Improvement In Overall Symptoms Research Articles

A new method of construction of obturators for nasal septal perforations and evidence of outcomes

Septal obturators and buttons for nasal septal perforations are often poorly tolerated. We describe a new method of obturator construction using three-dimensional imaging which more closely replicates the true anatomy of the defect. Patients were assessed using a questionnaire relating to how symptoms had changed between having no obturator, a conventional obturator and the new CT obturator. Eight of nine patients had an improvement in total symptom scores comparing old obturators to new CT obturators and this was significant with a P-value of 0.018 using Student's paired t-test. The majority of patients were satisfied with the new obturators and reported an overall improvement of symptoms.

Intra-anal collagen injection for the treatment of faecal incontinence

Intra-anal injectable agents have been used to treat faecal incontinence. The aim of this study was to report the experience of a cohort of patients who underwent intra-anal injection of collagen and to determine which patients benefited from the technique. Data, including age, sex, incontinence score, classification of incontinence, baseline resting pressure and vector volume, were collected prospectively for 73 consecutive patients (59 women) undergoing intra-anal collagen injection. Patients were reviewed after treatment and incontinence scores documented. A proportion of patients also underwent repeat anorectal physiological testing 8 weeks after the procedure. At a median follow-up of 12 months after the intra-anal injection, 63 per cent of patients had an improved incontinence score and 73 per cent reported an overall improvement in symptoms. Logistic regression showed that older age and idiopathic faecal incontinence were predictors of a successful outcome (P = 0.042 and P = 0.048 respectively). Intra-anal collagen injection appears to have a role in the treatment of faecal incontinence. The majority of patients can expect both objective and subjective improvement. The best results are achieved in older patients and in those with idiopathic incontinence.

Influence of Treatment of Erosive Lichen Planus of the Vulva on Its Prognosis

To record the clinical features, symptomatic response to treatment, and resolution of clinical signs in a large cohort of women with erosive lichen planus of the vulva. Descriptive, prospective cohort study with a mean follow-up of 72 months. The vulval clinics of a teaching and district general hospital in Oxfordshire, England. One hundred fourteen adult women with a definite clinical diagnosis of erosive lichen planus of the vulva.Interventions Patients received topical corticosteroids with or without other topical preparations and systemic treatments as part of their normal care. Symptomatic response to individual treatments (good, partial, or poor), overall symptomatic response to treatment and with time (good, partial, no change, or worse), response of the vulval signs (total, partial, moderate, minor, same, or worse), and the presence or absence of moderate or severe scarring. The mean age at onset of vulval symptoms was 56.9 years. First-line therapy was an ultrapotent topical corticosteroid in 89 women (78%), of whom 63 (71%) were symptom free while receiving treatment. Overall and with time, 86 women (75%) improved with treatment, including 62 (54%) who were symptom free (good response) and 24 (21%) who had a partial response. Eighteen (16%) had no change and 10 (9%) were worse. Overall response of the vulval signs was recorded in 113 patients. Only 10 (9%) of these had complete resolution of clinical signs excepting scarring, with 57 (50%) showing resolution of erosions. Squamous cell carcinoma developed in 3 women (3%). Topical ultrapotent corticosteroid is an effective treatment for erosive lichen planus of the vulva, giving relief of symptoms in 71%. With time and treatment, three quarters of patients can expect overall improvement of symptoms and one half, healing of erosions.

Treatment of severe postvagotomy/postgastrectomy symptoms with the somatostatin analogue octreotide

Fourteen patients with severe and persistent postvagotomy/postgastrectomy symptoms were entered into a trial of treatment with the somatostatin analogue octreotide, 50 micrograms twice daily 30 min before meals being self-administered by subcutaneous injection. Six of the seven patients completing the 3-month trial showed sustained overall improvement of symptoms. The remaining patients were unhelped by treatment or developed unwanted effects. Six of eight patients with dumping syndrome showed sustained improvement of dumping symptoms during treatment. Bile vomiting was relieved in three of four patients with this complaint. Diarrhoea accompanying dumping showed a variable response to treatment, with improvement in three patients and no change or worsening of this symptom in five. Two patients with severe postvagotomy diarrhoea alone showed no improvement. Four patients with unwanted effects and three patients who found no benefit stopped the trial medication early. Four further patients reported mild or transient side-effects. For patients with severe postvagotomy/postgastrectomy symptoms, a trial of octreotide seems justified when significant dumping symptoms are present and other treatment options have been exhausted.

A comparative study between crepe bandage, tensopress, and panelast following varicose vein operations

This study was conducted in a district general hospital to compare the effect of three types of bandages applied following standard varicose vein operations. The three bandages studied were Crêpe® bandage, Tensopress®, and Panelast®. The study included 60 patients and took place over a period of a year. All patients coming for a varicose veins operation were included in the study, including those with recurrent varicose veins. Patients were assessed before and after the operation and changes were recorded. The study showed that 91% of patients benefited from the operation, and their symptoms improved significantly. However, there was no significant difference among the different bandage groups with respect to the overall improvement in symptoms (p= 0.004) and cosmetic appearance (p = 0.005). Tensopress showed significant control of bleeding than did the other two bandages (p > 0.05), and Crepe bandage showed improvement in leg swelling (p > 0.05) and was more comfortable than the other two bandages (p = 0.1). There were no mortalities, and 91% of patients were treated satisfactorily as day surgery.

Histamine-2 receptor antagonists at night improve gastroesophageal reflux disease symptoms for patients on proton pump inhibitor therapy

While night-time symptoms of gastroesophageal reflux disease (GERD) are common, considerable controversy exists regarding the use of histamine-2 receptor antagonists (H2Ras) for night-time reflux control. Some studies have suggested possible tolerance to H2RA while others have suggested that long-term efficacy of gastric acid control can be maintained with night-time H2RA use. The aim of this study was to identify if GERD patients have sustained symptom improvement with long-term use of night-time H2RA. Records of 56 consecutive GERD patients on twice daily proton pump inhibitor (PPI) and night-time H2RA therapy were reviewed. During a phone interview patients were asked a 5-item questionnaire, which included overall assessment of symptoms, night-time symptoms, sleep disturbance, duration and frequency of therapy. Of the 56 patients, 39 (31 women, mean age 56) completed the questionnaire (15 were not reached and 2 did not recall enough information). All respondents had taken night-time H2RA for at least 1 month (28/39 patients with > 6 months duration) with 33/39 patients taking H2RAs every night. The addition of H2RA led to an improvement in overall symptoms in 28/39 (72%) patients, improvement in night-time reflux symptoms in 25/34 (74%) patients and improvement of GERD-associated sleep disturbance in 18/27 (67%) patients. Five (13%) patients had stopped the H2RA on their own, stating that its efficacy waned after 1 month. Our results suggest that the majority of patients report persistent improvement in GERD symptoms from night-time H2RA use and that possible clinically important tolerance to H2RAs occurs in a small number of patients. Further prospective, placebo-controlled studies may help confirm that there is a role for night-time H2RAs in GERD symptom control.

Nizatidine for the treatment of pediatric gastroesophageal reflux symptoms: An open-label, multiple-dose, randomized, multicenter clinical trial in 210 children

Background: Gastroesophageal reflux disease (GERD), which is reflux that produces damage or troubling symptoms, afflicts ∼7% of infants and children to the extent that administration of physician-directed pharmacotherapy is warranted. Objective: This study was designed in conjunction with the US Food and Drug Administration (FDA) to assess the tolerability and effectiveness of nizatidine, in different doses and formulations, including a newly formulated premade oral solution, for pediatric GERD. Methods: Children aged 5 days through 18 years were recruited to this 8-week, open-label, multiple-dose, randomized, parallel-group, multicenter study. The original study design specified that patients aged 5 days through 12 years at study start be given a nizatidine capsule dissolved in infant formula or apple juice depending on patient age (“extemporaneous solution”). Children 13 through 18 years old were to be given the “adult dose” of nizatidine capsules 150 mg BID regardless of body weight. All patients aged <13 years were randomized in blocks of 4 between 2 dose levels (2.5 and 5 mg/kg per dose BID). A protocol amendment during the study added a newly formulated, more pediatric-appropriate, premade oral solution that was developed at the request of the FDA. This premade formulation (“oral solution”) was to replace the extemporaneous solution mixed in infant formula or apple juice. Subsequently, an additional 44 children aged <13 years old were enrolled in the study and randomized to receive the new nizatidine oral solution for 8 weeks at the same 2 dose levels as used for the extemporaneous solution. Outcome data at 4 and 8 weeks included adverse events (AEs) (severity, relation to study drug, and any relationship to study withdrawal) and effectiveness (investigators' assessment of changes in reflux symptoms and overall physical well-being, and parent/child assessment of change in antacid use). Formal statistical analyses were not planned, but post hoc chi-square analyses were performed. Results: Of 214 children enrolled, 210 (98%) intentto-treat (ITT) patients received ≥1 dose; of these, 173 (82%) completed 8 weeks of study. At least 77% were compliant (ie, medicated on ≥75% of days). Of the ITT patients, 37 did not complete 8 weeks due to insufficient response, AEs (regardless of relationship to study drug), or other reasons. Although 292 AEs occurred in 115 patients, 277 (95%) were mild to moderate and 15 (5%) were severe. Most of the AEs in these children studied during the winter were related to infectious illnesses. Only 4 serious AEs occurred; 3 were unrelated to study drug. The fourth AE—considered possibly related—was worsening sickle cell anemia 18 days after medication discontinuation. Approximately 30% of patients became asymptomatic after 8 weeks of treatment, regardless of dosing or formulation, and despite reduction of antacid use in half of the patients. No clear superiority of any dose or formulation was demonstrated. Conclusions: This large study, although limited by its open-label design and post hoc analyses, supports the tolerability and effectiveness of 8 weeks of treatment with nizatidine in children aged 5 days through 18 years. AE incidence and severity were as expected for children during the winter season. There was an overall improvement in symptoms and a decrease in antacid use. Formulation did not appear to alter tolerability or effectiveness assessments: the premade solution, extemporaneous solution, and capsule provided comparable symptomatic relief with no disproportionate adverse reactions.

The placebo effect in irritable bowel syndrome trials: a meta‐analysis1

Despite the apparent high placebo response rate in randomized placebo-controlled trials (RCT) of patients with irritable bowel syndrome (IBS), little is known about the variability and predictors of this response. To describe the magnitude of response in placebo arms of IBS clinical trials and to identify which factors predict the variability of the placebo response. We performed a meta-analysis of published, English language, RCT with 20 or more IBS patients who were treated for at least 2 weeks. This analysis is limited to studies that assessed global response (improvement in overall symptoms). The variables considered as potential placebo modifiers were study design, study duration, use of a run-in phase, Jadad score, entry criteria, number of office visits, number of office visits/study duration, use of diagnostic testing, gender, age and type of medication studied. Forty-five placebo-controlled RCTs met the inclusion criteria. The placebo response ranged from 16.0 to 71.4% with a population-weighted average of 40.2%, 95% CI (35.9-44.4). Significant associations with lower placebo response rates were fulfillment of the Rome criteria for study entry (P=0.049) and an increased number of office visits (P=0.026). Placebo effects in IBS clinical trials measuring a global outcome are highly variable. Entry criteria and number of office visits are significant predictors of the placebo response. More stringent entry criteria and an increased number of office visits appear to independently decrease the placebo response.

Emerging Trends in the Management of Heart Failure: Beta Blocker Therapy

There is overwhelming evidence that beta blocker therapy in the form of metoprolol, bisoprolol, and carvedilol can have positive outcomes on morbidity, mortality, and quality of life in patients who have been diagnosed with mild to severe heart failure. Barring contraindications, beta blockers should be considered a cornerstone of therapy for these patients along with ACE inhibitors and diuretics. Beta blocking drugs are effective in modifying the cascade of events that occur as a result of the neurohormonal response that leads to the devastating effects evident during heart failure. Long-term effects of beta blockade include an increase in cardiac output, an increase in exercise tolerance, a decrease in the number of hospitalizations, and an overall improvement in symptoms.

Role of anal dilatation in treatment of idiopathic constipation in children: long-term follow-up of a double-blind randomized controlled study

Constipation in childhood is a common symptom, with an estimated incidence between 0.3% and 8%. Most of the evidence for the current management of constipation and fecal soiling in children is based on reports of nonrandomized retrospective trials. Anal dilatation has had an established role in the management of idiopathic constipation but has never been evaluated by a randomized study. A double-blind randomized controlled trial was done of children who failed to respond to medical treatment and were admitted for investigation and treatment of idiopathic constipation to Guy's Hospital, London, between April 2001 and April 2003. All children had intestinal transit study on admission. They were randomized, using a computer-generated allocation in sealed envelopes, to receive no anal dilatation (control group) or anal dilatation (anal dilatation group). Anorectal manometry and endosonography were done under ketamine anesthesia followed by anal dilatation if necessary under the same anesthesia. Disimpaction of feces from the rectum was done at the end of the procedure under general anesthesia using propofol muscle relaxant to minimize stretching of anal sphincter muscles in the control group. All children had intensification of medical treatment, toilet training, and monitoring of their response to treatment during their hospital stay, which ranged from 3 to 5 days. Outcome was measured using a parent's questionnaire of symptom severity at 3 and 12 months of follow-up by one of the authors, who was blinded to randomization. The symptom severity score ranged between 0 and 65 and consisted of scores for the following: delay in defecation (score range 0-10), difficulty and pain with passing stool (0-5), soiling problem (0-10), intensity of laxative treatment (0-10), child's general health (0-5), behavior related to the bowel problem (0-5), overall improvement of symptoms (0-12,) and assessment of megarectum on abdominal examination (0-8). Of 60 neurologically normal children, 31 (19 males) were randomized in the control group and 29 (18 males) in the anal dilatation group. All children had findings consistent with idiopathic constipation and positive anorectal reflex on manometry, no anal sphincter damage on endosonography, and no anal fissure on examination under anesthesia. The median age for control and anal dilatation groups was 7.97 (range 4.1-14.25) years and 7.78 (4-13.25) years, respectively. Both groups were also comparable with regard to median of duration of laxative treatment (32 months vs. 31.5 months), internal anal sphincter thickness on endosonography (0.90 mm vs. 0.80 mm), resting anal sphincter pressure on manometry (51 mmHg vs. 51 mmHg), total rectal capacity on manometry (260 mmHg vs. 260 mmHg), and total symptom severity score before admission (33 vs. 29), respectively. At 12-month follow-up, the median pre-admission symptom severity score had improved significantly, from 33 (range 12-49) in the control group and 29 (16-51) in the dilatation group to 15 (0-51, p < 0.0001) and 19 (1-46, p < 0.0001), respectively. There was no significant difference between the two groups with regard to symptom severity score improvement at 12-month follow-up (p < 0.92). We found a significant correlation between total rectal capacity measured on manometry and symptom severity score before admission and at 12-month follow-up (r = 0.30, p < 0.01 and r = 0.25, p < 0.05, respectively). Our results indicate that anal dilatation does not contribute to the management of school-aged children with idiopathic constipation. Admission to hospital for clarification of diagnosis and intensification of medical treatment with disimpaction of stool from the rectum is beneficial.

Maintenance therapy with ribavirin in patients with chronic hepatitis C who fail to respond to combination therapy with interferon alfa and ribavirin

To assess the efficacy and safety of maintenance therapy with ribavirin alone in chronic hepatitis C, 108 patients were treated with the combination of interferon alfa and ribavirin for 24 weeks; those who failed to have a virologic response were offered enrollment in a randomized, double-blind, controlled trial of ribavirin (1,000-1,200 mg daily) versus placebo for the subsequent 48 weeks. Patients were monitored at regular intervals with symptom questionnaires, serum aminotransferase levels, hepatitis C virus (HCV) RNA levels, and complete blood counts and underwent liver biopsy at the completion of therapy. Among 108 patients, 50 were still HCV RNA positive after 24 weeks of treatment, of whom 34 agreed to be randomized to continue either ribavirin monotherapy or placebo. Among 17 patients who received placebo, there was no overall improvement in symptoms, serum alanine aminotransferase (ALT) levels, HCV RNA levels, or hepatic histology. Among the 17 patients who received ribavirin, serum ALT levels and necroinflammatory features of liver histology were improved, whereas symptoms, HCV RNA levels, and hepatic fibrosis scores were not changed significantly from baseline. Responses to ribavirin seemed to be categorical, such that 8 patients (47%) had definite improvement in liver histology. Patients with improved histology had improvements in serum ALT levels both on combination therapy and after switching to ribavirin monotherapy. In conclusion, continuation of ribavirin monotherapy may maintain serum biochemical improvements that occur during interferon-ribavirin combination therapy in some patients and that these improvements are often associated with decreases in necroinflammatory changes in the liver. Whether these improvements will ultimately result in prevention of progression of hepatitis C requires further study. (H epatology 2003;38:66-74.)

Spondylolysis of l2 in identical twins

Objective To discuss the presence of spondylolysis at L2 in identical twins. Clinical features Twin 61-year-old brothers reported insidious low back pain (LBP) of relatively recent onset. Both engaged in running as their main form of exercise. One had spondylolisthesis and history of significant traumatic incident; the other had no spondylolisthesis but a much more strenuous running regimen. Intervention and outcome Both patients underwent a course of chiropractic treatment for mechanical LBP and reported a 50% overall improvement in symptoms. Conclusions Spondylolysis at L2 is uncommon, and although a familial component regarding weakness of the pars interarticularis has been demonstrated in the literature, spondylolysis at L2 in twins is extremely rare. Questions remain regarding the cause of spondylolisthesis in patients.

Release of Tension-Free Vaginal Tape for the Treatment of Refractory Postoperative Voiding Dysfunction

In Brief OBJECTIVE To report our experience with surgical release of tension-free vaginal tape (TVT) for the treatment of persistent post-TVT voiding dysfunction. METHODS A total of 1175 women underwent TVT placement for treatment of genuine stress urinary incontinence and/or intrinsic sphincter deficiency over a 2-year period. Additional procedures and vaginal repairs were performed as indicated. Among these patients, 23 women (1.9%) had persistent voiding dysfunction (urinary retention, incomplete bladder emptying, or severe urgency or urge incontinence) refractory to conservative management. This cohort underwent a simple vaginal TVT release procedure, performed on an outpatient basis. Preoperative characteristics, intraoperative, and postoperative details were assessed by review of operative notes, medical records, and office notes. Continence status was assessed using subjective and objective information. RESULTS Mean age was 67 years (range 46–86 years), and the mean interval between TVT placement and release was 17.3 weeks (range 2–69 weeks; median 8.6 weeks). For the release procedure, there were no intraoperative complications, and all patients were discharged on the day of surgery. All cases of impaired emptying were completely resolved, and all cases of irritative symptoms were resolved (30%) or improved (70%) by 6 weeks. Fourteen (61%) patients remained continent 6 weeks after the release procedure, six (26%) were improved over baseline, and three patients (13%) had recurrence of stress incontinence. CONCLUSION Refractory voiding dysfunction after TVT is a relatively uncommon situation and can be successfully managed with a simple midline release procedure. In most cases, the release procedure does not compromise overall improvement in symptoms of stress incontinence. Persistent post–tension-free vaginal tape voiding dysfunction is effectively treated with a simple vaginal release procedure, without unduly compromising continence benefits.

Release of tension-free vaginal tape for the treatment of refractory postoperative voiding dysfunction

OBJECTIVE: To report our experience with surgical release of tension-free vaginal tape (TVT) for the treatment of persistent post-TVT voiding dysfunction. METHODS: A total of 1175 women underwent TVT placement for treatment of genuine stress urinary incontinence and/or intrinsic sphincter deficiency over a 2-year period. Additional procedures and vaginal repairs were performed as indicated. Among these patients, 23 women (1.9%) had persistent voiding dysfunction (urinary retention, incomplete bladder emptying, or severe urgency or urge incontinence) refractory to conservative management. This cohort underwent a simple vaginal TVT release procedure, performed on an outpatient basis. Preoperative characteristics, intraoperative, and postoperative details were assessed by review of operative notes, medical records, and office notes. Continence status was assessed using subjective and objective information. RESULTS: Mean age was 67 years (range 46–86 years), and the mean interval between TVT placement and release was 17.3 weeks (range 2–69 weeks; median 8.6 weeks). For the release procedure, there were no intraoperative complications, and all patients were discharged on the day of surgery. All cases of impaired emptying were completely resolved, and all cases of irritative symptoms were resolved (30%) or improved (70%) by 6 weeks. Fourteen (61%) patients remained continent 6 weeks after the release procedure, six (26%) were improved over baseline, and three patients (13%) had recurrence of stress incontinence. CONCLUSION: Refractory voiding dysfunction after TVT is a relatively uncommon situation and can be successfully managed with a simple midline release procedure. In most cases, the release procedure does not compromise overall improvement in symptoms of stress incontinence.

Biofeedback for anismus: has placebo effect been overlooked?

Multiple uncontrolled studies have concluded that biofeedback is successful in treating anismus. This study's objective was to assess the physiological effects of placebo and biofeedback treatment on patients with anismus and to correlate changes with clinical improvement. Twelve patients with symptoms and electrophysiological findings of anismus were studied. Initial assessment included a detailed history, symptom assessment by linear analogue scales, anorectal manometric and electrophysiological studies, colon transit scintigraphy, and scintigraphic proctography. Patients underwent 5 days of placebo treatment, followed 1 week later by re-assessment of symptoms and physiological studies. Five days of biofeedback was then given followed by another complete re-assessment 1 week later. A final interview was performed 2 months later. All assessments were by an independent observer who was not responsible for the treatments. Seven patients reported an overall improvement in symptoms following placebo treatment. A total of seven patients reported improvement following biofeedback, three of whom had already reported an improvement with placebo. One patient who reported improvement following placebo had worsening of symptoms following biofeedback. The only symptoms or tests which changed more with biofeedback than placebo were anal pressure and electromyographic activity on attempted defaecation in the left lateral position. There was no demonstrable correlation between change in symptoms and change in physiological tests. The scintigraphic 'ejection fraction' of the rectum was unchanged by treatment. Clinical improvement in previous studies may in part be due to placebo effect and observer bias. Improvement with biofeedback may be due to physiological changes which are not detected with conventional anorectal physiological tests.

Evaluation of omeprazole as a cost-effective diagnostic test for gastro-oesophageal reflux disease.

There is a need for a simple, therapeutic test that is of diagnostic value and can also provide rapid symptom relief in patients who present with classic, mild symptoms suggestive of gastro-oesophageal reflux disease (GERD), when the diagnosis is based on symptom assessment alone. To assess the diagnostic value of a therapeutic trial of omeprazole 40 mg in a dyspeptic population. A total of 90 patients with symptoms suggestive of GERD entered the study. Patients underwent endoscopy and ambulatory oesophageal pH monitoring for 18-24 h. Patients then received omeprazole 40 mg o.m. for 2 weeks. There was a significant correlation between the diagnoses obtained from a trial of omeprazole and the diagnoses obtained from pH monitoring (P < 0. 05). There was no significant correlation between the diagnoses obtained from endoscopy and those obtained from pH monitoring. Both omeprazole and endoscopy were compared to pH monitoring as the 'gold standard' for the diagnosis of GERD and the cost per correct diagnosis with omeprazole was pound47 (95% CI: pound40- pound59) compared to pound480 (95% CI: pound396- pound608) with endoscopy. There was a complete absence of acid-related symptoms in the majority (59%) of patients after 3 days of omeprazole 40 mg therapy and, after 2 weeks, 82% of patients had experienced an improvement in overall symptoms ( 1 grade). We conclude that omeprazole can be used as a clinically effective tool in the initial management of GERD and that it is of diagnostic value in patients who present with typical symptoms, such as heartburn, when the diagnosis is based on symptom assessment alone.

Practical recommendations for the management of adenocarcinoma of the pancreas.

Pancreatic cancer is widely regarded by medical personnel and the lay public as one of the most dreaded of all diagnoses. Although in selected series of operable patients the chance of long term survival may reach 20%, most patients have unfavourable disease at the time of diagnosis, and for the entire group of newly diagnosed patients, 5-year survival is rare. This grim outlook results from a combination of factors, including an anatomical location which makes early detection by screening tests or by symptoms difficult, a high tendency for spread to regional lymphatics and the liver, a poor profile of sensitivity to chemotherapeutic agents and the poor medical condition of many patients at the time of diagnosis. These factors mean that it is particularly important that at the time of diagnosis these patients are carefully evaluated, and that they and their families are fully aware of the treatment options available to them and the associated potential risks and benefits. For localised cancers, surgical resection alone offers the potential for long term survival. The addition of postoperative radiation therapy (RT) predictably improves local control but has minimal impact on survival, which is primarily determined by the development of liver metastases. Randomised trial data support the use of combined fluorouracil (5-FU) chemotherapy and RT in patients who have undergone pancreatectomy and have negative margins, although the benefits are modest and the relevant randomised trials enrolled relatively small patient numbers. For patients with marginally resectable tumours, the feasibility has been demonstrated of using chemotherapy plus RT to reduce tumour size before resection, but it is unclear whether this approach will benefit a significant number of patients. Tumours which are unresectable because of local advancement (involvement of major vessels or regional nodes) can be treated with RT alone or in combination with chemotherapy, but survival past 2 years is uncommon. Patients with liver metastases have a poor prognosis. As part of a programme of supportive care, some of these patients may receive cytotoxic therapy, the goal of which is to relieve cancer-related symptoms such as pain from the primary tumour or metastatic sites, or weakness, nausea and anorexia which may be associated with liver metastases. Although the objective response rate of chemotherapy agents is low, in an individual patient they may produce an adequate response and acceptable toxicity so that the patient experiences overall improvement in symptoms. The mainstay of chemotherapy for pancreatic cancer, as with other gastrointestinal cancers, has been fluorouracil. However, recent clinical data have shown that gemcitabine produces similar results in terms of response rate and survival, with more acceptable toxicity, so that the quality of life was judged to be better than with fluorouracil. Pancreatic cancer provides a fertile ground for testing new, biologically based approaches to cancer therapy because of the limited success of currently available treatments.

Pygeum africanum for benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH), nonmalignant enlargement of the prostate, can lead to obstructive and irritative lower urinary tract symptoms (LUTS). The pharmacologic use of plants and herbs (phytotherapy) for the treatment of LUTS associated with BPH has been growing steadily. The extract of the African prune tree, Pygeum africanum, is one of the several phytotherapeutic agents available for the treatment of BPH. To investigate the evidence whether extracts of Pygeum africanum (1) are more effective than placebo in the treatment of Benign Prostatic Hyperplasia (BPH), (2) are as effective as standard pharmacologic BPH treatments, and (3) have less side effects compared to standard BPH drugs. Trials were searched in computerized general and specialized databases (MEDLINE (1966-2000), EMBASE, Cochrane Library, Phytodok), by checking bibliographies, and by contacting relevant manufacturers and researchers. Trials were eligible if they (1) were randomized (2) included men with BPH (3) compared preparations of Pygeum africanum (alone or in combination) with placebo or other BPH medications (4) included clinical outcomes such as urologic symptom scales, symptoms, or urodynamic measurements. Eligibility was assessed by at least two independent observers. Information on patients, interventions, and outcomes were extracted by at least two independent reviewers using a standard form. The main outcome measure for comparing the effectiveness of Pygeum africanum with placebo and standard BPH medications was the change in urologic symptoms scale scores. Secondary outcomes included change in urologic symptoms including nocturia and urodynamic measures (peak and mean urine flow, prostate size). The main outcome measure for adverse effects was the number of men reporting adverse effects. A total of 18 randomized controlled trials involving 1562 men met inclusion criteria and were analyzed. Only one of the studies reported a method of treatment allocation concealment, though 17 were double-blinded. There were no studies comparing Pygeum africanum to standard pharmacologic interventions such as alpha-adrenergic blockers or 5-alpha reductase inhibitors. The mean study duration was 64 days (range, 30-122 days). Many studies did not report results in a method that permitted meta-analysis. Compared to men receiving placebo, Pygeum africanum provided a moderately large improvement in the combined outcome of urologic symptoms and flow measures as assessed by an effect size defined by the difference of the mean change for each outcome divided by the pooled standard deviation for each outcome (-0.8 SD [95% confidence interval (CI), -1.4, -0.3 (n=6 studies)]). Men using Pygeum africanum were more than twice as likely to report an improvement in overall symptoms (RR=2.1, 95% CI = 1.4, 3.1). Nocturia was reduced by 19%, residual urine volume by 24% and peak urine flow was increased by 23%. Adverse effects due to Pygeum Africanum were mild and comparable to placebo. The overall dropout rate was 12% and was similar between Pygeum Africanum (13%), placebo (11%) and other controls (8%). A standardized preparation of Pygeum africanum may be a useful treatment option for men with lower urinary symptoms consistent with benign prostatic hyperplasia. However, the reviewed studies were small in size, were of short duration, used varied doses and preparations and rarely reported outcomes using standardized validated measures of efficacy. Additional placebo-controlled trials are needed as well as studies that compare Pygeum africanum to active controls that have been convincingly demonstrated to have beneficial effects on lower urinary tract symptoms related to BPH. These trials should be of sufficient size and duration to detect important differences in clinically relevant endpoints and use standardized urologic symptom scale scores.

Primary Bladder Neck Obstruction: Urodynamic Findings and Treatment Results in 36 Men

Purpose We reviewed the urodynamic findings and treatment outcomes of a large series of men with primary bladder neck obstruction. Materials and Methods A retrospective review was done of the presenting symptoms and urodynamic findings of 36 men with primary bladder neck obstruction. Outcomes after treatment with alpha-blockers, transurethral incision of the bladder neck and prostate, or no long-term therapy were determined by chart review and patient survey in the majority of cases. Results Mean age of the men was 41 years. Patients had significant lower urinary tract symptoms, decreased peak urinary flow rates, elevated post-void residual, markedly elevated peak voiding pressures and poor funneling of the bladder neck during voiding. Although most patients initially chose alpha-blocker therapy, only 30 percent of those beginning alpha-blockers continued them long term, usually due to inadequate symptomatic improvement. A total of 18 men underwent transurethral incision, which resulted in significant improvements in symptom scores, peak urinary flow rates, post-void residual and peak voiding pressures. Patients reported a mean 87 percent overall improvement in symptoms after transurethral incision. Conclusions Video urodynamics facilitate diagnosis of primary bladder neck obstruction. Transurethral incision is the most effective therapy for primary bladder neck obstruction.

Atlanto-axial subluxation in down's syndrome

Atlanto-axial subluxation, which was causing symptoms in eight patients with Down's syndrome, was treated by operation. In every case various congenital bony anomalies were found. Marked myelopathy was present in four cases of ossiculum terminale, and mild myelopathy in one with anteroposterior spondyloschisis. Successful posterior arthrodesis was performed from C1 to C2 in six cases, and from the occiput to C2 in the other two patients with anteroposterior spondyloschisis. Excellent bony union and an overall improvement in symptoms was achieved. The follow-up period was from one year to five years and six months. Early surgical stabilization is the treatment of choice in those cases of symptomatic atlanto-axial subluxation in Down's syndrome where there are congenital osseous anomalies and generalised ligamentous laxity, and where the spinal cord is at risk.