55% had bulky disease (nodal masses > 10 cm). Histologic subtypes included diffuse large-cell and immunoblastic lymphoma. In 96% of patients clinical response was achieved (69% complete response and 27% partial response). Acturial disease-free survival and overall survival were 55% and 60%, respectively, at 2 years. Treatment-related mortality was 16%: 3 patients died from neutropenic sepsis and 3 (hepatitis B carriers) from fulminant hepatitis at the time of steroid withdrawal. The incidence of nonfatal neutropenic fever was 24% and mucocutaneous toxicity was common. The poorer overall results may be attributed to more advanced disease. Caution is advised in the use of MACOP-B among hepatitis B carriers.

Implantable subcutaneous infusion ports.

Limited vascular access hinders administration of chemotherapy, blood products and antibiotics in cancer patients. Repeated venous cannulation is often psychologically traumatic to patients. The use of a subcutaneous infusion port allows convenient vascular access. Twenty-two cancer patients had ports implanted for venous access (17 patients) and administration of regional chemotherapy (5 patients). The period of indwelling ranged from 70 to 470 days (median 270 days). Two patients (9%) had wound dehiscence that required port revision. Despite this, the wound did not heal in 1 patient and the port had to be removed. Other complications included venous thrombosis (5%) and subcutaneous haematoma (5%). There was no catheter-related bacteraemia. The subcutaneous infusion port provides a suitable vascular access in cancer patients.

Adult parameningeal rhabdomyosarcoma--a case report and literature review.

Although rhabdomyosarcoma is predominantly a malignant disease of children, it is also seen in adults. Since adults account for only 15% of rhabdomyosarcomas, the experience gathered for the treatment of the malignancy has been derived from treating children. The treatment of a case of adult extensive parameningeal rhabdomyosarcoma with CyVADlC chemotherapy and radiotherapy is described, together with a review of the literature.

Combined chemotherapy using cisplatin, ifosfamide and bleomycin (PIB) in the treatment of advanced and recurrent cervical carcinoma.

Combined cisplatin, ifosfamide and bleomycin (PIB) chemotherapy was given to 14 (11 recurrent and 3 advanced and metastatic) cervical carcinoma patients. At least 2 cycles of chemotherapy were given before assessment of tumour response. The overall response rate was 28.6%; the complete response rate was 14.3%. Sites of response included cervical lymph nodes and the lung. Toxicity was common. Alopecia was universal. Other toxicity included suppression of haematopoiesis (73%), leucopenia (71%) and nausea and vomiting. Two patients died from sepsis during the myelosuppressive phase. The role of PIB in the management of advanced and recurrent carcinoma of the cervix should be evaluated in a randomized-controlled trial.

Embryonal carcinoma arising in Turner's syndrome.

Risk of malignant transformation in a dysgenetic gonad is high. This is a report of a 23 year-old female who presented with symptoms and signs of ovarian neoplasm which was histologically confirmed as embryonal carcinoma. She had features of Turner's syndrome and was found to have XO chromosomal constitution. Embryonal carcinoma arising in a dysgenetic gonad is uncommon. It is even rarer when it arises in a patient with pure 45 XO. The following is a case report which highlights the role of chemotherapy and surgery in the management. It includes a literature review on the clinical features, genetic variants and malignant transformation in dysgenetic gonad. The role of prophylactic removal of dysgenetic gonad is discussed.