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[Hyperbaric oxygenation (HBO) in the treatment of radiogenic side effects].

AIM: Many reports show that late complications of radiotherapy can be successfully treated by hyperbaric oxygen (HBO). This synopsis attempts to review the literature to identify areas of clinical use and further research. PATIENTS AND METHODS: Clinical and experimental data about HBO treatment of radiation late effects are analysed. Mechanisms of hyperbaric oxygen in the treatment of late radiation side effects are discussed. RESULTS: There is evidence in the literature that HBO is beneficial in the treatment of radiation cystitis, osteoradionecrosis of the mandible, hemorrhagic proctitis, soft tissue necrosis and neurologic deficits. The prophylactic use of HBO has shown to prevent the development of osteoradionecrosis after tooth removal and the loss of titanium implants in irradiated facial bones. The physiologic basis of HBO can be referred to induction of neoangiogenesis and revascularisation. CONCLUSIONS: Clinicians can be encouraged to use hyperbaric oxygen for the treatment of radiation cystitis, osteonecrosis of the mandible, hemorrhagic proctitis, soft tissue necrosis and neurologic deficits following radiation therapy.

Animals↗

[Perianal dermatitis].

The most often seen perianal dermatitis is the eczema, which is caused symptomatically by haemorrhoids, fissures, fistulas, proctitis, contact allergies, the funnel shaped anus and intensified folding of the perianal skin. Before treatment of the eczema all these causes have to be eliminated. Differential diagnosis of the perianal dermatitis are psoriasis, seborrheic dermatitis, endogenous eczema, intertrigo, proctitis and skin cancer.

Anus Diseases↗

Extensive ulcerative colitis and extraintestinal manifestations in a patient with HIV infection and significant CD4 T-cell lymphopenia.

We report a heterosexual patient with HIV infection and a CD4 T-cell count of 0.45 x 10(9)/L who developed mild ulcerative proctitis, sacroileitis and oligoarthiritis. While he was treated with 5-aminosalicylic enemas, the patient rapidly developed severe pancolitis. An emergency colectomy without procetectomy was performed. A few months later, he suffered recurrence of ulcerative proctitis, aggravation of arthritic pain and developed anterior uveitis. All symptoms disappeared after proctectomy. There was no evidence for opportunistic infection or Kaposi's sarcoma. Antineutrophil cytoplasmic antibodies were positive and the HLA-B27 antigen was present. CD4 counts were lower during the phases of active disease than during remission. This case demonstrates that severe ulcerative colitis can occur in the presence of moderate T-cell defects. In view of a recent report of remission of Crohn's disease under comparable circumstances, it is possible that the extent of T-cell involvement in both diseases is radically different.

Acquired Immunodeficiency Syndrome↗

Ultrasonic fragmentation. A new technique for mucosal proctectomy.

We report a new technique for mucosal proctectomy that does not require manual separation of the mucosa and submucosa from the underlying muscularis. Mucosal proctectomy using ultrasonic fragmentation of the rectal mucosa was performed in four patients. Three had severe ulcerative colitis, and one patient had radiation proctitis with a rectal stricture. In all cases an endorectal pullthrough with anastomosis to the area of the dentate line was performed. Healing after ultrasonic mucosal proctectomy occurred without infection or retraction. Ultrasonic fragmentation offers an alternative to the standard technique of mucosal proctectomy. This new method is useful in those patients in whom separation of the rectal mucosal layer is difficult to perform.

Adult↗

Piroxicam decreases postirradiation colonic neoplasia in the rat.

This study evaluated the effects of the nonsteroidal antiinflammatory agent piroxicam on chronic radiation proctitis in the rat. Forty female Wistar rats received a 2250-cGy dose of irradiation to the distal 2 cm of the colon. Twenty received piroxicam 8.0 mg/kg orally 30 minutes before exposure and 24 hours after exposure; 20 rats served as irradiated controls. All animals were evaluated by colonoscopy 1 and 3 weeks postexposure and every third week until death or killing at 1 year. At killing, colons were removed for light microscopic examination. One year postirradiation results showed no differences in mortality, vascular changes, acute inflammation, colitis cystica profunda, or rectal stricture between the control and piroxicam-treated groups. However, at 1 year postirradiation the control group demonstrated neoplasia in 15 of 19 animals compared with eight of 20 animals in the piroxicam-treated group. The first endoscopic appearance of colonic neoplasm occurred at 15 weeks postirradiation in one control irradiated rat whereas the first evidence of endoscopic neoplasm in the piroxicam-treated group did not occur until 36 weeks postirradiation. Histologic examination documented a tendency toward a greater presence of adenocarcinomas in the control group compared with the piroxicam-treated group. The authors conclude that piroxicam treatment significantly decreased the incidence of colonic neoplasia in general as well as delayed the endoscopic appearance of colonic neoplasia in rats after pelvic irradiation.

Adenocarcinoma↗

Drug therapy of inflammatory bowel disease.

Although the etiology of inflammatory bowel disease is unknown and specific therapy is unavailable, enough information on existing empiric agents is available to allow rational therapy. These agents include sulfasalazine, steroids, immunosuppressive drugs, metronidazole and cholestyramine. Sulfasalazine is a two-part molecule that depends on bacterial cleavage in the colon to deliver locally acting 5-aminosalicylate, whose mechanism of action may relate to inhibition of prostaglandin synthesis. The other half of the molecule, sulfapyridine, is responsible for most of the side effects of the drug. While the efficacy of sulfasalazine in the treatment and prevention of attacks of ulcerative colitis is well established, its use in Crohn's disease appears to be limited to patients with active colitis and ileo-colitis. Sulfasalazine is of major benefit in preventing relapses in patients with ulcerative colitis in remission. New formulations of 5-aminosalicylate may allow delivery of the apparently active moiety to the small bowel and colon without concomitant sulfapyridine toxicity. Corticosteroids are highly effective in acute attacks of ulcerative colitis and Crohn's ileitis and ileo-colitis; the mechanism of antiinflammatory action remains speculative. However, maintenance therapy with steroids is ineffective in preventing relapses or recurrent attacks of either ulcerative colitis or Crohn's disease. Steroid enemas allow topical administration to patients with distal colitis and proctitis with few systemic side effects. In children with growth failure associated with active Crohn's disease, amelioration by steroid therapy may actually restore normal growth. Immunosuppressive agents such as azathioprine and 6-mercaptopurine are of little value in active Crohn's disease when administered alone; however, in combination with other agents they may help diminish steroid dose, close fistulae and prevent relapse. Their mode of action likely depends on long-term cytostatic effects on immune effector cells. Concern for leukopenia and the development of late malignancy has limited their use to patients not responding to other therapies. Metronidazole, an antimicrobial agent that is effective against anaerobes, has recently been shown useful in Crohn's disease involving the colon and perianal area. Its mechanism of action is uncertain, but may be related to its antibacterial actions on anaerobes. Cholestyramine can be successfully used to control bile salt-induced diarrhea in Crohn's patients with terminal ileal resections. Effective drug therapy of inflammatory bowel disease is only part of a total program of management including reassurance, frequent explanation, well-timed use of surgery, and an understanding physician.

Adjuvants, Immunologic↗

The value of exfoliative cytology in the diagnosis of rectal malignancy.

This study has assessed the feasibility and reliability of cytology smears taken from patients with known rectal carcinomas without the use of any special instruments. In a pilot study of 23 patients who all had proved rectal cancer, 19 patients had satisfactory smears, one of which produced a false negative result. The remaining 18 displayed varying degrees of dysplasia (10) or frank malignancy (8). One of the patients with a smear containing severely dysplastic cells had a negative biopsy but had clear clinical and radiological evidence of a rectal tumour. Subsequently, a blind controlled study was undertaken on 29 patients with either carcinoma, proctitis or a normal rectum. All 29 sets of smears were of diagnostic quality and were correctly diagnosed as benign or malignant by the cytologist who had no knowledge of the clinical diagnosis. This is a rapid and simple diagnostic test which, if positive for malignancy, allows treatment to be planned at the first consultation. In combination with a forceps biopsy, the rate of positive diagnosis may be increased. A dysplastic smear adds to the level of clinical suspicion and confirms the need for biopsy of a lesion.

Adenocarcinoma↗

Carcinoembryonic antigen in patients suffering from ulcerative proctocolitis.

Carcinoembryonic antigen (CEA) has been measured by radioimmunoassay in samples obtained from all patients suffering from ulcerative proctocolitis and seen within a four-month period. The characteristics of this group of patients have been compared with reported epidemiological studies in this disease, and have been found to have a similar sex ratio and age of onset, but a more limited disease. Among 59 patients, 11 were found to have elevated circulating CEA values. One of the 11 had a colonic carcinoma and another was pregnant. Excluding these two patients, an overall prevalence of elevated CEA levels of 17.5% was found. The prevelance in ulcerative proctitis was 7.1%, and in colitis was 19.9%. The patients in whom elelvated plasma CEA values were found were compared with the remaining patients in relation to factors known to be associated with an increased propensity for the development of colorectal carcinoma complicating ulcerative colitis. There was no difference in mean age of the patients at disease onset, nor was there any difference in disease duration, extent, and control. A significant correlation was found between elevated plasma CEA levels and the severity of the initial attack. One patient with premalignant changes in the rectal mucosa had consistently normal concentrations of plasma CEA. There was no significant correlation between elevated plasma CEA values and disease activity. The mean age of the two groups of patients was similar. No carcinoma has manifested in any patient during follow-up periods of at least 18 months.

Adult↗

Serum lysozyme, serum proteins, and immunoglobulin determinations in nonspecific inflammatory bowel disease.

The serum levels of lysozyme, serum electrophoresis, and serum immunoglobulins were determined prospectively in 101 patients with ulcerative colitis, ulcerative proctitis, Crohn's disease, or nonclassifiable nonspecific inflammatory bowel disease. Although the mean serum lysozyme concentration of patients with Crohn's disease (10.5 +/- 6.8 microgram/ml) and ulcerative colitis (9.6 +/- 4.1 microgram/ml) performed by a standardized lysoplate method was significantly greater than normal controls (6.0 +/- 1.5 microgram/ml), the results did not correlate with the diagnosis nor with the degree of disease activity. Individually separated protein fractions and serum immunoglobulins also did not correlate with the serum lysozyme levels. This study indicates that measurement of the level of serum lysozyme in individual patients is not helpful in determining the cause or degree of activity of nonspecific inflammatory bowel disease.

Adult↗

Serial carcinoembryonic antigen (CEA) blood levels in patients with ulcerative colitis.

Fifty-seven patients with ulcerative colitis were folloued 1-49 months (mean, 18 months) with serial CEA determinations during periods of remission, mild relapses, and severe relapses. Elevated CEA titers correlated with activity and possibly extent of disease: 12% of patients with proctitis, 47% of patients with left-sided colitis, and 60% of patients with transverse or universal colitis had elevated CEA titers during a flare. Moreover, 24% of patients with mild flares and 86% of patients with severe flares had elevated CEA titers. Ninety-two percent of patients with extensive disease and severe flares had elevated CEA titers. Elevated CEA titers were correlated with histologic findings in three patients. Inflammation of mucosa was demonstrated by colonoscopy and confirmed by biopsy in one patient with persistently elevated CEA titers during clinical remission. In two other patients with active disease whose CEA titers fell prior to colectomy, marked denudation of colonic mucosa was noted. In this study, a transiently elevated CEA titer indicated either clinically active ulcerative colitis or active inflammation of colonic mucosa.

Carcinoembryonic Antigen↗

[The abdominoendorectal resection with peranal anastomosis in the treatment of radiation injuries of the rectum (author's transl)].

During the period 1974-1980 39 patients underwent operations at the Prosper Hospital in Recklinghausen for radiation injuries to the rectum or rectosigmoid. They comprised 22 patients with rectovaginal fistulas, 6 with ulcers, 3 suffering from severe hemorrhagic proctitis, 5 with rectal strictures, 1 with necrosis, and 2 with radiation ulcers and carcinoma. A sphincter-saving operative method of treating postirradiation damage of the rectum is presented. The technique involves the peranal anastomosis of healthy colon to the midanal canal using a sleeve anastomosis. Technical and functional results of resectional surgery for the rectal complications of radiation therapy are reported. Subjectively, total continence was present in 78%, only 1 patient was incontinent because of flatus and watery stools.

Adult↗

Results of coloanal anastomosis. A prospective study.

Anterior resection with colo-anal anastomosis was carried out in 40 patients. The main indications were rectal neoplasia (30 cases) and irradiation proctitis (8 cases). Early complications occurred in 12 patients and three died of cardiopulmonary complications. Fistula formation and stenosis were the most frequent late complications. In 23 patients with adenocarcinoma operated for cure there was one recurrence. The functional results were good, although it often took up to 1 year until satisfactory continence, stool consistency and frequency were obtained. Manometry showed a significant decrease in anal canal length and resting tone postoperatively. The method is a practicable alternative to total rectal excision.

Aged↗

Pitfalls of a 99mTc-RBC bleeding study due to gallbladder and ileal-loop visualization.

A series of 99mTc-labeled red blood cell (RBC) scintigrams in a patient with a past history of radiation proctitis demonstrated incidental findings of gallbladder activity, probably related to multiple blood transfusions and renal failure. Variable activity in an ileal-loop urinary diversion simulating bowel pooling was also noted. Thus, difficulties encountered in scan interpretation are presented.

Blood Transfusion↗

Cytokine production in pouchitis is similar to that in ulcerative colitis.

PURPOSE: Controversy exists as to whether pouchitis represents a reactivation of the immunologic mechanisms that lead to ulcerative colitis (UC). The aims of this study were to determine local levels of the cytokines: interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF alpha) in the mucosa of patients with "asymptomatic" ileoanal pouch (n = 25), pouchitis (n = 9), active UC (n = 20), normal ileum (n = 15), proctitis (n = 10), and normal colon (n = 15). METHODS: Lamina propria mononuclear cells were isolated from mucosal biopsies by enzymatic dispersion and cultured for 48 hours. Proinflammatory cytokine levels were measured in the supernatants by enzyme-linked immunosorbent assay. RESULTS: IL-1 beta, IL-6, IL-8, and TNF alpha secretions were significantly greater in pouchitis and active UC than in the noninflamed ileoanal pouch and normal controls (P < 0.001). There was significant correlation (r = 0.63, P < 0.05) between levels of cytokines expressed in pouchitis and active UC. CONCLUSIONS: Increased cytokine expression occurs in both active UC and pouchitis and to a lesser extent in the long-standing ileoanal pouch.

Adolescent↗

Preoperative hypoxyradiotherapy of colorectal carcinoma.

AIM: The article focuses on the radioprotective effect of acute hypoxia on healthy tissues during preoperative accelerated hypoxyradiotherapy of colorectal carcinoma performed as locoregional irradiation including the common iliac lymph nodes. Analysis of early and late side effects and complications. PATIENTS AND METHODS: In this prospective study, early and late complications were assessed in 50 patients as a function of hypoxyradiotherapeutic dose increase. The preliminary treatment results of this radiotherapeutic modification were evaluated after a median follow-up of 48 months using Kaplen-Meier analysis. Between April 1991 and February 1997, 50 patients (36 men and 14 women) with colorectal carcinoma were treated preoperatively with locoregional accelerated hypofractionated hypoxyradiotherapy. The extent of disease was classified according to Dukes' criteria (A: four patients, B. 28 patients, C: 18 patients). We used a 20-MeV linear accelerator with two parallel opposed fields. Hypoxyradiotherapy was performed extending from the perineum to the L4 region. Acute hypoxia was induced during irradiation by ventilation of a hypoxic gas mixture containing 7.8-8.0% oxygen. Total doses of 24 Gy/8 days, 28 Gy/9 days, and 32 Gy/10 days were applied in five, 20, and 25 patients, respectively. Low anterior resection or abdominoperineal amputation of the rectum was performed the day after completion of preoperative hypoxyradiotherapy. The early reactions after irradiation were evaluated according to the Common Toxicity Criteria of the National Cancer Institute (CTC-NCI). RESULTS: Early postirradiation proctitis was documented in three and early radiation-induced cystitis in two patients only. Neither early nor late radiation-associated complications were observed in any of the three hypoxyradiotherapy schedules during the follow-up period of 6-105 months. Based on Kaplan-Meier analysis (median 48 months), a 5-year overall survival rate of 61.5% and a local relapse-free survival rate of 84.2% can be expected. Treatment failures were predominantly systemic. CONCLUSION: We believe it can be concluded that acute hypoxia has a radioprotective effect on normal tissues during accelerated hypoxyradiotherapy of colorectal carcinoma. Hypoxyradiotherapy permits safe administration of doses higher than those tolerated by normoxic, noncanceorus tissue, resulting in the amplification of the biological effect of radiation on tumor tissue and contributing to an improved outcome after combined radiosurgical treatment of colorectal carcinoma.

Adult↗

[Curative radiotherapy of localized prostate cancer. Treatment methods and results].

Radiation oncology has undergone rapid technical development during the last few years. The further development of treatment planning systems and treatment machines had a major impact on the improvement of radiation therapy results in prostate cancer. This paper presents different treatment modalities and results. Currently available are three-dimensional conformal radiation, intensity modulated radiation therapy (IMRT), high dose rate brachytherapy, and low dose rate brachytherapy (seed implantation). All modalities offer the possibility for dose escalation, which is essential for curative treatment. Dose escalation using these techniques makes it possible to reduce the dose for the surrounding organs at risk. Three-dimensional conformal radiation therapy can be delivered with doses up to 78 Gy. The biochemical control rate is up to 90% depending on the risk factors T stage, initial PSA, and Gleason score. The incidence of late side effects is <10%. IMRT is a newer modality for percutaneous radiotherapy. By individual dose modification in the treatment fields, doses >80 Gy can be delivered in small treatment volumes. Treatment has to be highly precise to avoid dose peaks in the organs at risk, i.e., rectum and bladder. The preliminary data for remission and toxicity rates are promising, but it is too early for final conclusions. For cases with high-risk factors such as PSA >10 ng/ml, Gleason score >6, and stage T3, percutaneous radiation can be combined with neoadjuvant or adjuvant hormonal treatment. Randomized trials showed an improvement of the results in favor of combined treatment. HDR brachytherapy in combination with external radiation is a good option for dose escalation in patients with locally advanced tumors and/or other high-risk factors. The biochemical control rates are between 60 and 84%, late effects occur in less than 10%. Seed implantation (LDR brachytherapy) as sole treatment is indicated for prognostically favorable situations (PSA <10 ng/ml, Gleason score < or =6, and T1c or T2a tumors). The biochemical control rates are between 80 and 90%. Toxicity consists of urine retention and proctitis, occurring in 10-20% of the patients.

Brachytherapy↗

Physiologic changes of the anorectum after pelvic radiotherapy for the treatment of prostate and bladder cancer.

INTRODUCTION: The effect of pelvic radiotherapy on anorectal function is not clearly documented and is investigated in this prospective study. METHODS: Thirty-one males (median age, 70 years) with carcinoma of the prostate (n = 28) and bladder (n = 3) completed proctitis/incontinence symptom score questionnaires and anorectal physiology studies before and six weeks after pelvic radiotherapy. At six months after completion of radiotherapy, 25 of these patients were studied again. The results were expressed as medians and ranges and compared by the Mann-Whitney U test (2-tailed). RESULTS: Six weeks and six months after treatment, respectively, the proctitis symptom scores (0 (0-4) vs. 2 (0-7) (P < 0.001) vs. 2 (0-5) (P < 0.001)) and the incontinence symptom scores (0 (0-5) vs. 4 (0-11) (P < 0.001) vs. 3 (0-14) (P < 0.001)) increased. Urgency, frequency of defecation, anorectal pain, incontinence to liquid stool and to flatus, and alteration in lifestyle were significant symptoms after treatment. The following measurements decreased: anal canal resting pressure (83 (35-137) vs. 79 (26-152) (P = NS) vs. 71 (29-97) (P < 0.01) cm H2O), the squeeze increment (152 (51-135) vs. 162 (63-321) (P = NS) vs. 108 (45-296) (P < 0.042) cm H2O), and the maximum tolerated rectal volume (245 (115-450) vs. 194 (112-344) (P < 0.05) vs. 200 (109-350) (P < 0.138) ml). The rectal electrosensory threshold increased (20 (5.4-44) vs. 22 (9-50.5) (P < 0.134) vs. 31.5 (13.6-76) (P < 0.001) mA). CONCLUSIONS: Anorectal symptoms at six weeks after pelvic radiotherapy are related to reduced rectal capacity and compounded at six months by diminished internal and external sphincter function and rectal mucosal sensitivity.

Adenocarcinoma↗

The etiology of anorectal infections in homosexual men.

The infectious etiology of symptomatic anorectal disease was studied in 52 homosexual men who did not have gonococci on initial Gram stain of anorectal exudate. Herpes simplex virus (HSV) was isolated from the anal canal or rectum in 15 of the 52 (29 percent) men and characteristically caused severe anorectal pain and focal ulcerations visible on sigmoidoscopy. Despite negative initial Gram stains, seven men (14 percent) had anorectal gonococcal infection. Six (12 percent) had syphilis, including two with dark-field positive anal lesions. Four were infected with enteric pathogens, including Giardia lamblia, Entamoeba histolytica or Campylobacter fetus ssp. jejuni. Chlamydia trachomatis (LGV 2 strain) was isolated from one patient with severe granulomatous proctitis. One or more etiologic pathogens were identified in 28 (67 percent) of 42 men who had anorectal leukocytic exudate and in two of 10 who did not (p = 0.01). A review of the prominent features of different etiologic forms of anorectal infection in homosexuals is presented.

Adolescent↗