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Biomedical subjects

S V Kane

Publications and source records attributed to S V Kane.

At least 19 recordsLinked to original sources

Depth of invasion is the most significant histological predictor of subclinical cervical lymph node metastasis in early squamous carcinomas of the oral cavity.

AIMS: Cervical node metastasis is the single most important prognostic factor in head and neck squamous carcinomas. Taking a homogenous patient population, applying stringent selection criteria, and standard pathological evaluation methods, this retrospective study aims to establish histological predictors of subclinical cervical node metastasis in early (T1-T2/N0) squamous carcinomas of the oral cavity, thereby identifying a subset of patients who are at an increased risk for cervical node metastasis. METHODS: Forty-eight previously untreated patients with clinically T1 or T2, and N0, squamous carcinomas of the oral cavity who were treated with primary excision of the tumour and elective neck node dissection were selected. Various histological factors including T size, gross and microscopic tumour depth and thickness, grade of differentiation, pattern of invasion, inflammatory response, perineural and lymphovascular invasion were studied. The statistical significance of various parameters as predictors of subclinical node metastasis was determined using logistic regression analysis. RESULTS: Of all the parameters studied, microscopic tumour depth and thickness were the only significant factors (P value=0.026 and 0.046, respectively) which correlated with cervical node metastasis, on univariate analysis. Tumour depth emerged as a single most significant predictor on multivariate analysis. Majority of patients with node metastasis had a tumour depth of more than or equal to 5 mm. CONCLUSION: Depth is the most significant predictor of cervical node metastasis in early squamous carcinomas of the oral cavity. Patients with a tumour depth of more than or equal to 5 mm are at an increased risk of harbouring node metastasis, hence should be taken up for elective node dissection.

Carcinoma, Squamous Cell↗

Systematic review: adherence issues in the treatment of ulcerative colitis.

Ulcerative colitis is a chronic inflammatory and debilitating disease requiring lifelong treatment. First-line therapy for ulcerative colitis is 5-aminosalicylic acid, which suffers from poor patient adherence outside the clinical trial setting. Formulations to deliver 5-aminosalicylic acid to the disease activity site, both orally and topically, are often inconvenient and require multiple daily dosing. Such regimens can interfere with normal life and reduce the overall quality of life, negatively impacting on treatment adherence and leading to poorer long-term outcomes. These include increased morbidity with an elevated risk of symptomatic relapse, possible greater risk of colorectal cancer and higher overall costs of care. Ulcerative colitis patients cite treatment regimen complexity, tablet quantity and dose frequency as key negative influencers of adherence. Solutions to these issues include addressing patient concerns, simplifying daily regimens and utilizing new formulations such as micropellet and multimatrix oral formulations, rectal gel and once-daily suppository formulations. This review examines the prevalence and impact of non-adherence to 5-aminosalicylic acid therapy among patients with ulcerative colitis, as well as drug delivery strategies that may enhance dosing regimens to improve patient acceptability, adherence and long-term clinical outcomes. It is a combination of understanding patient behaviour, recognizing signs of non-adherent behaviour and utilizing management strategies to change behaviour that will improve patient outcomes.

Administration, Oral↗

5-ASA and colorectal cancer chemoprevention in inflammatory bowel disease: can we afford to wait for 'best evidence'?

Patients with inflammatory bowel disease have a higher risk of developing colorectal cancer. The main risk factors for colorectal cancer are not suitable targets for therapeutic intervention, and primary chemoprevention is an intriguing therapeutic option. The analogies between acetyl-salicylic acid and 5-amino-salicylic acid, and the results obtained by using acetyl-salicylic acid as a chemopreventive agent in patients with sporadic colorectal cancer have prompted the study of potential chemopreventive effects of 5-amino-salicylic acid in inflammatory bowel disease. The results of both epidemiological and experimental studies have shown that long-term 5-amino-salicylic acid treatments appear to have a chemopreventive effect. The evidence for this effect is provided by retrospective and case-control studies whose results, however, do not reach the highest grades for evidence-based recommendations. Nevertheless, these results are supported by a series of experimental studies demonstrating the multiplicity of actions of 5-amino-salicylic acid. Although data regarding the chemopreventive effect of 5-amino-salicylic acid may not be rigorous enough to meet the criteria for the highest evidence-based medicine recommendations, we feel that the argument to wait until we have Grade A evidence is not necessarily rational in this case, because discontinuation of 5-amino-salicylic acid treatment to perform a randomised controlled trial would be unethical secondary to their proven efficacy for maintenance treatment.

Anti-Inflammatory Agents, Non-Steroidal↗

Systematic review: short-term adverse effects of 5-aminosalicylic acid agents in the treatment of ulcerative colitis.

AIM: To determine whether there is a difference in short-term adverse events in patients with ulcerative colitis treated with mesalazine, olsalazine or balsalazide. METHODS: MEDLINE was searched for articles published until 2002. Randomized trials of oral mesalazine, olsalazine or balsalazide for the treatment of active disease or the maintenance of remission were included. Outcomes of interest were the frequencies of patients experiencing adverse events and those withdrawn due to adverse events. RESULTS: Forty-six trials were included. One study of mesalazine vs. sulfasalazine for active colitis showed significantly fewer patients with adverse events with mesalazine. Both balsalazide vs. sulfasalazine studies for active disease showed significantly fewer withdrawals with balsalazide. One trial of balsalazide vs. sulfasalazine for maintenance showed significantly fewer patients with adverse events with balsalazide. Otherwise, no significant differences in safety outcomes were noted. CONCLUSION: All three 5-aminosalicylic acid agents are safe in the short term. In mesalazine-treated patients, the frequencies of adverse events or withdrawals due to adverse events were comparable with those in placebo-treated patients and lower than those in sulfasalazine-treated patients. Overall, adverse events or withdrawals were not significantly more frequent with olsalazine than with placebo or sulfasalazine. Adverse events and study withdrawals on balsalazide were less frequent than those on sulfasalazine.

Administration, Oral↗

The effectiveness of budesonide therapy for Crohn's disease.

AIM: To assess the effectiveness and safety of budesonide in comparison to corticosteroids, 5-aminosalicylic acid (5-ASA), or placebo for inducing remission of active Crohn's disease and for maintaining remission. STUDY SELECTION CRITERIA: Randomized controlled trials comparing budesonide to corticosteroids, 5-ASA products or placebo were included. Trials had to report on the effectiveness of treatment (defined as decreasing or maintaining Crohn's Disease Activity Index, CDAI, scores < or = 150) or adverse events. DATA ANALYSIS: After assessing the validity of study design and independent, duplicate data extraction from selected trials, summary relative risks (RR) were calculated for each outcome. A test of heterogeneity was also calculated for each outcome using a random effects model. RESULTS: Budesonide was more likely to induce remission than placebo (RR=1.82, 95% CI: 1.15-2.88) or 5-ASA (RR=1.73, 95% CI: 1.26-2.39), although only one trial compared budesonide to 5-ASA products. Although budesonide induced remission less frequently than conventional corticosteroids (RR=0.87, 95% CI: 0.76-0.995), there was no significant difference between conventional corticosteroids and budesonide for inducing remission among patients with a low disease activity (initial CDAI=200-300). Budesonide was significantly less likely to cause corticosteroid-associated adverse events than conventional corticosteroids (RR=0.65, 95% CI: 0.53-0.80). No significant difference in total adverse events or corticosteroid-associated adverse events was demonstrated between budesonide and 5-ASA or placebo. CONCLUSION: Budesonide is significantly more effective than placebo or 5-ASA for inducing remission of active Crohn's disease. Although budesonide is 13% less effective for the induction of remission in active Crohn's disease than conventional corticosteroids, it is less likely to cause corticosteroid-related adverse effects. Budesonide is ineffective in maintaining remission.

Anti-Inflammatory Agents↗

Prevalence of nonadherence with maintenance mesalamine in quiescent ulcerative colitis.

OBJECTIVE: There are scant data regarding outpatient adherence in quiescent ulcerative colitis aside from patients enrolled in controlled clinical trials. We conducted a prevalence study to determine the medication adherence rate of maintenance therapy and to identify possible risk factors for nonadherence. METHODS: Outpatients with clinically quiescent ulcerative colitis for >6 months on maintenance mesalamine (Asacol, Procter and Gamble, Cincinnati, OH) were eligible. Patients were interviewed regarding disease history, and demographics were obtained from medical records. Refill information for at least 6 months was obtained from computerized pharmacy records. Adherence was defined as at least 80% consumption of supply dispensed. Using nonadherence as the outcome of interest, stratified analysis and regression modeling were used to identify significant associations. RESULTS: Data were complete for the 94 patients recruited. The overall adherence rate was found to be 40%. The median amount of medication dispensed per patient was 71% (8-130%) of the prescribed regimen. Nonadherent patients were more likely to be male (67% vs 52%, p < 0.05), single (68% vs 53%, p = 0.04), and to have disease limited to the left side of the colon versus pancolitis (83% vs 51%, p < 0.01). Sixty-eight percent of patients who took more than four prescription medications were found to be nonadherent versus only 40% of those patients taking fewer medications (p = 0.05). Age, occupation, a family history of inflammatory bowel disease, length of remission, quality-of-life score, or method of recruitment (telephone interview vs clinical visit) were not associated with nonadherence. Logistic regression identified that a history of more than four prescriptions (odds ratio [OR] 2.5 [1.4-5.7]) and male gender (OR 2.06 [1.17-4.88]) increased the risk of nonadherence. Two statistically significant variables, which were protective against nonadherence, were endoscopy within the past 24 months (OR 0.96 [0.93-0.99]) and being married (OR 0.46 [0.39-0.57]). CONCLUSION: Nonadherence is associated with multiple concomitant medications, male gender, and single status. These patient characteristics may be helpful in targeting those patients at higher risk for nonadherence.

Adult↗

Novel therapies in the treatment of ulcerative colitis.

Ulcerative colitis is a chronic inflammatory disease of unknown cause. Its course is one of relapse and remission and requires therapy for both the induction and maintenance of remission. The progress in the fields of genetics and immunology has afforded important advances in our understanding of the inflammatory process. Traditional therapy with non-specific anti-inflammatories for ulcerative colitis remains our gold standard as newer targeted therapies have failed to provide any improved efficacy. This review examines the most recent compounds in development for the treatment of ulcerative colitis, including data from early clinical trials and the potential clinical impact of future entities.

Animals↗

Thalidomide therapy for patients with refractory Crohn's disease: an open-label trial.

BACKGROUND & AIMS: Inhibition of tumor necrosis factor is a proposed mechanism for the anti-inflammatory properties of thalidomide. We performed an open-label trial of thalidomide in refractory Crohn's disease. METHODS: Twenty-two patients with refractory Crohn's disease (Crohn's Disease Activity Index [CDAI] > 200 and/or draining perianal disease) initiated therapy with thalidomide, 200 mg at bedtime (18 patients), or 300 mg at bedtime (4 patients). CDAI and goal interval scores (GIS) were assessed at weeks 0, 4, and 12. Clinical response for patients with luminal disease was defined as reduction in CDAI score of >150 points and for fistula patients was 2 scores of >/=1+ in 3 parameters of the GIS. Clinical remission was defined as a total CDAI < 150 (luminal patients) or >/=2+ for all parameters of the GIS (fistula patients). RESULTS: Nine patients with luminal disease and 13 with fistulas (16 male, 6 female) were enrolled. The median CDAI score at entry was 371 (95-468). Sixteen patients completed 4 weeks of treatment (12 clinical responses, 4 clinical remissions). All 14 patients completing 12 weeks met criteria for clinical response. Nine achieved clinical remission (3 luminal, 6 fistula patients). The median CDAI score was 175 (30-468; P < 0.001 vs. baseline). CONCLUSIONS: Thalidomide is efficacious in some patients with refractory Crohn's disease.

Adult↗

Borderline epithelial tumours of the ovary--a retrospective analysis of 31 cases.

Thirty one cases of epithelial borderline tumours of the ovary recorded over a period of six years were reviewed. The incidence of borderline tumours was 6% in relation to ovarian epithelial malignancies, with serous and mucinous types comprising three fourth of the lesions. The serous tumours were bilateral in 39%, revealed surface growth in 17% and had peritoneal implants in 11% of cases. The mucinous tumours were bilateral in 11% and had associated pseudomyxoma peritonei in 22% of cases. Nuclear grade appeared to correlate with extraovarian spread and surface growth in the serous borderline tumours, but not in the mucinous borderline tumours. The endometrioid borderline tumours and mixed epithelial borderline tumours were rare lesions. Twenty one patients (68%) presented in Stage-la. Surface growth correlated with recurrences. The prognosis remained good in serous borderline tumours even in the presence of implants as these were non-invasive. The mean disease free survival was 43.03 months. There was no statistical difference in disease free survival of patients with and without implants.

Adenofibroma↗

The menstrual cycle and its effect on inflammatory bowel disease and irritable bowel syndrome: a prevalence study.

OBJECTIVE: Female patients with bowel disease commonly report worsening symptoms in relation to the menstrual cycle. Our aim was to determine the nature of gastrointestinal symptoms correlating with the menstrual cycle in women with inflammatory and irritable bowel disease. METHODS: This was a retrospective study involving 49 women with ulcerative colitis (UC), 49 women with Crohn's disease (CD), 46 women with irritable bowel syndrome (IBS), and 90 healthy community controls. Participants were interviewed using a questionnaire including information regarding general health, medication history, pregnancy, as well as premenstrual and menstrual symptoms. Chi2 testing and logistic regression modeling were used to test for differences in frequencies between groups and for risk analysis. RESULTS: Premenstrual symptoms were reported by 93% of all women but statistically more often by patients with CD (p < 0.01). CD patients were also more likely to report increased gastrointestinal symptoms during menstruation ( < 0.01), diarrhea being the symptom reported most often. All disease groups had a cyclical pattern to their bowel habits significantly more than controls (p=0.01). Cyclical symptoms included diarrhea, abdominal pain, and constipation. Logistic regression revealed an odds ratio (OR) of 1.1 (95% CI 0.9-1.2) for experiencing bowel symptoms during the premenstrual and menstrual phases and an OR of 2.0 (95% CI 1.2-3.2) for experiencing a cyclical pattern in bowel habit changes in women with bowel disease. CONCLUSION: The prevalence of menstrually related symptoms is high, and appears to affect bowel patterns. The physiological and clinical effects of the menstrual cycle should be taken into consideration when assessing for disease activity.

Adult↗

Management of hepatocellular carcinoma: staging and treatment.

Hepatocellular carcinoma (HCC) is a common malignancy worldwide. Viral hepatitis B and C and cirrhosis are the most important risk factors. The two most established methods of screening are ultrasound and alpha-fetoprotein serum levels followed serially. The intervals of testing and cost efficacy have not yet been established. When HCC is discovered staging is important in order to guide treatment. Assessment for portal vein patency by ultrasonography and dynamic CT are noninvasive and sensitive. Magnetic resonance imaging and lipiodol CT are also helpful. The treatment depends on the patient's clinical condition related to liver function and other comorbid conditions and the number, size, and location of the lesions. The roles of tumor resection, liver transplantation, percutaneous alcohol injection, transarterial chemoembolization, and systemic chemotherapy are dependent on staging. Careful selection of patients and combined treatment modalities may be the keys to improve survival.

Carcinoma, Hepatocellular↗

Primary carcinoid tumor of the liver: report of four resected cases including one with gastrin production.

Four cases of primary hepatic carcinoid were identified during a retrospective study of liver resections for primary tumor. The cases included two adult males, one adult female, and a 9-year-old boy in whom gastrin levels were documented. The estimation of gastrin levels was prompted by symptoms suggestive of acid-peptic disease. One patient died postoperatively. The other three are alive and well at 3 years, 2 years, and at 1 year, respectively, after surgery, outcomes distinctly different from hepatocellular carcinomas. Diagnostic difficulties may be experienced in histologic assessment, and this may require recourse to immunohistochemistry and electron microscopy. Long-term follow-up and careful exclusion of a possible primary elsewhere are necessary for establishing the primary nature of liver carcinoids.

Adult↗

Giant cell fibroblastoma.

A report of a 1 1/2-year-old male child diagnosed as a case of giant cell fibroblastoma is described and the available literature on this neoplasm is reviewed. The tumor consists of a mixture of spindle cells and multinucleated giant cells in a myxoid or collagenous background. The pathological findings and clinical course suggest that these tumors be classified with fibromatoses of childhood. Removal of the tumor with wide excision is sufficient and these patients do not require any form of chemotherapy.

Fibroma↗

Head and neck synovial sarcomas.

Eleven cases of synovial sarcoma of the head and neck are analyzed. Patients presented with a mass either in the parapharynx, pharyngeal wall, or nape of the neck. The tumors ranged in size from 3 to 8 cm. Microscopically, the classic biphasic pattern was seen in 10 tumors. Immunohistochemistry and electron microscopy were useful in the diagnosis of the single monophasic variant of synovial sarcoma. Radical surgery was the mainstay of treatment with post-operative radiotherapy for residual disease. Five patients were dead of disease while 6 were alive for periods varying from 9 months to 15 years. The purpose of this presentation is to accrue data on this sarcoma at a rare site, and to highlight the histopathological differential diagnosis, which includes both carcinomas and sarcomas. Treatment decisions would be affected by the histology report.

Adolescent↗

Lack of association between oral contraceptive use and ulcerative colitis.

Previous epidemiological studies suggesting an association between oral contraceptive use and ulcerative colitis incidence have been weak and conflicting. To measure a possible association, 46 incident cases of ulcerative colitis patients, women aged 18-50 years, were compared with peer-nominated age-matched and sex-matched controls. There were no differences between case and control patients in demographic characteristics. There was no association between oral contraceptive use and ulcerative colitis (current use: odds ratio 0.70, 95% confidence interval 0.27-1.83; former use: odds ratio 1.14, confidence interval 0.41-3.15; current or former use: odds ratio 0.86, confidence interval 0.40-1.85). Stratifying by disease location (pancolitis or left-sided disease) also failed to identify an association. Controlling for possible confounding effects of cigarette smoking did not alter the lack of association between oral contraceptive use and ulcerative colitis. Similarly, testing for interaction failed to demonstrate any effect modification. Analyzing for duration of current oral contraceptive use or time interval since last use failed to demonstrate a "dose-response" effect. The study was of sufficient size to detect statistical significance for oral contraceptive use for odds ratios of 2.8 and higher. In this matched case-control study of incident cases and community controls, there was no association between oral contraceptive use and ulcerative colitis incidence. To date, there is no evidence suggesting that women predisposed to the development of ulcerative colitis should be advised to avoid oral contraceptive use.

Adult↗

Colon cancer surveillance in chronic ulcerative colitis: historical cohort study.

Screening for dysplasia in ulcerative colitis is expected to improve cancer-related survival by advancing the diagnosis of cancer to a more favorable pathologic stage or by identifying patients for prophylactic colectomy who are at at high risk of developing cancer. To evaluate the effectiveness of a surveillance program of annual colonoscopy and mucosal sampling, 91 screened and 95 control ulcerative colitis patients with extensive disease for at least 8 yr were compared for differences in survival, cancer detection, and colectomy rates. The two groups were of similar age at symptom onset, duration of disease, and sex. In the surveillance group, there were eight fewer deaths (p less than 0.05 by survival-curve analysis), but two more cancer deaths (not significant). Colectomy was less common (p less than 0.05) and was performed 4 yr later in the surveillance group. The effect of surveillance was not confounded by age at symptom onset, sex, or duration of disease. In our program, screening for cancer in ulcerative colitis was associated with improved survival and delayed colectomy. However, improvement was not related to the anticipated benefits of improved cancer-related survival.

Adolescent↗

Effect of folate supplementation on the incidence of dysplasia and cancer in chronic ulcerative colitis. A case-control study.

Folate deficiency has been associated with dysplasia in human cancer models. Patients with ulcerative colitis commonly have decreased folate levels, which are partially due to sulfasalazine, a competitive inhibitor of folate absorption. To study the effect of folate supplementation on the risk of dysplasia or cancer (neoplasia) in ulcerative colitis, records from 99 patients with pancolitis for greater than 7 yr and enrolled in a surveillance program were reviewed. Thirty-five patients with neoplasia were compared with 64 patients in whom dysplasia was never found to determine the effect of folate supplementation on the rate of development of neoplasia using case-control methodology. At the time of the index colonoscopy, patients with neoplasia were older (43 +/- 11 vs. 39 +/- 12 yr) and had disease of longer duration (20 +/- 8 vs. 15 +/- 7 yr, p less than 0.05). Folate supplementation was associated with a 62% lower incidence of neoplasia compared with individuals not receiving supplementation (odds ratio, 0.38; 95% confidence interval, 0.12-1.20). There was no appreciable change in this effect when models were fit to adjust for sulfasalazine dose, duration of disease, age at symptom onset, prednisone dose, sulfa allergy, sex, race, or family history of colon cancer. The statistical power of the association between folate supplementation and neoplasia was 72%. Correction of risk factors before the development of neoplasia may prevent this serious complication. Pending a larger case-control study, folate supplementation during sulfasalazine administration is recommended to possibly prevent the complication of dysplasia or cancer in ulcerative colitis.

Adult↗