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[A comparative study of the effects of drug therapy and bladder training therapy].

Treatment of enuresis was studied in 168 patients. The patients were divided into two groups, the drug therapy group which consisted of 88 patients who were treated with drugs only, and the bladder training therapy group which consisted of 80 patients who were treated mainly with bladder training supplemented with drug therapy. In the drug therapy group imipramine was the first choice and was used at bed time. The dose of imipramine was initially 1 mg/kg and was gradually decreased if it worked well, and changed to other drugs if it did not work well. In the bladder training therapy group, bladder training was performed in all patients for 3 months, and 22 patients who cured further bladder training was continued, whereas the rest of the patients (58 patients) drug therapy was started in addition to bladder training. After 3 months, drug therapy was effective for 54 patients (61%) including 10 patients (11%) who were cured, and bladder training therapy plus drug therapy was effective for 55 patients (69%) including 22 patients (28%) who were cured. The number of cured patients in the bladder training therapy group was significantly larger than that of the drug therapy group (p less than 0.01). After 6 months, drug therapy was effective for 56 patients (64%) including 16 patients (18%) who were cured, and bladder training therapy plus drug therapy was effective for 66 patients (83%) including 30 patients (38%) who were cured. The number of effective and cured patients in the bladder training therapy group was significantly larger than that in the drug therapy group (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Manual therapy, physical therapy, or continued care by a general practitioner for patients with neck pain. A randomized, controlled trial.

BACKGROUND: Neck pain is a common problem, but the effectiveness of frequently applied conservative therapies has never been directly compared. OBJECTIVE: To determine the effectiveness of manual therapy, physical therapy, and continued care by a general practitioner. DESIGN: Randomized, controlled trial. SETTING: Outpatient care setting in the Netherlands. PATIENTS: 183 patients, 18 to 70 years of age, who had had nonspecific neck pain for at least 2 weeks. INTERVENTION: 6 weeks of manual therapy (specific mobilization techniques) once per week, physical therapy (exercise therapy) twice per week, or continued care by a general practitioner (analgesics, counseling, and education). MEASUREMENTS: Treatment was considered successful if the patient reported being "completely recovered" or "much improved" on an ordinal six-point scale. Physical dysfunction, pain intensity, and disability were also measured. RESULTS: At 7 weeks, the success rates were 68.3% for manual therapy, 50.8% for physical therapy, and 35.9% for continued care. Statistically significant differences in pain intensity with manual therapy compared with continued care or physical therapy ranged from 0.9 to 1.5 on a scale of 0 to 10. Disability scores also favored manual therapy, but the differences among groups were small. Manual therapy scored consistently better than the other two interventions on most outcome measures. Physical therapy scored better than continued care on some outcome measures, but the differences were not statistically significant. CONCLUSION: In daily practice, manual therapy is a favorable treatment option for patients with neck pain compared with physical therapy or continued care by a general practitioner.

Adolescent↗

Spinal manipulative therapy for low back pain. A meta-analysis of effectiveness relative to other therapies.

BACKGROUND: Low back pain is a costly illness for which spinal manipulative therapy is commonly recommended. Previous systematic reviews and practice guidelines have reached discordant results on the effectiveness of this therapy for low back pain. PURPOSE: To resolve the discrepancies related to use of spinal manipulative therapy and to update previous estimates of effectiveness by comparing spinal manipulative therapy with other therapies and then incorporating data from recent high-quality randomized, controlled trials (RCTs) into the analysis. DATA SOURCES: MEDLINE, EMBASE, CINAHL, the Cochrane Controlled Trials Register, and previous systematic reviews. STUDY SELECTION: Randomized, controlled trials of patients with low back pain that evaluated spinal manipulative therapy with at least 1 day of follow-up and at least one clinically relevant outcome measure. DATA EXTRACTION: Two authors, who served as the reviewers for all stages of the meta-analysis, independently extracted data from unmasked articles. Comparison treatments were classified into the following seven categories: sham, conventional general practitioner care, analgesics, physical therapy, exercises, back school, or a collection of therapies judged to be ineffective or even harmful (traction, corset, bed rest, home care, topical gel, no treatment, diathermy, and minimal massage). DATA SYNTHESIS: Thirty-nine RCTs were identified. Meta-regression models were developed for acute or chronic pain and short-term and long-term pain and function. For patients with acute low back pain, spinal manipulative therapy was superior only to sham therapy (10-mm difference [95% CI, 2 to 17 mm] on a 100-mm visual analogue scale) or therapies judged to be ineffective or even harmful. Spinal manipulative therapy had no statistically or clinically significant advantage over general practitioner care, analgesics, physical therapy, exercises, or back school. Results for patients with chronic low back pain were similar. Radiation of pain, study quality, profession of manipulator, and use of manipulation alone or in combination with other therapies did not affect these results. CONCLUSIONS: There is no evidence that spinal manipulative therapy is superior to other standard treatments for patients with acute or chronic low back pain.

Acute Disease↗

Health-related quality-of-life after external beam radiation therapy for localized prostate cancer: intensity-modulated radiation therapy versus conformal radiation therapy.

We compared health-related quality-of-life (HRQL) after intensity-modulated radiotherapy (IMRT) with statuses obtained after old and new protocols of three-dimensional conformal radiation therapy (3DCRT) for localized prostate cancer. We measured the general and disease specific HRQL using the MOS 36-Item Health Survey (SF-36), and the University of California, Los Angeles Prostate Cancer Index (UCLA PCI), respectively. IMRT resulted in similar profiles of general and disease-specific HRQL to two other methods within the first year after treatment. Moreover, IMRT gave rise to comparable urinary, intestinal and sexual side effects despite the high dose of radiation applied.

Aged↗

Comparison of immunologic restoration and virologic response in plasma, tonsillar tissue, and cerebrospinal fluid in HIV-1-infected patients treated with double versus triple antiretroviral therapy in very early stages: The Spanish EARTH-2 Study. Early Anti-Retroviral Therapy Study.

The objective of antiretroviral therapy is to obtain an almost complete and durable suppression of viral replication in all compartments to facilitate recovery of the immune system. We assessed the virologic effect in plasma, tonsillar tissue, and cerebrospinal fluid (CSF) in 94 HIV-1-infected patients with CD4 counts >500 x 106 cells per liter and viral load >5000 copies/ml randomly assigned to triple antiretroviral therapy (two nucleoside reverse transcriptase inhibitors (NRTIs) plus one protease inhibitor) versus double therapy (two NRTIs). We also analyzed the immunologic recovery in this cohort of patients. Lymphoid tissue and cerebrospinal fluid viral load, development of genotypic resistance, proliferative responses to HIV-1 specific antigens, and other immunophenotypic markers were analyzed. The proportion of patients who achieved a decrease in HIV RNA levels to <200 copies/ml was significantly greater in the triple therapy group than in the two drug groups (p =.0002 for each pair-wise difference). At week 52, tonsillar tissue HIV RNA from 5 patients treated with triple therapy was lower than the limit of detection, whereas the mean +/- standard error in patients with double therapy (n = 5) was 5.03 +/- 0.34 copies/mg/tissue. In all 10 patients, CSF viral load (VL) was <20 HIV-1 RNA copies/ml at week 52. CSF cell counts and protein levels tended to decrease after 52 weeks of antiretroviral therapy. After 1 year of therapy, 13 of 21 patients (62%) in the double-therapy groups (zidovudine plus lamivudine [n = 9] and stavudine plus lamivudine [n = 12]) had evidence of M184V mutation. None of the 10 samples of patients receiving triple therapy could be amplified because of low HIV RNA levels. The mean increase in CD4 cells at week 52 was greater in the stavudine and lamivudine and indinavir group than in the double-treatment arms (186 versus 67 and 102, respectively; p =.03). In patients treated with triple therapy, the increase in naive T cells (CD4 and CD8) was greater than in patients treated with double therapy. Markers of activation decreased further in patients treated with the regimen that included protease inhibitors. Proliferative responses to HIV-1 p24 antigen were never recovered after double or triple therapy. Our study suggests that even in very early stages of HIV-1 disease only therapy with two NRTIs and one protease inhibitor reduces plasma, lymphoid tissue, and CSF VL to undetectable levels. HIV-1-related immune system abnormalities improved but were still defective after 1 year of antiretroviral therapy.

Adult↗

Phase I-II trial evaluating combined intensity-modulated radiotherapy and in situ gene therapy with or without hormonal therapy in treatment of prostate cancer-interim report on PSA response and biopsy data.

PURPOSE: There is an evolving role for combining radiotherapy (RT) with gene therapy in the management of prostate cancer. However, the clinical results of this combined approach are much needed. The preliminary results addressing the safety of this Phase I-II study combining RT and gene therapy (adenovirus/herpes simplex virus-thymidine kinase gene/valacyclovir with or without hormonal therapy) in the treatment of prostate cancer have been previously reported. We now report the prostate-specific antigen (PSA) response and biopsy data. METHODS AND MATERIALS: This trial was composed of three separate arms. Arm A consisted of low-risk patients (Stage T1-T2a, Gleason score <7, pretreatment PSA <10 ng/mL) treated with combined RT-gene therapy. A mean dose of 76 Gy was delivered to the prostate with intensity-modulated RT. They also received adenovirus/herpes simplex virus-thymidine kinase/valacyclovir gene therapy. Arm B consisted of high-risk patients (Stage T2b-T3, Gleason score >6, pretreatment PSA level >10 ng/mL) treated with combined RT-gene therapy and hormonal therapy (luteinizing hormone-releasing hormone agonist [30-mg Lupron, 4-month depot] and an antiandrogen [flutamide, 250 mg t.i.d. for 14 days]). Arm C consisted of patients with Stage D1 (positive pelvic lymph nodes) who received the same regimen as Arm B with the addition of 45 Gy to the pelvic lymphatics. PSA determination and biopsy were performed before, during, and after treatment. The American Society for Therapeutic Radiology and Oncology consensus definition (three consecutive rises in PSA level) was used to denote PSA failure. RESULTS: Fifty-nine patients (29 in Arm A, 26 in Arm B, and 4 in Arm C) completed the trial. The median age was 68 years (range, 39-85 years). The median follow-up for the entire group was 13.5 months (range, 1.4-27.8 months). Only Arm A patients were observed to have an increase in PSA on Day 14. The PSA then declined appropriately. All patients in Arm A (median follow-up, 13.4 months) and Arm B (median follow-up, 13.9 months) had biochemical control at last follow-up. Three patients in Arm C (with pretreatment PSA of 335, 19.6, and 2.5 ng/mL and a combined Gleason score of 8, 9, and 9 involving all biopsy cores) had biochemical failure at 3, 3, and 7.7 months. Two patients had distant failure in bone and 1 patient in the para-aortic lymph nodes outside the RT portal. Six to twelve prostate biopsies performed in these 3 patients revealed no evidence of residual carcinoma. In Arm A, biopsy showed no evidence of carcinoma in 66.7% (18 of 27), 92.3% (24 of 26), 91.7% (11 of 12), 100% (8 of 8), and 100% (6 of 6) at 6 weeks, 4 months, 12 months, 18 months, and 24 months after treatment, respectively. In Arm B, no evidence of carcinoma on biopsy was noted in 96% (24 of 25), 90.5% (19 of 21), 100% (14 of 14), 100% (7 of 7), and 100% (2 of 2), respectively, in the same interval after treatment. CONCLUSION: This is the first reported trial of its kind in the field of prostate cancer that aims to expand the therapeutic index of RT by combining it with in situ gene therapy. The initial transient PSA rise in the Arm A patients may have been a result of local immunologic response or inflammation elicited by in situ gene therapy. Additional investigation to elucidate the mechanisms is needed. Hormonal therapy may have obliterated this rise in Arm B and C patients. The biopsy data were encouraging and appeared to show no evidence of malignancy earlier than historical data. Combined RT, short-course hormonal therapy, and in situ therapy appeared to provide good locoregional control but inadequate systemic control in patients with positive pelvic lymph nodes. Longer term use of hormonal therapy in addition to gene therapy and RT has been adopted for this group of patients to maximize both locoregional and systemic control.

Acyclovir↗

Efficacy and toxicity of replication-competent adenovirus-mediated double suicide gene therapy in combination with radiation therapy in an orthotopic mouse prostate cancer model.

PURPOSE: The purpose of this study was to evaluate the efficacy and toxicity of replication-competent adenovirus-mediated double suicide gene therapy in an adjuvant setting with external beam radiation therapy (EBRT) in an experimental prostate cancer model in preparation for a Phase I clinical study in humans. METHODS: For efficacy studies, i.m. DU145 and intraprostatic LNCaP C4-2 tumors were established in immune-deficient mice. Tumors were injected with the lytic, replication-competent Ad5-CD/TKrep adenovirus containing a cytosine deaminase (CD)/herpes simplex virus thymidine kinase (HSV-1 TK) fusion gene. Two days later, mice were administered 1 week of 5-fluorocytosine + ganciclovir (GCV) prodrug therapy and fractionated doses of EBRT (trimodal therapy). Tumor control rate of trimodal therapy was compared to that of EBRT alone. For toxicology studies, immune-competent male mice received a single intraprostatic injection (10(10) vp) of the replication-competent Ad5-CD/TKrep adenovirus. Two days later, mice were administered 4 weeks of 5-fluorocytosine + GCV prodrug therapy and 56 Gy EBRT to the pelvic region. The toxicity of trimodal therapy was assessed by histopathologic analysis of major organs and clinical chemistries. RESULTS: In both the i.m. DU145 and intraprostatic LNCaP C4-2 tumor models, trimodal therapy significantly improved primary tumor control beyond that of EBRT alone. In the DU145 model, trimodal therapy resulted in a tumor growth delay (70 days) that was more than twice that (32 days) of EBRT alone. Whereas EBRT failed to eradicate DU145 tumors, trimodal therapy resulted in 25% tumor cure. In the LNCaP C4-2 tumor model, EBRT slowed the growth of intraprostatic tumors, but resulted in no tumor cures, and 57% of the mice developed retroperitoneal lymph node metastases at 3 months. By contrast, trimodal therapy resulted in 44% tumor cure and reduced significantly the percentage (13%) of lymph node metastases relative to EBRT alone. Overall, trimodal therapy was associated with little toxicity. A comparison of the major histopathologic findings among the treatment groups indicated that most of the locoregional (prostate, seminal vesicles, urinary bladder) pathology was attributable to the combined effects of the Ad5-CD/TKrep vector and EBRT and that the prodrugs contributed little to this effect. Importantly, trimodal therapy did not exacerbate inflammation of the rectum and intestines beyond that of EBRT alone. CONCLUSION: Together, the results support the thesis that replication-competent adenovirus-mediated double suicide gene therapy may be a safe and effective adjuvant to EBRT and provide a sound scientific rationale for human trials.

Adenoviridae↗

Long-term outcome of cognitive behavior therapy versus relaxation therapy for chronic fatigue syndrome: a 5-year follow-up study.

OBJECTIVE: This study evaluated the long-term outcome of cognitive behavior therapy versus relaxation therapy for patients with chronic fatigue syndrome. METHOD: Sixty patients who participated in a randomized controlled trial of cognitive behavior therapy versus relaxation therapy for chronic fatigue syndrome were invited to complete self-rated measures and participate in a 5-year follow-up interview with an assessor who was blind to treatment type. RESULTS: Fifty-three patients (88%) participated in the follow-up study: 25 received cognitive behavior therapy and 28 received relaxation therapy. A total of 68% of the patients who received cognitive behavior therapy and 36% who received relaxation therapy rated themselves as "much improved" or "very much improved" at the 5-year follow-up. Significantly more patients receiving cognitive behavior therapy, in relation to those in relaxation therapy, met criteria for complete recovery, were free of relapse, and experienced symptoms that had steadily improved or were consistently mild or absent since treatment ended. Similar proportions were employed, but patients in the cognitive behavior therapy group worked significantly more mean hours per week. Few patients crossed the threshold for "normal" fatigue, despite achieving a good outcome on other measures. Cognitive behavior therapy was positively evaluated and was still used by over 80% of the patients. CONCLUSIONS: Cognitive behavior therapy for chronic fatigue syndrome can produce some lasting benefits but is not a cure. Once therapy ends, some patients have difficulty making further improvements. In the future, attention should be directed toward ensuring that gains are maintained and extended after regular treatment ends.

Activities of Daily Living↗

Radiation therapy combined with hormone therapy for prostate cancer.

Standard-dose radiation therapy has limited capacity to cure bulky and locally advanced prostate cancer. Multiple randomized trials have shown a clinical benefit to adding androgen suppression therapy to external-beam radiation therapy in several subsets of prostate cancer. These studies have made combining hormonal therapy with radiation therapy the standard of care for men with locally advanced (T3-4) and unfavorable prostate cancers (Gleason score >or=8 and/or prostate-specific antigen >20 ng/mL). The clinical impact of hormonal therapy has been seen in biochemical control, local control, distant metastases, disease-specific survival, and overall survival. If hormonal therapy is to be combined with radiation, it should be initiated before the start of radiation and continued during the radiation course rather than used only in the adjuvant setting. Typically, shorter-term hormone therapy is defined as regimens of 4 to 6 months, with longer-term hormone therapy describing durations beyond 24 months. Historically, longer-term hormone therapy was thought to have a more profound systemic effect; however, with the emerging use of hormonal therapy for less-advanced disease, the overall impact of shorter-course hormone therapy is being seen. This review will summarize trials using hormonal therapy and radiation with an emphasis on phase III studies and describe the more recent integration of hormone therapy with radiation for prostate cancer.

Androgen Antagonists↗

Maggot therapy for treating diabetic foot ulcers unresponsive to conventional therapy.

OBJECTIVE: To assess the efficacy of maggot therapy for treating foot and leg ulcers in diabetic patients failing conventional therapy. RESEARCH DESIGN AND METHODS: Retrospective comparison of changes in necrotic and total surface area of chronic wounds treated with either maggot therapy or standard (control) surgical or nonsurgical therapy. RESULTS: In this cohort of 18 patients with 20 nonhealing ulcers, six wounds were treated with conventional therapy, six with maggot therapy, and eight with conventional therapy first, then maggot therapy. Repeated measures ANOVA indicated no significant change in necrotic tissue, except when factoring for treatment (F [1.7, 34] = 5.27, P = 0.013). During the first 14 days of conventional therapy, there was no significant debridement of necrotic tissue; during the same period with maggot therapy, necrotic tissue decreased by an average of 4.1 cm(2) (P = 0.02). After 5 weeks of therapy, conventionally treated wounds were still covered with necrotic tissue over 33% of their surface, whereas after only 4 weeks of therapy maggot-treated wounds were completely debrided (P = 0.001). Maggot therapy was also associated with hastened growth of granulation tissue and greater wound healing rates. CONCLUSIONS: Maggot therapy was more effective and efficient in debriding nonhealing foot and leg ulcers in male diabetic veterans than was continued conventional care.

Aged↗

Pre-operative GnRH analogue therapy before hysterectomy or myomectomy for uterine fibroids.

BACKGROUND: Uterine fibroids, smooth muscle tumours of the uterus, are found in at least 25 to 35% of women over the age of 35 years. Although some of these tumours are asymptomatic, up to 50% cause symptoms severe enough to warrant therapy and surgery is the standard treatment. Fibroid growth is stimulated by oestrogen and gonadotropin releasing hormone agonists (GnRHa) which induce a state of hypoestrogenism have been investigated as a potential treatment. GnRHa treatment causes fibroids to shrink but cannot be used long term because of unacceptable symptoms and bone loss. Therefore, GnRHa may be useful pre-operatively both to reduce fibroid and uterine volume and control bleeding. OBJECTIVES: The objective of this review is to evaluate the role of pre-treatment with gonadotropin releasing hormone (GnRH) analogues prior to a major surgical procedure, either hysterectomy or myomectomy, for uterine fibroids. SEARCH STRATEGY: Electronic searches for relevant randomised controlled trials of the Cochrane Menstrual Disorders and Subfertility Group Register of Trials, MEDLINE, EMBASE, PsychLIT, Current Contents, Biological Abstracts, Social Sciences Index and CINAHL were performed. Attempts were also made to identify trials from citation lists of review articles. In most cases, the first author of each included trial was contacted for additional information. SELECTION CRITERIA: The inclusion criteria were randomised comparisons of GnRH analogue treatment versus placebo, no treatment, or other medical therapy prior to surgery, either myomectomy or hysterectomy, for uterine fibroids. DATA COLLECTION AND ANALYSIS: Nineteen RCTs were identified that fulfilled the inclusion criteria for this review. The reviewers extracted the data independently and odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes were estimated from the data of twelve trials where GnRH analogue treatment was compared with no pre-treatment and five trials where GnRH analogue treatment was compared with placebo (two trials are awaiting assessment). No RCTs of GnRH analogue treatment versus other medical therapy were identified. Results from pre-operative outcomes were combined for both types of surgery but results from intra- and post-operative outcomes were reported separately for myomectomy and hysterectomy. Subgroup analysis was performed according to type of control group, no pre-treatment or placebo, and for some outcomes there were additional subgroup analyses according to size of the uterus in gestational weeks. MAIN RESULTS: Pre- and post-operative haemoglobin (Hb) and haematocrit (HCT) were significantly improved by GnRH analogue therapy prior to surgery, and uterine volume, uterine gestational size and fibroid volume were all reduced. Pelvic symptoms were also reduced but some adverse events were more likely during GnRH analogue therapy. Hysterectomy appeared to be easier after pre-treatment with GnRH analogue therapy; there was reduced operating time and a greater proportion of hysterectomy patients were able to have a vaginal rather than an abdominal procedure. Duration of hospital stay was also reduced. Blood loss and rate of vertical incisions were reduced for both myomectomy and hysterectomy. Evidence of increased risk of fibroid recurrence after GnRH analogue pre-treatment in myomectomy patients was equivocal and no data were available to assess change in post-operative fertility. The increased costs associated with GnRH analogue therapy were not assessed. REVIEWER'S CONCLUSIONS: The use of GnRH analogues for 3 to 4 months prior to fibroid surgery reduce both uterine volume and fibroid size. They are beneficial in the correction of pre-operative iron deficiency anaemia, if present, and reduce intra-operative blood loss. If uterine size is such that a mid-line incision is planned, this can be avoided in many women with the use of GnRH analogues. For patients undergoing hysterectomy, a vaginal procedure is more like

Antineoplastic Agents, Hormonal↗

Primary radiotherapy in the treatment of stage I and II oral tongue cancers: importance of the proportion of therapy delivered with interstitial therapy.

From January 1963 through December 1979, 103 patients with Stage T1N0 and T2N0 squamous cell carcinomas of the oral tongue were treated with definitive radiotherapy. The primary was Stage T1 in 18 patients and T2 in 85 patients. Therapy to the primary consisted of interstitial therapy only in 18 patients, 16-37 Gy in 2.4-4.0 Gy fractions followed by interstitial therapy to doses of 38-55 Gy in 31 patients, external therapy of 40-50 Gy with interstitial therapy of 20-40 Gy in 46 patients, and external beam only to doses of 45-82 Gy in 8 patients. Follow-up ranged from 2 to 290 months (median 159 months). Five of the 8 patients treated with external therapy alone and 6 of the 18 patients treated with interstitial therapy failed at the primary site. In those patients treated with a combination of external and interstitial therapy the 2-year local control rate was 92% for patients treated with external therapy to doses of less than 40 Gy combined with a moderately high dose of brachytherapy, compared with 65% for patients who received external therapy to doses of greater than or equal to 40 Gy with lower brachytherapy doses (p = .01). Conversely the risk of failure in the neck was directly related to the dose delivered by external beam therapy. In field recurrence occurred in 44% of patients receiving no therapy to the neck. 27% in those receiving less than 40 Gy, and 11% in those patients with neck treatment to greater than or equal to 40 Gy. Eleven of 87 (13%) of patients who were at risk for complications for greater than or equal to 24 months developed severe complications; severe complications were more likely to occur in the group who received most of their therapy with external beam irradiation. These data show that a high dose of interstitial therapy is necessary to secure optimum local control of early primary tongue cancer. Because of the high frequency of moderate to severe late complications in this series we have adopted a policy of initial surgery for most oral tongue cancers with postoperative radiotherapy if indicated by pathological features predictive of a high rate of local-regional failure.

Adult↗

Different survival determinants of metastatic breast cancer patients treated with endocrine therapy or chemo-endocrine therapy.

Female patients (n=371) with metastatic breast cancer were treated with endocrine or chemoendocrine therapy as the first-line treatment. Clinical prognostic factors for response and survival were compared between the treatments, including age of the patients, menopausal status, estrogen receptor (ER), disease-free interval (DFI), dominant site of metastasis, number of metastatic organs, performance status (PS), and prior therapy. Although a significantly higher response rate was obtained by the chemo-endocrine therapy compared with the endocrine therapy, the median survival time of patients in endocrine therapy was much longer than those in chemo-endocrine therapy. Multivariate analyses with the logistic regression model showed that in women treated with endocrine therapy ER was shown to be the sole determinant for response, while PS and dominant site of metastasis were selected to be influential in chemotherapy group. For overall survival, the Cox proportional hazard model analysis showed that by endocrine therapy, ER and dominant site were significant determinants of survival, but that of chemotherapy the survival was determined by PS, dominant site, and age of the patients. When response to therapy was included in the Cox survival analysis at the time of 3-month after therapy in the landmark method, the response was the most important factor for survival in both treatment groups, however dominant site in endocrine therapy, and dominant site, PS, and age in chemo-endocrine therapy significantly modified survival. It is concluded that endocrine therapy and chemo-endocrine therapy have different determinants for response and survival in metastatic breast cancer, and that in the survival analysis treatment modality should be included as a prognostic factor.

Adult↗

[Preliminary clinical evaluation of continuous infusion of 5-FU and low-dose Cisplatin (LFP) therapy alone and combined with radiation therapy for treatment of advanced or recurrent esophageal cancer].

We evaluated the clinical effect of 5-FU and low-dose Cisplatin (LFP) therapy alone and LFP therapy combined with radiation therapy in patients with advanced or recurrent esophageal cancer. From March 1995 to September 2000, 11 patients with inoperable esophageal cancer, 8 patients with adjuvant chemotherapy post operation, and 14 patients with recurrent esophageal cancer were treated with LFP therapy. 5-FU (160 mg/m2/day) was continuously infused over 24 hours, and CDDP (3-7 mg/m2/day) was infused for 30 minutes. The administration schedule consisted of 5-FU for 7 consecutive days and CDDP for 5 days followed by a 2-day rest, each for four weeks. We combined radiation therapy for the patients with all lesions that could be included in the radiation field. Of 30 patients with measurable lesions the response rates of LFP therapy alone and LFP therapy combined with radiation therapy were 33% and 60%, respectively. Toxicity over grade 3 appeared in 3 of 15 patients with LFP therapy combined with radiation therapy. There was no significant difference between LFP therapy alone and LFP therapy combined with radiation therapy with regard to survival rate of inoperable and recurrent esophageal cancer. In conclusion, LFP therapy alone may be effective for esophageal cancer.

Aged↗

Radiation therapy in management of carcinoma of the vulva with emphasis on conservation therapy.

BACKGROUND: This report consists of a retrospective analysis of 50 patients with primary invasive and 17 with recurrent histologically confirmed vulvar carcinoma treated with radiation therapy for locoregional disease. METHODS: Of the patients with primary tumors, 13 were treated with wide local excision plus radiation therapy; 13 had radical vulvectomy followed by irradiation to the operative fields and inguinal-femoral/pelvic lymph nodes; 8 received similar postoperative radiation therapy after partial or simple vulvectomy; 16 patients had radiation therapy alone after biopsy; and 17 had recurrent tumors treated with radiation therapy alone. RESULTS: In patients treated with biopsy/local excision, local tumor control was 92-100% in T1-3N0 disease, 40% in similar stages with N1-3, and 27% in recurrent tumors. Among patients treated with partial/radical vulvectomy and radiation therapy, primary tumor control was 90% in those with T1-3 tumors and any nodal stage, 33% in those with any T stage and N3 lymph nodes, and 66% in patients with recurrent tumors. The actuarial 5-year disease-free survival rates were 87% for patients with T1N0 disease, 62% for those with T2-3N0 disease, 30% for those with T1-3N1 disease, and 11% for patients with recurrent tumors; there were no long-term survivors with T4 or N2-3 disease. Four of 17 patients treated for postvulvectomy recurrent disease remain disease-free after local tumor excision and radiation therapy. In patients with T1-2 tumors treated with biopsy/wide tumor excision and radiation therapy with doses less than 50 Gy, the local tumor control was 75% (three of four patients), in contrast to 100% (13 of 13 patients) with 50.01-65 Gy. With T3-4 tumors treated with local excision and radiation therapy, tumor control occurred in none of three patients with doses less than 50 Gy and 66% (six of nine) with 50.01-65 Gy. In patients with T1-2 tumors treated with partial/radical vulvectomy and radiation therapy, local tumor control was 75% (six of eight), regardless of dose level; in T3-4 tumors, it was 67% (four of six patients) with 50-60 Gy and 86% (six of seven) with 65-70 Gy. Differences were not statistically significant. There was no significant dose response for tumor control in the inguinal-femoral lymph nodes, with doses of 50 Gy being adequate for elective treatment of nonpalpable lymph nodes and 60-70 Gy controlling tumor growth in 75-80% of patients with N2-3 nodes when administered postoperatively, after partial or radical lymph node dissection. Significant treatment morbidity included one rectovaginal fistula, one case of proctitis, one rectal stricture, four bone/skin necroses, four vaginal necroses, and one groin abscess. CONCLUSIONS: Wide local tumor excision and radiation therapy or irradiation alone in T1-2 tumors is an alternative treatment to radical vulvectomy in controlling vulvar carcinoma, with significantly less morbidity. In comparison with reported rates for surgery alone, radiation therapy after radical vulvectomy for locally advanced tumors improves tumor control at the primary site and regional lymphatics. Indications and techniques of radiation therapy are discussed.

Adenocarcinoma↗

Outpatient treatment of moderately severe active ulcerative colitis with pulsed steroid therapy and conventional steroid therapy.

Pulsed steroid therapy may induce rapid remission in patients with moderately severe ulcerative colitis in outpatient clinics. A total of 19 patients with moderately severe active ulcerative colitis who refused hospitalization were treated between October 1999 and September 2001 in the outpatient clinic. Patients were treated with either conventional oral steroid therapy or intravenous pulsed steroid therapy followed by conventional oral steroid therapy. Eight patients received conventional steroid therapy and 11 patients received pulsed steroid therapy followed by conventional steroid therapy. The efficacies of the two types of steroid therapy were equal, but patients with active colitis responded more quickly to pulsed steroid therapy than to conventional steroid therapy. No serious adverse effects were observed. Moderately severe colitis can be safely treated with either conventional or pulsed steroid therapy in the outpatient clinic, but pulsed steroid therapy may induce clinical remission more quickly than conventional steroid therapy.

Administration, Oral↗

Pretreatment with Lactobacillus- and Bifidobacterium-containing yogurt can improve the efficacy of quadruple therapy in eradicating residual Helicobacter pylori infection after failed triple therapy.

BACKGROUND: Lactobacillus- and Bifidobacterium-containing yogurt (AB-yogurt) can suppress Helicobacter pylori. Improvement of the eradication rate by quadruple therapy of residual H. pylori after failed triple therapy is needed. OBJECTIVE: We tested whether prior treatment with AB-yogurt improved the efficacy of quadruple therapy in eradicating residual H. pylori after failed triple therapy. DESIGN: One hundred thirty-eight patients in whom triple therapy failed were enrolled for a culture study of H. pylori to assess antimicrobial resistance. These patients were then randomly assigned in equal numbers to either a yogurt-plus-quadruple therapy group or a quadruple therapy-only group. The patients received 1 wk of quadruple therapy with or without a 4-wk pretreatment with AB-yogurt (400 mL/d). In the yogurt-plus-quadruple group, excessive delta(13)CO(2)/mL values of the (13)C-urea breath test were collected before and every 2 wk during the 4-wk ingestion of yogurt. For both groups, a (13)C-urea breath test was conducted > or =6 wk after the quadruple therapy to assess the outcome of residual H. pylori eradication. RESULTS: For the patients in the yogurt-plus-quadruple therapy group infected with either antibiotic-sensitive or -resistant H. pylori, the excessive delta(13)CO(2)/mL values of the (13)C-urea breath test were significantly decreased after the 4-wk ingestion of AB-yogurt (P < 0.0001). The yogurt-plus-quadruple therapy group had a higher H. pylori eradication rate than did the quadruple therapy-only group (intention-to-treat analysis: 85% compared with 71.1%, P < 0.05; per-protocol analysis: 90.8% compared with 76.6%, P < 0.05). CONCLUSION: A 4-wk pretreatment with AB-yogurt can decrease H. pylori loads despite antimicrobial resistance, thus improving the efficacy of quadruple therapy in eradicating residual H. pylori.

Anti-Bacterial Agents↗

The effectiveness of psychodynamic therapy and cognitive behavior therapy in the treatment of personality disorders: a meta-analysis.

OBJECTIVE: The authors conducted a meta-analysis to address the effectiveness of psychodynamic therapy and cognitive behavior therapy in the treatment of personality disorders. METHOD: Studies of psychodynamic therapy and cognitive behavior therapy that were published between 1974 and 2001 were collected. Only studies that 1) used standardized methods to diagnose personality disorders, 2) applied reliable and valid instruments for the assessment of outcome, and 3) reported data that allowed calculation of within-group effect sizes or assessment of personality disorder recovery rates were included. Fourteen studies of psychodynamic therapy and 11 studies of cognitive behavior therapy were included. RESULTS: Psychodynamic therapy yielded a large overall effect size (1.46), with effect sizes of 1.08 found for self-report measures and 1.79 for observer-rated measures. For cognitive behavior therapy, the corresponding values were 1.00, 1.20, and 0.87. For more specific measures of personality disorder pathology, a large overall effect size (1.56) was seen for psychodynamic therapy. Two cognitive behavior therapy studies reported significant effects for more specific measures of personality disorder pathology. For psychodynamic therapy, the effect sizes indicate long-term rather than short-term change in personality disorders. CONCLUSIONS: There is evidence that both psychodynamic therapy and cognitive behavior therapy are effective treatments of personality disorders. Since the number of studies that could be included in this meta-analysis was limited, the conclusions that can be drawn are only preliminary. Further studies are necessary that examine specific forms of psychotherapy for specific types of personality disorders and that use measures of core psychopathology. Both longer treatments and follow-up studies should be included.

Cognitive Behavioral Therapy↗