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Impact of dose and volume on rectal tolerance.

Based on the successful results achieved in survival and local control with radiotherapy of prostate cancer recent studies tried to establish some models to reliably predict late rectal toxicity. In fact, the rectum, due to its location, represents an organ at risk of acute and late toxicity with the onset of acute or chronic radiation proctitis. The concept of late consequential effect has gained ground. It implies that the late damage might be a direct consequence of the acute damage. Dose-escalation studies, conformal radiotherapy (3D-CRT) and intensity modulated radiotherapy (IMRT) led to the identification of parameters, based on dose-volume histograms (DVH), able to separate patients at low and high risk of toxicity. Precise predictive dosimetric factors play a major role in the definition of the onset of toxicity. The monitoring system of late toxicity used by the authors is presented.

Dose Fractionation, Radiation↗

Organ-preserving multimodality management of squamous cell carcinoma of anal canal.

AIM: To study the efficacy of an organ-preserving, sequential chemoradiation therapy for squamous cell carcinoma of the anal canal, and of salvage surgery in those in whom this treatment fails. METHODS: Forty biopsy-proven untreated patients (28 men) with squamous cell carcinoma of the anal canal received two cycles of chemotherapy using cisplatin and methotrexate, followed by 45 to 60 (median 50) Gy external beam radiotherapy. Salvage surgery was offered to those in whom this treatment failed. Overall survival, disease-free survival and colostomy-free survival were analyzed. RESULTS: Most patients (n=35; 87%) had T3 or T4 lesions and 5 (12.5%) had involvement of inguinal nodes. Thirty-one patients (77.5%) had complete response after chemoradiation. Only three patients (7.5%) developed chemotherapy-related grade 3 mucositis and myelosuppression. Radiotherapy-related toxicity included grade III cystitis in one patient and grade III proctitis in three patients. Three patients had post-treatment anal stenosis requiring repeated dilatation and two had chronic non-healing ulcers at the anal verge. Nine patients had failure of chemoradiation or disease recurrence; of these, only 5 could undergo salvage surgery. After a median follow up of 60 months, overall survival, disease-free survival and colostomy-free survival were 80%, 77.5% and 72.5%, respectively. CONCLUSION: Chemoradiation is effective in the treatment of squamous cell anal cancer and has acceptable toxicity. Surgical salvage may be useful in those with failure of this treatment.

Adult↗

[An outbreak of lymphogranuloma venereum in Western Europe].

Lymphogranuloma venereum (LGV) is a sexually transmitted infection caused by Chlamydia trachomatis serotypes L1, L2, and L3. It is endemic in tropical areas, while seldom in industrialised countries. Since 2002, an outbreak of rectal LGV has been observed among men having sex with men, in Netherlands, France, and other countries of Western Europe. After an incubation period of 2 days to 2 months, LGV develops in three stages: ulcerated papule; inflammatory satellite lymph node and/or proctitis; chronic inflammatory complications (fistulas and sclerosis). Chlamydia trachomatis infection is confirmed by PCR and serovars is identified by RFLP of omp1 gene amplified by PCR. Recommended first line treatment is doxycycline for at least 21 days.

Adult↗

Efficacy and tolerability of olsalazine (dipentum) in the treatment of patients with ulcerative colitis--results of a field study.

BACKGROUND/AIMS: In the treatment of ulcerative colitis, 5-aminosalicylic acid is the standard therapy for both acute exacerbations of the disease and the maintenance of remission. Clinical studies have shown that olsalazine (Dipentum)--a prodrug converted to two molecules of 5-ASA by colonic bacteria-induces and maintains remission. This study aimed to investigate the efficacy and tolerability of olsalazine in patients with ulcerative colitis who were being treated in daily practice by private physicians specializing in gastroenterology. METHODOLOGY: A total of 260 patients with ulcerative colitis (aged 17-77 years, 116 men) were studied. The doses of olsalazine and the clinical data (including acute disease symptoms and the occurrence of adverse events) were recorded over a 6-month period. RESULTS: Twenty per cent of patients had pancolitis, 48% had left-sided disease and 32% had proctitis or proctosigmoiditis. At study entry, 86% of patients had active disease; the percentages of these patients in remission after 6 weeks and 6 months were 42% and 91%, respectively. Patients with active disease received a mean dose of olsalazine - 2324mg per day initially and 1325mg per day at 6 months. The corresponding figures for patients in remission at study entry were 1386mg and 1162mg per day, respectively. Seventy-three per cent of patients took olsalazine with food, as recommended. The overall rate of adverse events was low; no serious adverse events occurred. CONCLUSIONS: Olsalazine therapy resulted in a rapid regression in the acute symptoms of ulcerative colitis. Olsalazine was also effective in maintaining remission. The drug was well tolerated.

Adult↗

NOD2/CARD15 and Toll-like 4 receptor gene polymorphism in Chilean patients with inflammatory bowel disease.

Crohn's disease (CD) and ulcerative colitis (UC) are multifactorial diseases with a genetic background. Genes related to the innate immune response have been observed to be involved. Polymorphisms of Toll-like receptor 4 (TLR4) and CARD15/NOD2 are thought to be involved in the pathogenesis of inflammatory bowel disease (IBD). There is no information about the frequency of these polymorphisms in South American and Chilean populations. Aim. To investigate the distribution of CARD15/NOD2 (Arg702Trp, Gly908Arg and Leu1007fsinsC) and TLR4 (Asp299Gly) polymorphisms in Chilean patients with IBD. Methods. DNA was obtained from 22 CD, 22 UC patients and 20 healthy individuals. Genotyping was performed by allele-specific PCR and by PCR-RFLP analysis. Clinical and demographic features were characterized. Results. Among the CD patients, the clinical pattern was deemed inflammatory in 14, while five had penetrating and five stricturing, variants. One patient had esophageal involvement, five perianal, seven ileal and in 16 the colon was involved. Among the UC patients, two had proctitis, two proctosigmoiditis, four left-sided colitis and 14 pancolitis. NOD2/CARD15 analysis revealed the presence of the 702Trp allele in two CD patients (both heterozygotes), 1007fsinsC in one CD patient (heterozygote) while 908Arg was found in one UC patient. The 299Gly TLR4 allele was identified in one UC and one CD patient. Conclusion. This genetic study shows that the alleles frequently associated with IBD (1007fsinsC, 908Arg and 702Trp in NOD2/CARD15 and 299Gly TLR4) have a low incidence in Chilean, IBD patients, which is similar to European populations. It is possible that, in addition to environmental factors, other genetic polymorphisms may be involved in the pathogenesis of the disease in Chilean, IBD patients.

Chile↗

Lymphogranuloma venereum emerging in men who have sex with men in Germany.

A resurgence of lymphogranuloma venereum (LGV) has been observed in several European countries. LGV is not a mandatorily notifiable disease in Germany. Reports of LGV cases have actively been collected by the Robert Koch-Institut since 2004 to describe the outbreak and estimate the extent of the LGV problem in Germany. Updates on the LGV outbreak were published in the German national epidemiological bulletin. Physicians were asked to send their samples to a laboratory for genotyping. A possible case was defined as a person with symptoms of proctitis and/or inguinal lymph node swelling and a positive chlamydia serology. A probable case had in addition a positive chlamydia rectal or urinary PCR test. A case was confirmed if the genotype L1-L3 was identified based on sequence analysis of omp1 gene sequences. Since 2003, LGV has been reported in 78 male patients in Germany. Of these, 61 patients were confirmed as genotype L2. Fifty eight out of 78 patients (74%) are known to be men who have sex with men (MSM). Fifty five patients (71%) had rectal symptoms and 49 (63%) knew they were HIV positive. Sixty two (79%) of the patients were residents of Berlin or Hamburg. LGV has emerged in MSM in Germany at the same time as in other European countries. It is thought that LGV may become endemic in the MSM community in German metropolitan areas, because the number of reported patients with LGV continues to increase. The increase in the number of LGV cases and the high HIV prevalence in LGV patients are of great public health concern. Clinicians and MSM may not be sufficiently aware of the disease, and existing efforts to promote awareness and prevention of sexually transmitted infections and HIV need to be strengthened.

Disease Outbreaks↗

[Endometrial carcinoma treated by radiotherapy alone].

90 patients with endometrial carcinoma treated from 1958 to 1984 by radiotherapy alone are presented. They constituted 18.7% of all cases of endometrial carcinoma treated in the same period. According to the clinical staging system of FIGO, there were 28.89% Stage Ia, 8.89% Stage Ib, 38.89% Stage II, 20% Stage III and 3.33% Stage IV lesions. In this series, 82 patients suffered from adenocarcinoma and 8 patients from adenoacanthoma. Two treatment regimens were adopted: 1. intracavitary Ra (137Cs or 60Co) as the major form of treatment supplemented by external irradiation in 82 patients (including 5 by intracavitary 137Cs afterloading), 2. external irradiation supplemented by intracavitary Ra (or 137Cs) radiation in 8 patients. The overall 5-year survival rate was 48.89% (Stage I 58.82%, Stage II 51.42%, Stage III 33.3% and Stage IV 0%). Complications were proctitis in 17 cases hematuria in 4 and rectovaginal fistula in 1. The 5 patients treated by intracavitary afterloading radiation with high doses at reference points A and F all survived for more than 5 years. This may imply a bright future for this form of radiotherapy in the treatment of endometrial carcinoma.

Adenocarcinoma↗

Proctologic diseases in geriatric persons.

The aim of present study was the estimation of the frequency and kind of disease of the lower part of the digestive tract in aged patients, based on rectoscopic examination. There were undertaken rectoscopy and examination per rectum of 193 patients over 65 years (mean age 70.4 years from whom only 13 patients had not suffered from any sensations on the part of digestive tract and among 239 patients ranging up to 65 (mean age value 39.6 years from whom majority suffered from various sensations on part of digestive tract and were treated in Clinic of Gastrology and Angiology or Clinic Endoscopy Department. It was stated that the most frequent disease in the elder group of patients were: proctitis (or sigmoiditis) with accompanying spastic conditions of large bowel 14 per cent and hemorrhoids 46.4 per cent. Rectal polyps and sigmoidic polyps occurred in 8.1 per cent of the whole examined group, in the elder group they ranged to 10.4 per cent and in the younger one they ranged to 6.6 per cent. Cancers in rectum and sigmoid were present in 4.1 per cent of the whole examined group, in the elder group in 5.6 per cent and 2 per cent in the younger one.

Adult↗

[The therapeutic results and early and late toxicities of the treatment of anal canal carcinoma by radiotherapy or chemoradiotherapy].

From 1975 to 1989 114 patients with anal canal carcinoma were treated, 81 of these with radiotherapy (RT) alone and 33 with chemoradiotherapy (CRT), 80% respectively 82% of the patients were colostomy-free at the onset of therapy. RT was given to a total dose of 60 Gy in six weeks, for CRT additional simultaneous 5-fluorouracil (500 mg/m2 days 1 to 5 and 8 to 12) and mitomycin C (5 mg/m2 days 5 and 12) was administered. 67% respectively 82% of the patients had UICC stage II to IIIB disease predominantly with G2 and G3 squamous cell carcinomas. Local control after three years was 79% for the RT group vs. 82% for the CRT group. Three-year survival rate was 68% and 71%, respectively. These differences were not significant. Only for G1- compared to G3-tumors there is a significantly higher survival rate. Acute and late damage was slightly lower for the RT treatment group (77% and 25%) compared to the CRT group (79% and 30%). In both treatment groups there was one patient needing a permanent colostomy due to radiation induced proctitis. In conclusion, RT or CRT should be the primary form of treatment in patients with and canal carcinoma and abdominoperineal resection should only be performed in case of local recurrence or tumor persistence. The final decision about the indications for RT or CRT can only be made with the results of a prospective randomized trial.

Aged↗

Transperineal ultrasound-guided implantation of the prostate: morbidity and complications.

Two hundred and seventy four patients with early carcinoma of the prostate were treated by ultrasound-guided transperineal I-125 implantation. One hundred and ninety six received implant alone, and 78 were treated with combined external beam and I-125 implantation. Operative, early and late complications were reviewed with a median follow-up time of 40 months (minimum 13, maximum 64 months). Operative complications were negligible. Early morbidity (less than 12 months post implant) was noted in 10-15% of patients and consisted of self-limited irritative uropathy or obstruction. Late complications (more than 12 months post implant) were noted in 13%. Seven percent of patients had some combination of permanent sequelae of treatment: 14 patients had some degree of incontinence, 17 had irritative uropathy symptoms, and 7 had proctitis, 5 of whom resolved spontaneously. Most complications were mild to moderate with a notable absence of severe problems. Urinary morbidity was strongly related to prior or post-implant transurethral resection of the prostate (TURP) (24% with TURP, 3% without). Transperineal implantation in our experience is associated with an acceptable acute and chronic complication rate.

Brachytherapy↗

[The clinic diagnostic value of the rigid sigmoidoscopy].

Rigid sigmoidoscopy is beneficial as it detects rectal or distal sigmoidal lesions very efficiently and precisely. But it also has some complications, e. g. rectal injury, rectal perforation or transient bacteremia. In this prospective study, 800 cases were collected and divided into two groups. In group I, 400 O.P.D. symptomatic cases were chosen randomly and in group II 400 cases registered for routine physical examination were picked up. The positive detection rate was 7% in group I versus 2% in group II. The lesions detected in group I are 15 cases of cancer, 7 cases of polyp, 4 cases of irradiation proctitis, 2 cases of ulcerative colitis and 1 case of pseudomembranous colitis. Only 8 polyps are found in group II. The routine sigmoidoscopy is mandatory for symptomatic patients but it is not cost-effective for routine check-ups. The stool occult blood is the best screening test for detecting colorectal lesions. For routine physical examination, stool occult blood test is safe and easy to perform. If the stool occult blood test is positive, then further examinations will be necessary.

Adolescent↗

Inflammatory bowel disease. An epidemiological and genetic study.

The epidemiology of ulcerative colitis (UC) in Stockholm County over a 25-year period, 1955-1979, was investigated. There were 1,274 cases--681 males and 593 females. The proportion of patients with proctitis, left-sided, and total extent of disease remained constant over the study period, as did the time interval between onset of symptoms and definite diagnosis. The incidence increased over the first 20 years followed by a plateau and was 4.3 per 10(5) inhabitants at the end of the study period. The peak incidence in relation to age increased, but remained in the 3rd and 4th decade throughout the study period. In a population-based study of UC the overall prevalence of extracolonic diagnoses was 21%. Seventy percent of patients with extracolonic diagnoses had extensive colitis whereas among the patients without extracolonic diagnoses only 28% had extensive colitis (p less than 0.001). The extracolonic diagnoses were classified into two major groups, activity-related and autoimmune, the former is related to the extent and activity of UC and responds to both medical and surgical treatment, whereas the latter is unaffected by medical and surgical treatment for UC. A total of 364 diagnoses were distributed among 271 UC patients. The prevalence of extracolonic diagnoses was higher in familial UC (p less than 0.05), but was distributed as UC in general mostly with activity-related diagnoses. The familial occurrence of inflammatory bowel disease (IBD) was investigated among 963 patients with UC. There was a general prevalence of 7.9% for familial IBD. In 80% one relative was affected, in most cases this was a first degree relative with UC. Sibship was the most common relationship. No concordance for UC was found among three pairs of monozygotic twins. The prevalence of UC in first degree relatives of index patients was 15 times higher than in non-relatives. The age at onset was significantly lower among patients with a family history for UC; they also had a higher prevalence of total colitis. The prevalence of Crohn's disease (CD) in first degree relatives of index patients with UC was almost 3.5 times higher than in non-relatives. Complex segregation analysis of 124 families with UC where two or more individuals were affected points to a rare additive major gene with a low penetrance as the cause of the disease with. About 20% of the affected were heterozygotes for the gene. There was no evidence for multifactorial inheritance. The prevalence of IBD was found to be 13.4% in a population-based study on patients with CD.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

[Radiation enteritis: the results of surgical treatment].

We reviewed the results of surgical therapy for radiation enteropathy in 18 consecutive patients. Fifteen (83%) were females and the age ranged from 31 to 81 years old. The indication for radiotherapy was cancer of the cervix in 10 patients (56). The mean radiation dose was 5190 rads (range 4000 to 7000). Of 23 radiation lesions, 12 (52%) were located in the ileon, 10 in the rectum and 1 in the sigmoid. Fibrosis and stenosis was the most frequent lesion (70%) followed by fistulae (22%) and proctitis in 2 patients. Resection or derivation was the surgical treatment employed in 22 of the 23 lesions. For lesions of the ileon, we performed resection and anastomosis in 7 patients and derivation in 5. For rectal lesions we performed resection, endoanal descent and colo-anal anastomosis in 7 patients anterior resection in 2 and colostomy in 1. Complications were observed in 5 patients (28%) and 1 patient died (5%). After a mean follow up of 56 months, 5 patients have died from recurrence of the original neoplastic lesions. We feel that surgical treatment allows improvement in quality of life of patients with radiation enteropathy.

Adult↗

[Incidence of inflammatory bowel disease in the Nord-Pas-de-Calais region and the Somme area of France in 1988].

No epidemiological data on inflammatory bowel disease (IBD) are available in France. We therefore conducted a prospective epidemiologic study of IBD in the Nord-Pas de Calais region and the Somme department of France (4.5 million inhabitants). Each suspected new case was reported by all (private and public) gastroenterologists (n = 120) and a questionnaire was filled out at the gastroenterologist office by an epidemiologist. The final diagnosis of Crohn's disease (CD), ulcerative colitis (UC), or proctitis (UP) was made in a blind manner by two gastroenterologists. During 1988, 576 IBD patients were identified; 281 (49 percent) had CD, 207 (36 percent) had UC including 75 UP; and 88 (15 percent) had unclassified colitis. The incidence rate per 10(5) was 6.3 for CD and 4.6 for UC. The female/male ratio was 1.4 for CD and 0.9 for UC. The mean age at the time of diagnosis was 31 years for CD and 40.5 years for UC. The mean time between onset of symptoms and diagnosis was longer for CD (15 months) than for UC (6.8 months). These preliminary data suggest that the incidence of IBD is high in Northwestern France and comparable, for CD, to the highest incidence of Northern Europe.

Adolescent↗

Incidence of Chlamydia trachomatis infection related to selected signs and symptoms of lower genital tract infections in women.

Chlamydia trachomatis infections of the female reproductive tract is associated with a spectrum of clinical syndromes from simple colonization to mucopurulent cervicitis, urethritis, proctitis, and pelvic inflammatory disease. Its natural history and tendency for progression is unclear. It is said these infections are the most common of all sexually transmitted diseases.

Chlamydia Infections↗

Photon-neutron therapy for recurrent colorectal cancer--follow up and preliminary results.

26 patients with unresectable locally recurrent adenocarcinoma of the rectum were treated with a mixed beam schedule. 40 Gy photons were delivered to the whole pelvis followed by a neutron boost of 6.6 or 10 Gy. Neutron therapy was carried out with a 14 MeV d-t generator (KARIN) using an isocentric are technique. Fluctuation in neutron dose rate during irradiation was monitored by a computer which controlled the gantry speed. All patients were followed clinically by CEA monitoring and CT-scans. In 18 patients positron-emission-tomography (PET) was used to verify the therapeutic efficacy. All patients were symptomatic with severe pain prior to therapy. After a mean follow-up interval of 12.8 months (range six to 26 months), the palliative effect in terms of pain relief was excellent in 22 patients in spite of the poor general condition of most patients and the large tumor extension. In four patients, further pain symptoms developed again after six to nine months due to renewed tumor progression. We observed proctitis at late side effects in one, enteritis in two and a fistula in one patient six to ten months after therapy. Changes in tumor glucose metabolism were monitored by serial PET examinations in all patients. The typical pattern observed by PET was a decrease in the F-18-Deoxyglucose (FDG) accumulation, approximately six weeks after onset of therapy.

Adenocarcinoma↗

Allergy-related proctocolitis in infants: diagnostic usefulness of rectal biopsy.

To evaluate the diagnostic utility of rectal mucosal biopsies in infants with proctocolitis, we compared the clinical and histologic features of an allergy-related group (N = 36) with those of normal (N = 12) and inflammatory (N = 8) controls. Clinical features were nondiscriminatory among the three groups of patients, except for an increased absolute peripheral eosinophil count in the allergic group. Similarly, morphologic evidence of proctitis (cryptitis and crypt abscesses) and small or moderate numbers of eosinophils (less than or equal to 60 per ten high power fields) in the lamina propria of the biopsies did not discriminate among the three groups. However, large numbers of eosinophils (greater than 60 per ten high power fields) and eosinophils located in the muscularis mucosae or as the predominant cell in crypt abscesses were significantly associated with allergy-related disease. No histologic features of chronic colitis were noted in the allergy-related group. Thus, in tandem with the remainder of the clinical data, rectal mucosal biopsy is a useful adjunct in the diagnosis of allergic proctocolitis.

Biopsy↗

Colostomy as treatment for complications of spinal cord injury.

We reviewed our experience with colostomy performed in 20 spinal cord injury (SCI) patients to determine the effectiveness and safety of colostomy when it is performed for a late complication of SCI. Objective evaluation of gastrointestinal function, ie, colonic transit time and anorectal manometry, was performed in six patients with chronic gastrointestinal complaints to identify the site and severity of bowel dysfunction. Twelve patients had colostomy performed for chronic gastrointestinal problems, seven as an adjunct in the treatment of perineal pressure ulcers, and one for rectal cancer. When patients with difficult bowel evacuation or incontinence were considered, colostomy reliably simplified bowel care, relieved abdominal distention, and prevented fecal incontinence. The amount of time spent on bowel care decreased from an average of 98.6 min/day to 17.8 min/day (p less than .05) after colostomy. When performed as an adjunct in the treatment of pressure ulcers, colostomy provided a dry, clean environment, and seven of seven ulcers healed. Colostomy was well accepted by all patients; all patients with chronic gastrointestinal complaints reported that colostomy improved the quality of their lives. Objective testing differentiated between failure of the colon to adequately transport material to the rectum and inability to adequately evacuate the rectum. Testing was useful in choosing the level at which a colostomy was created, and, in one instance, it identified a specific syndrome (ischemic proctitis) which required colostomy.

Colostomy↗