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The epidemiology of inflammatory bowel disease: a large, population-based study in Sweden.

Previous population-based incidence studies of inflammatory bowel disease are limited by small numbers, short duration, or inadequate case-finding. To address these problems, we identified all persons with confirmed ulcerative colitis (n = 2509) or Crohn's disease (n = 1469) in the Uppsala Health Care Region from 1965 to 1983. Age-specific incidence rates by sex were slightly greater for males with ulcerative colitis and females with Crohn's disease. Incidence rates for ulcerative colitis and Crohn's disease were higher in urban than rural areas. The annual incidence rate of ulcerative colitis increased from less than 7 per 100,000 to more than 12 per 100,000 during the study period, while the rate for Crohn's disease remained between 5 and 7 per 100,000. The increase in the incidence of ulcerative colitis was the result of a marked increase in the number of patients with ulcerative proctitis. Analyses by 5-year birth cohorts suggest that those born from 1945 through 1954 were at higher risk for ulcerative colitis and Crohn's disease, and that this effect was accounted for by those born in the first half of the year. The seasonality in the cohort effect, combined with the urban preponderance of disease, suggests that environmental causes may be involved in ulcerative colitis and Crohn's disease.

Adolescent↗

Survival and causes of death in patients with inflammatory bowel disease: a population-based study.

Relative survival up to December 31, 1986 was analyzed for all patients diagnosed with ulcerative colitis (UC) (n = 2,509) and Crohn's disease (CD) (n = 1,469) within the Uppsala Region, Sweden 1965-1983. After 10 years survival was 96% of that expected for UC and CD. Patients with ulcerative proctitis, left-sided colitis, and pancolitis at diagnosis had relative survival rates of 98%, 96%, and 93% respectively. Survival did not differ by extent at diagnosis for patients with CD. After including prevalent cases, 684 deaths occurred compared with 481.1 expected deaths [standardized mortality ratio (SMR) = 1.4; 95% confidence interval (CI) = 1.3-1.5]. Inflammatory bowel disease was the main reason for this excess mortality. Colorectal cancer increased mortality (50 deaths observed vs. 15.2 expected). Death from other cancers were not greater than expected. Obstructive respiratory diseases, especially bronchitis, emphysema, and asthma increased mortality SMR = 1.5 (95% CI = 1.1-2.2) in UC. Cerebrovascular disease mortality occurred less often than expected (SMR = 0.7; 95% CI = 0.5-1.0). Mortality for other diseases and groups of diseases was close to that expected.

Cause of Death↗

Radiotherapy of primary carcinoma of the vagina: management and results of different therapy schemes.

Three hundred and sixty-two cases of primary vaginal carcinoma were treated at the Irradiation Department of the University Clinic for Obstetrics and Gynecology, Vienna, from 1950 to 1977. As the method of choice an individually dosed, fractioned, and protracted radium-telecobalt therapy was employed. Comparing the last period analyzed (1971-1977) with another period 20 years earlier (1951-1956), a marked increase of advanced stages and older patients can be observed. These changes are reflected in the 5-year remission rate: in the total population it was 39.8%, as compared to 32% for the period from 1971 to 1977. For a group of 99 patients, who were treated between 1971 and 1977, the therapeutic effect of different therapy schemes is reported. The benefit of teletherapy is remarkable for advanced states, whereas for stages I and II an intrauterine application may be of importance. The complication rate amounted to 8% recto- or vesicovaginal fistulas and 41% and 43% cystitis and proctitis. The central importance of gynecological screening, especially for older women, is emphasized.

Adult↗

Correlations of dose and time-dose-fractionation factors (TDF) with treatment results and side effects in cancer of the uterine cervix.

Treatment results and side effects were analyzed for 57 patients with stage IB-IIIA cancer of the uterine cervix who received external beam radiotherapy combined with intracavitary insertion of cesium-137 sources. The total dosage and time-dose-fractionation (TDF) factors were calculated at point A and at points of maximum exposure in the rectum and bladder. The overall 5-year survival was 62%, and 78% of the complete responders were free of disease at 5 years. A total of 12 patients (21%) developed rectal complications. Two patients (4%) had rectal fibrosis and proctitis; seven cases of rectal bleeding occurred (12%), and 3 patients (5%) developed rectovaginal fistulas. There was no correlation between dose and TDF at point A and treatment failure or appearance of rectal complications. However, the occurrence of radiation damage in the rectum was consistently associated with high values of TDF when they were calculated in the region of maximal exposure in the rectum. The results suggest that TDF may be a useful parameter for predicting radiation damage in combined external beam and intracavitary treatment of cervical cancer.

Female↗

The treatment of stage III carcinoma of the uterine cervix with telecobalt irradiation.

This is a retrospective analysis of 148 patients with histologically proven carcinoma of the cervix, stage III, treated with irradiation. All patients received external irradiation with cobalt 60 followed by intracavitary radium application. The median age was 55 years. Squamous cell carcinoma was found in 96.5% of the cases. The 8-year actuarial survival rate was 41%. Bilateral parametrial invasion proved to be a strong prognostic factor. Patients with unilateral disease had a survival rate of 43% whereas in those with bilateral involvement it was only 15% (P less than 0.005). The total pelvic failure rate was 29.5%. The overall incidence of distant metastasis was 11%. The complication rate (minor and major complications) was high, with vaginal stenosis (22.5%), proctitis (21.5%), cystitis (13.5%), and fistulae (4%) occurring in 33, 32, 20, and 6 patients, respectively. New treatment modalities are urgently needed for advanced carcinoma of the cervix. Bilateral parametrial involvement is an unfavorable prognostic factor and this should be kept in mind when designing new protocols.

Adult↗

Randomized study of preoperative radiation and surgery or irradiation alone in the treatment of stage IB and IIA carcinoma of the uterine cervix: final report.

A prospective randomized study in selected patients with Stage IB and IIA carcinoma of the uterine cervix was carried out at Washington University between January 1966 and December 1979. Patients were randomized to be treated with irradiation alone consisting of 1000 cGy whole pelvis, additional 4000 cGy to the parametria with a step wedge midline block, and two intracavitary insertions for 7500 mgh; or irradiation and surgery, consisting of 2000 cGy whole pelvis irradiation, one intracavitary insertion for 5000-6000 mgh followed 2 to 6 weeks later by a radical hysterectomy with pelvic lymphadenectomy. A total of 40 patients with Stage IB and 16 with Stage IIA were randomized to be treated with irradiation alone. A similar group of 48 patients with Stage IB and 14 with IIA were randomized to the preoperative radiation and surgery group. The 5-year, tumor-free actuarial survival for Stage IB patients treated with radiation was 89% and with preoperative radiation and surgery 80%. In Stage IIA, the tumor-free actuarial 5-year survival was 56% for the irradiation alone group and 79% for the patients treated with preoperative radiation and radical hysterectomy. In the patients with Stage IB treated by irradiation alone only one pelvic failure combined with distant metastasis occurred, and 3 patients developed distant metastasis. In the 48 patients treated with combined therapy, there were six pelvic failures (12.5%) all combined with distant metastases and two distant metastases alone. In the 16 patients with Stage IIA treated with radiotherapy alone, there were four pelvic failures (all parametrial), three of them combined with distant metastasis. In the 14 patients treated with irradiation and surgery, two developed a pelvic recurrence, and one distant metastasis. In the preoperative radiation group, the incidence of metastatic pelvic lymph nodes was 6.3% in Stage IB and 7.1% in Stage IIA. Major complications of therapy in the patients treated with radiation alone (10%) consisted of one rectovaginal fistula, two vesicovaginal fistulas, and one rectal stricture. In the preoperative radiation group, three ureteral strictures and two severe proctitis-rectal strictures were noted (8%). The present study shows no significant difference in therapeutic results or morbidity for invasive carcinoma of the uterine cervix Stage IB or IIA treated with irradiation alone or combined with a radical hysterectomy and lymphadenectomy.

Carcinoma↗

Concurrent radiation and chemotherapy in vulvar carcinoma.

Between June 1984 and February 1988 the role of radiation with concurrent infusional 5-fluorouracil with or without mitomycin C (CT-RT) was examined in 33 patients with vulvar cancer. The median duration of follow-up is 16 months (range 5 to 45 months). Nine received adjuvant postsurgical CT-RT and none has relapsed in the radiation field. Seven are alive disease free. Two have died of distant metastases. Of the 9 receiving definitive primary CT-RT, 6 had initial complete response with subsequent vulvar relapse developing in 3. Seven of the 9 remain disease free after CT-RT alone (in 3) or with the addition of a local excision of residual or recurrent disease (in 6). One patient did not respond to CT-RT and required a radical vulvectomy and groin node dissection. Fifteen received CT-RT for disease recurrence following primary surgery. Disease was present in the vulva only in 11, vulva and inguinal nodes in 1 and nodes only in 3. Eight of the 15 had a complete response and no relapses occurred in the treated sites. Four of the 8 dying of disease developed pulmonary metastases. Serious late complications developed in 2 patients, 1 avascular hip necrosis and 1 proctitis requiring a defunctioning colostomy. CT-RT appears tolerable and may contribute to enhanced locoregional control in recurrent or advanced disease. As initial therapy it may allow lesser surgery with preservation of normal anatomy in selected primary vulvar cancers.

Adenocarcinoma↗

Extraperitoneal versus transperitoneal selective paraaortic lymphadenectomy in the pretreatment surgical staging of advanced cervical carcinoma (a Gynecologic Oncology Group study).

Two-hundred and eighty-eight patients with predominately stage IIB or IIIB cervical carcinoma underwent pretreatment surgical staging including selective paraaortic lymphadenectomy (SPAL), followed by pelvic irradiation with or without paraaortic irradiation (RT). Four patients were excluded from analysis (two received no RT and two were insufficiently documented). Of the remaining 284 patients, 128 underwent extraperitoneal (EP) SPAL and 156 transperitoneal (TP) SPAL procedures. Age, race, and stage (clinical and surgical), cell type, paraaortic nodal status, and peritoneal cytology findings were similar in both groups. Complications presumed to arise from operative staging were infection, which was similar for both groups, and vascular injury, which was higher in the TP group, although not statistically significant. Complications subsequent to RT fell into two categories: local-pelvic necrosis, vesicovaginal and rectovaginal fistulas, proctitis, etc., and regional-enterovaginal fistula, bowel obstruction, enteritis, bowel perforation, etc. The frequency of local complications was similar for both EP and TP patients. Utilizing univariant analysis, among regional complications, both bowel obstruction and nonobstructive enteric injuries were observed significantly more often in TP patients than in EP patients (11.5% vs 3.9%, P = 0.03, for both types). Multivariant analysis confirmed these observations. This report supports the conclusions that in advanced cervical carcinoma (1) EP- and TP-SPAL are of similar sensitivity in detecting nodal spread, (2) no significant differences in the frequency of surgical complications could be detected between EP- and TP-SPAL groups, and (3) TP-SPAL is associated with a higher frequency of certain postirradiation regional enteric complications.

Adult↗

Carcinoma of the cervical stump.

Treatment, prognosis, and complication rate were retrospectively studied in 46 patients with cervical stump cancer. There were no differences in clinical stage distribution and histopathological findings between these patients and patients with cervical cancer of the intact uterus. However, 43 patients were treated by radiation therapy and only 3 patients had a cervical amputation. The 5-year survival rate was 62%, which is comparable to that of cervical cancers. Late complications were found in 22 patients: 3 (7%) had symptoms of severe radiation reactions of the bladder (necrosis or vesicovaginal fistels), 14 (31%) had severe radiation reactions in the rectum and the sigmoid (severe proctitis, stenosis, or rectovaginal fistels) and 7 (18%) had large vault necrosis. It is concluded that the frequency of cervical stump cancer is low, but cancer in the cervical stump is difficult to treat and the rate of severe late complications is so high that it should be considered when one is deciding between supravaginal and total hysterectomy. Moreover, screening for cervical cancer should be performed regularly after supravaginal hysterectomy.

Adult↗

Male genital Chlamydia trachomatis infections.

The role of Chlamydia trachomatis in infections of the male genital tract is reviewed. The organism is an important cause of non-gonococcal urethritis, post-gonococcal urethritis and epididymitis, but does not appear to play a major part in the pathogenesis of chronic abacterial prostatitis or in proctitis in anoreceptive homosexual men.

Chlamydia Infections↗

Radiation tolerance of the rat rectum to fractionated X-rays and pi-mesons.

A 2.5 cm segment of the rectum of female F344 rats was irradiated with up to 10 fractions of X-rays or pions. Transient signs of acute proctitis were followed by chronic rectal injury starting at about 2 months. Recto-vaginal fistulas were frequently observed in animals with severe chronic injury. Two patterns of chronic injury were observed, an early type consisting of deep ulcers and fistulas, and a late type characterized by vascular injury, fibrosis and mucosal cysts. In a 4-fraction X-ray experiment, the influence of a low-residue diet was compared with a regular diet, showing no significant differences in pathology or survival. Isoeffective doses were determined for the occurrence of severe rectal injury at 250 days. Fitting the data to an LQ-model yielded an alpha/beta ratio of 13 Gy for pions, and 6.5 Gy for X-rays. Increasing the overall treatment time from 9 days to one month gave a significant rise in isoeffective doses for chronic injury. This suggests that the more delayed types of injury did not develop independently from the acute mucosal changes. The RBE of pions for rectal injury at 250 days was 1.2 for single doses, increasing to about 1.4-1.5 at a dose per fraction of 4 Gy. These values are similar to those obtained in other acute and late responding tissues.

Animals↗

Long source-skin distance rectal irradiation technique: a review of results.

PURPOSE: This study reports the clinical outcome of fifteen patients with low rectal adenocarcinoma treated with the long source-skin distance (SSD) of endorectal irradiation technique. This method was designed at McGill University in 1986 as an alternative to the standard short SSD rectal irradiation that was developed by Papillon (Proc. R. Soc. Med. 66: 1179-1181, 1973). METHODS AND MATERIALS: Between April 1986 and May 1993, six females and nine males were treated with this technique. Fourteen patients were treated with curative intent and one woman for palliation. The median total dose was 85 Gy (range 60-135 Gy) in a median of 3 fractions (range 3-5) over a median treatment time of 5 weeks (range 2-9.5 weeks). RESULTS: With a mean follow-up of 39 months and a median of 24 months (range 3 months-8.7 years), actuarial overall survival and disease-free survival rates are 50.8% and 71.4%, respectively, at 8.7 years. No patients have died of recurrent disease, but one patient has distant metastatic disease. One patient treated with curative intent required an abdominoperineal resection for progressive disease. Treatments were tolerated well by all patients. Four patients required steroid enemas for localized proctitis for a short period of time. They all responded well and had complete resolution of symptoms. CONCLUSIONS: Our results are comparable with those in other reports in the literature. The complications are similar in type and frequency to other published series. The long SSD technique may be an acceptable alternative to the standard short SSD technique.

Adenocarcinoma↗

Budesonide in inflammatory bowel disease.

Due to its immunomodulatory and anti-inflammatory properties glucocorticosteroids have proved to be highly efficacious in patients with inflammatory bowel disease. However, because of the risk of side-effects, the dose and duration of therapy with systemically acting glucocorticosteroids have to be restricted. Recently the use of topically acting glucocorticosteroids has attracted great interest. Among the various topically acting glucocorticosteroids budesonide has emerged as the most promising. Budesonide is highly potent, is readily water-soluble and has low systemic bioavailability, thus reducing the risk of corticosteroid-related side-effects. When given as enema to patients with proctitis or proctosigmoiditis, the efficacy of budesonide is greater than that of placebo and equal to that of prednisolone or 5-aminosalicylic acid enemas. In an enteric-coated formulation budesonide is more effective than placebo in achieving and maintaining remission in patients with ileocecal Crohn's disease. Although corticosteroid-related side-effects are rare, some suppression of the hypothalamic-pituitary-adrenal axis may occur.

Administration, Oral↗

Faecal incontinence 1994: which test and which treatment?

Faecal incontinence is a disabling condition caused by: (1) sphincter damage caused by childbirth, anorectal surgery, trauma, fistulae and abscesses; (2) pudendal neuropathy ("idiopathic faecal incontinence") caused by stretch injury by long-standing constipation or prolonged labor; (3) diminished rectal compliance in proctitis, low anterior resection or small pouches; (4) faecal impaction causing paradoxal diarrhoea; (5) neurological disease involving the pelvic floor and or the central nervous system; (6) diarrhoea. Often several factors play a role in a patient. A medical history and physical examination will generally provide a reasonable diagnosis. Anorectal function tests can show one or more abnormalities. Anal manometry can show low sphincter pressures; rectal compliance can show a small rectal volume; anal mucosal sensitivity measurement can show a high threshold and neurophysiological tests can demonstrate diminished muscle activity and a delayed pudendal nerve motor latency. Anal endosonography and defaecography have a direct clinical impact. Anal endosonography is a promising diagnostic tool demonstrating sphincter defects, even those not previously suspected. A sphincter defect demonstrated by anal endosonography provides a solid basis for a sphincter repair. Defaecography can reveal an intussusception, which is an indication for performing a rectopexy in the incontinent patient. A suggested work-up of the incontinent patient is given in a table. Besides the classic surgical treatments such as sphincter repair, rectopexy and post-anal repair new (surgical) options have been tried. The most promising new therapy seems the dynamic gracilis repair.

Fecal Incontinence↗

Custom-made capsules and suppositories of methadone for patients on high-dose opioids for cancer pain.

In a prospective, open study, 37 advanced cancer patients in poor pain control receiving high doses of subcutaneous hydromorphone (mean daily dose: 276 +/- 163 mg) were switched to methadone by use of custom-made capsules (21 patients) or suppositories (16 patients). The change in opioid took place over 6.5 +/- 3.6 days (oral) and 3.2 +/- 2.7 days (rectal). The methadone/hydromorphone dose ratios were 1.2 +/- 1.3 and 3 +/- 2 for the oral and rectal routes, respectively (P = 0.03) as compared to an expected ratio of 5-7, based on single dose available data. Pain intensity (VAS 0-100 mm) and the number of extra doses of analgesic per day were 51 +/- 22 and 3.2 +/- 2.7 with hydromorphone, versus 34 +/- 21 (P < 0.001) and 2.1 +/- 1.9 (P = 0.03) with methadone, respectively. The total cost of treatment was Canadian $148 +/- 202 with methadone as compared to Canadian $2135 +/- 472 with hydromorphone (P < 0.001). Toxicity was limited to mild sedation in all patients and proctitis in 2 patients on suppositories (one of whom required discontinuation of methadone). Plasma levels obtained in 6 patients on suppositories revealed large inter-individual variation in methadone level (ng/ml) to dose (mg/day) ratio (range: 0.8-8.5). Within individuals, the ratio remained constant over a range of doses. We conclude that a slow switch-over to methadone is a safe, effective and low cost alternative in selected cancer patients receiving high doses of opioids for poor prognostic pain syndromes.

Aged↗

The Syed-Neblett interstitial template in locally advanced gynecological malignancies.

Twenty-eight patients with locally advanced malignancies of the cervix and vagina were treated with a combination of external radiation therapy and afterloading Syed-Neblett iridium template. There were 22 patients with squamous cell cancer and two patients with adenocarcinomas of the cervix. Four patients with squamous cell cancer of the vagina were treated with this method. Only patients with locally advanced disease (cervical lesion greater than 4 cm in diameter) and poor vaginal anatomy were selected for this modality of therapy. In our series the incidence of distant failures of 39% seems to confirm the significance of local volume of disease as a prognostic indicator; despite a local control rate of 59%, only 33% of our patients are alive from 25-51 months. Complications occurred in 12 patients (42%). Six patients (22%) developed severe rectal stricture or rectovaginal fistula necessitating diverting sigmoid colostomy; five patients (18%) developed hemorrhagic proctitis with diarrhea and tenesmus; one patient developed vaginal vault necrosis. Complications occurred 7 to 24 months following therapy. Six of the 12 patients developing complications are dead of disease. On the basis of this study and because of the low cure rate and high incidence of complications, the value of the Syed-Neblett template in locally advanced gynecologic malignancies should be reconsidered.

Adenocarcinoma↗

Treatment of advanced cancer of the cervix with transperineal interstitial irradiation.

A pilot study using transperineal interstitial implantation to the parametrium in patients with locally advanced carcinoma of the cervix or with distorted anatomy is presented. Twenty-one consecutive patients (2 cervical stump Stage IB, 3 Stage IIB, 15 Stage IIIB, 1 Stage IVA) received one (12) or two (9) implants following 40-45 Gy whole pelvis external irradiation. In addition 8 patients underwent staging laparotomies concurrently with the first implant procedure. Control of the pelvic tumor was accomplished in 18 of 21 patients (85%) with a mean follow-up of 26 months (range 15 to 48 months). Seven patients (33%) developed long term complications (fistula 3, superficial necrosis of the vagina 1, severe proctitis or cystitis 3). Six of the complications occurred in 8 patients (75%) who had radioactive sources placed on the surface of the vaginal obturator as a substitute for the lack of tandem. In contrast, only 1 in the remaining 13 patients (8%) who did not have obturator sources placed, developed long term complications.

Adult↗

Radiotherapy of carcinoma of the uterine cervix in Singapore, 1973-1975.

The results of 322 patients with uterine cervix carcinoma treated by radiotherapy at the Singapore General Hospital in the 3-year period from 1973 to 75 are presented. Two hundred seventy-nine patients were treated with a combination of intracavitary radium, using Fletcher-Suit applicators and cobalt teletherapy; the remaining 43 patients received only cobalt teletherapy. One hundred thirty-four patients (41.6%) presented with FIGO Stage III disease. Only 46 patients (14.3%) presented with Stage I disease, showing that patients tended to present late in the disease course. Five-year actuarial (uncorrected) survival rates of 86.7% for Stage I, 65.0% for Stage II, 41.4% for Stage III and 4.9% for Stage IV were obtained with corresponding 10 year rates of 79.6%, 60.2%, 35.2% and 0%. The overall 5 and 10 year survival rates were 54.0% and 48.2%, respectively. The survival rates "flattened off" at about 7-8 years, reflecting late deaths after the fifth anniversary of treatment. Non-severe complications consisted mainly of chronic proctitis (41.3%) and vaginal stenosis (20.8%). Major complications were intestinal stricture (1.2%) and fistula formation (1.6%).

Adult↗