Effect of interval between preoperative radiotherapy and surgery on clinical outcome and radiation proctitis in rectal cancer from FOWARC trial.

OBJECTIVE: The aim of this study was to evaluate the effect of the interval between CRT and surgery on radiation proctitis, the pathologic response, and postoperative morbidity. METHODS: This was a cohort study from a phase III, randomized controlled trial (FOWARC study, NCT01211210). Data were retrieved from the leading center of the trial. Patients were divided into the short-interval (≤7 weeks) group and the long-interval (>7 weeks) group. The rate of radiation proctitis, pathologic complete regression (pCR) and morbidities were calculated for each group. Multivariate analysis was used to verify the impact of interval on radiation proctitis. RESULTS: Surgery was performed in 60 patients after an interval of ≤7 weeks and in 97 patients after an interval of >7 weeks. The two groups according to interval were comparable in terms of baseline demographic and clinicotherapeutic characteristics. Radiation proctitis was identified by imaging in 9 (15.0%) patients in short-interval group and in 31 (32.0%) patients in long-interval group (P = .018). Multivariate analysis confirmed the correlation between long interval and radiation proctitis (P = .018). The long interval was significantly associated with longer median operation time compared to the short interval (P = .022). The rates of pCR and postoperative complications were not different between two groups. CONCLUSIONS: A longer interval after CRT may be associated with higher rate of radiation proctitis and longer operation time. Moreover it did not increase the rate of pCR.

Clinical diagnostic and therapeutic aspects of 221 consecutive anorectal Chlamydia trachomatis and Neisseria gonorrhoeae sexually transmitted infections among men who have sex with men.

OBJECTIVES: Proctitis caused by Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are known as sexually transmitted infections (STI). This study describes their clinical, diagnostic and therapeutic aspects. METHODS: Between 01/2013-03/2015, all MSM consulting for proctitis at proctology Institute-Saint-Joseph's Hospital, Paris, were included. Demographic, past-medical history, STI status and medical treatment were collected. Detection of CT/NG was performed by Transcription-Mediated Amplification (TMA) and antimicrobial susceptibilities for Ng by agar diffusion method. RESULTS: On 441 rectal samples collected, 221 (50.1%) were positive: 109 Ct (49.3%), 70 Ng (31.7%), 42 positive for both etiologies (19%). Among Ng infections, no resistance was detected to azithromycin and ceftriaxone. However, 84 strains (43.2%) were resistant to fluoroquinolones. More than one episode was diagnosed for 10 (5.1%) and 12 (6.2%) patients with CT and NG infections respectively. Anal abscesses were found for 27 (13.9%) patients, and 14 (7.2%) of them underwent surgery for anal fistula. CONCLUSIONS: The prevalence of CT/NG anorectal infections described is high on symptomatic patients, and a significant level of abscess was reported. These results confirm the interest of the association of recommended antibiotics excluding quinolones. Prospective studies would be relevant on complicated forms of anorectal infections.

Clinical Characteristics of Anorectal Mycoplasma genitalium Infection and Microbial Cure in Men Who Have Sex With Men.

BACKGROUND: We report clinical characteristics of proctitis caused solely by Mycoplasma genitalium (MG) compared with chlamydia and gonococcus. We determined the proportions cured with first-line (azithromycin) and second-line antimicrobials (moxifloxacin, pristinamycin). METHODS: A total of 166 patients attending Melbourne Sexual Health Centre from 2012 to 2016 with symptoms of proctitis were tested for MG, Chlamydia trachomatis, and Neisseria gonorrhoeae. Demographic characteristics, sexual behaviors, clinical symptoms, and signs were recorded. Multinomial multivariable logistic regression was used to test for significant differences in symptoms and signs for the pathogens detected. RESULTS: Seventeen percent of men had MG (95% confidence interval, 12-24), 21% had chlamydia (15-27), and 40% had gonococcal monoinfection (32-48), whereas 22% had MG coinfection (16-29). Relative to men with MG monoinfection, those with chlamydial monoinfection reported more anal pain (adjusted prevalence odds ratio (aPOR), 4.68 [1.41-14.19]), whereas men with gonococcal monoinfection reported more anal pain (aPOR, 6.75 [2.21-20.55]) and tenesmus (aPOR, 15.44 [1.62-146.90]), but less anal itch (aPOR, 0.32 [0.11-0.93]). The microbiological cure for MG using azithromycin was low at 35% (22-50), whereas moxifloxacin subsequently cured 92% (64-100) and pristinamycin cured 79% (54-94) of infections. CONCLUSIONS: M. genitalium was almost as common as chlamydia in men presenting to a sexual health center with symptoms of proctitis. Men with anorectal MG monoinfection were less likely to have symptoms and signs compared with those with chlamydia or gonococcus monoinfection. Cure for men with symptomatic anorectal MG by azithromycin was low. We suggest routine testing for MG in cases of proctitis, with test of cure after treatment being essential.

Feasibility study of toxicity outcomes using GEC-ESTRO contouring guidelines on CT based instead of MRI-based planning in locally advanced cervical cancer patients.

PURPOSE: To report late rectal and bladder toxicity outcomes of a CT-based image-guided brachytherapy (IGBT) technique for treatment of cervical cancer. METHODS AND MATERIALS: Between 2008 and 2014, 95 women with International Federation of Gynecology and Obstetrics stage IB to IVA cervical carcinoma treated with definitive concurrent cisplatin-based chemotherapy and external beam radiation therapy 50.4 Gy in 28 fractions followed by planned prescription dose of 7 Gy × 4 fractions of high-dose-rate IGBT was retrospectively reviewed. At each implantation, all patients had a urinary catheter in situ and received bowel enema before undergoing planning CT simulation. A high-risk clinical target volume (HRCTV) as per GEC-ESTRO guidelines and the entire cervix, rectum, and bladder was contoured on the simulation CT according to Radiation Therapy Oncology Group Gynaecology Contouring Atlas. Reported doses to HRCTV and organs at risk were recorded. Toxicities were recorded using National Cancer Institute Common Terminology Criteria for Adverse Events version 3. RESULTS: The median followup time was 29 months. The mean HRCTV equivalent dose in 2 Gy fractions (EQD2) of external beam radiation therapy combined with brachytherapy was 80 Gy (standard deviation [SD], 11), and the rectal doses to 2 cm3 (D2cc) EQD2 and bladder D2cc EQD2 were 74 Gy (SD, 6) and 79 Gy (SD, 15), respectively. Twenty-two patients (23%) had grade 2 proctitis and 10 patients (11%) had grade 3 proctitis. Four patients (4%) had grade 2 cystitis and two patients (2%) had grade 3 cystitis. No patients had ≥ grade 4 toxicity. CONCLUSIONS: Despite CT-based brachytherapy planning, reported organ at risk toxicity was still significant compared with reported MRI-based planning series. Coimplementation of interstitial IGBT using the European Study on MRI-guided Brachytherapy in Locally Advanced Cervical Cancer (EMBRACE) protocol or using intensity-modulated radiation therapy during the external beam phase treatment might help to limit these late toxicities.

Hyperbaric oxygen therapy for chronic radiation-induced tissue injuries: Australasia's largest study.

AIM: Chronic radiation injuries, although uncommon, are associated with poor quality of life in oncology patients. The present study assesses the efficacy and safety of hyperbaric oxygen therapy in the management of chronic radiation-induced tissue injuries. METHODS: A retrospective analysis was performed in 276 consecutive patients treated with hyperbaric oxygen therapy for chronic radiation-induced tissue injuries at the Hyperbaric Medicine Unit, Townsville, Queensland, between March 1995 and March 2008. Of these patients, 189 (68%) had complete follow-up data and were assessed. RESULTS: A total of 265 events of chronic radiation tissue injury were experienced by the 189 patients treated with hyperbaric oxygen therapy. Osteoradionecrosis prophylaxis due to radiation-induced dental disease had an overall response rate of 96% (P=0.00003; Wilcoxon matched-pairs signed-rank test). The overall response rates for established osteoradionecrosis of mandible, soft tissue necrosis of head and neck, and xerostomia were 86% (P=0.00001), 85% (P=0.002) and 64% (P=0.0001), respectively. The overall response rates for soft tissue necrosis at other sites, chronic radiation proctitis and hemorrhagic cystitis were 84% (P=0.03), 95% (P=0.0001) and 85% (P=0.03), respectively. The total complication rate after hyperbaric oxygen therapy was 15.9%, comprising reversible ear barotrauma (10.6%), reversible ocular barotrauma (4.2%), dental complications (0.5%) and myocardial infarction (0.5%). CONCLUSION: Our study demonstrates that hyperbaric oxygen therapy can be effectively used in a variety of chronic radiation-induced tissue injuries; its favorable risk profile suggests it should be considered for patients with radiation-induced tissue injuries.

Hemorrhoid management in patients with radiation proctitis.

PURPOSE: Management of rectal bleeding in patients with radiation proctitis presents a conundrum for practitioners. Surgeons are appropriately concerned about using conventional methods of treatment in these patients, such as cautery for bleeding areas in the rectum, rubber band ligation, or excision of internal and/or external hemorrhoids, for fear of poor healing and possible exacerbation of the original problem. Few randomized controlled trials are available on the treatment of radiation proctitis alone, and no literature exists pertaining to the management of symptomatic hemorrhoids in the radiated patient. METHODS: In the absence of observational studies, the authors created an email survey to distribute to the membership of the American Society of Colon and Rectal Surgeons in order to try to identify current management practices for radiation proctitis and for the treatment of their symptomatic hemorrhoids. RESULTS: Of the 327 respondents, 85 % favored the use of topical formalin to treat radiation proctitis, while 42 % additionally used argon plasma coagulation. Only 25 % of practitioners report using sucralfate, though existing data on this therapy are promising. Regarding the management of hemorrhoids in patients with a history of rectal irradiation, 55 % of respondents hoped treatment of radiation proctitis alone would solve the problem. Forty-three percent reported using rubber band ligation, 30 % using hemorrhoidectomy, and 18 % using sclerotherapy. CONCLUSIONS: While most respondents treated radiation proctitis alone in patients with symptomatic hemorrhoids, many also felt rubber band ligation, hemorrhoidectomy, and sclerotherapy are safe and effective alternative therapies in this population.

The use of hyperbaric oxygen for treating delayed radiation injuries in gynecologic malignancies: a review of literature and report of radiation injury incidence.

PURPOSE: The purposes of this paper are to review the best evidence supporting the use of hyperbaric oxygen therapy (HBOT) in delayed radiation injuries in gynecologic malignancies and report the incidence of radiation injuries at two large medical centers in southeastern Wisconsin. METHODS: A literature search was performed on Google Scholar, PubMed, and Ovid for studies evaluating the use of HBOT radiation cystitis, proctitis, and necrosis. The studies were then reviewed for the highest quality evidence using American Academy of Neurology guidelines. To evaluate radiation injuries, cancer databases at Froedtert Memorial Lutheran Hospital (FMLH) and Aurora St. Luke's Hospital (ASLH) were accessed. RESULTS: Several studies support the use of HBOT in treating radiation cystitis, proctitis, and necrosis, with proctitis having the strongest evidence in its favor. The average annual incidence of radiation injury at FMLH was 13.8%. Patients with cervical cancer and vulvar cancer had rates of 23% each. The average annual incidence of radiation injury among gynecologic cancer patients at ASLH was 5.5%. CONCLUSIONS: There is level A evidence for using HBOT to treat radiation proctitis. There is level B evidence for using HBOT to treat radiation cystitis and necrosis. The incidence delayed radiation injuries can be as high as 23%. This has relevance in practice guidelines for the treatment of delayed radiation injuries in gynecologic malignancies.

Lymphogranuloma venereum proctitis in men who have sex with men is associated with anal enema use and high-risk behavior.

OBJECTIVES: In the industrialized world, lymphogranuloma venereum proctitis (LGVP) has been reported only in men who have sex with men. Factors responsible for the outbreak remain to be elucidated. GOAL: The goal of the present work was to elucidate risk factors associated with LGVP. STUDY DESIGN: The study design comprised a cross-sectional study including 32 men with LGVP and 93 men without LGVP (22 with gonorrheal proctitis, 30 with a non-LGV chlamydial proctitis, and 41 with proctitis of unknown etiology). Factors associated with LGVP were analyzed by (multinomial) logistic regression. RESULTS: Comparing men with LGVP with men without LGVP, factors significantly associated with higher risk of LGVP in multivariate analyses were as follows: anal enema use [odds ratio (OR): 7.8, 95% confidence interval (CI): 2.6-23.2], having sex on sex parties (OR: 5.7, 95% CI: 1.5-21.8), and having sex with human immunodeficiency virus-positive partners (OR: 3.2, 95% CI: 1.1-9.3). Evaluating the 4 proctitis groups separately in a multinomial logistic regression model, similar associations between anal enema use and LGVP were found. Men with non-LGV chlamydial proctitis showed less risk behavior than men with LGVP. No substantial difference in risk behavior was found, except for attending sex parties, between men with LGVP, and gonorrheal proctitis or proctitis of unknown etiology. CONCLUSIONS: Apart from men with LGVP, men with gonorrheal proctitis or proctitis of unknown etiology exhibit high risk behavior. Enema use seems to play a key role in transmission of LGVP, and needs further investigation.

Allergic proctitis and abdominal distention mimicking Hirschsprung's disease in infants.

AIM: To determine the incidence and clinical aspects of allergic proctitis (AP) in infants with symptoms that mimic Hirschsprung's disease (HD). METHODS: One hundred and five patients less than 6 months of age, who underwent barium enema, anorectal manometry and rectal suction biopsy due to suspicion of HD, were enrolled. Comparison of the patient characteristics associated with each disease was based on the results of the triple testing. The sensitivity and specificity of the three tests, for the diagnosis of HD, were evaluated. RESULTS: The mean age of enrolled patients was 2.1+/-0.9 months. Based on the three tests, 39 patients (37.1%) were diagnosed with HD, seven patients (6.7%) with AP, and 53 (50.5%) had normal results. Of the 54 patients with transitional zone and a reversed rectosigmoid index on the barium enema, four (7.4%) were patients with AP. The mean age of the AP patients (3.1+/-1.5 months old) was older than the HD children (1.4+/-0.9 months old). The sensitivity of the three tests for HD was 97.4%, 87.2% and 92.3% and the specificity was: 74.2%, 78.8% and 100%, respectively. CONCLUSIONS: In the infants with severe abdominal distention, the incidence of AP mimicking HD was relatively high. Therefore, consideration of AP should be part of the differential diagnosis in infants with severe abdominal distention or findings that mimic HD. For differentiation of these disorders, a rectal suction biopsy is very useful.

I-125 versus Pd-103 for low-risk prostate cancer: long-term morbidity outcomes from a prospective randomized multicenter controlled trial.

BACKGROUND: We tested the hypothesis that the shorter half-life of Pd-103 versus I-125 results in different late radiation-related morbidities following prostate brachytherapy. METHODS: As of June 14th, 2002, 352 of a planned total of 600 patients with 1997 American Joint Committee on Cancer (AJCC) clinical stage T1c-T2a prostatic carcinoma (Gleason grade 2-6, PSA 4-10 ng/mL) had been randomized to implantation with I-125 (144 Gy, TG-43) or Pd-103 (125 Gy, NIST-99). Treatment-related morbidity was monitored by questionnaires based on standard American Urologic Association (AUA) and Radiation Therapy Oncology Group (RTOG) criteria that were mailed at 1, 3, 6, 12, 18, and 24 months after implant. The use of alpha-blockers to relieve obstructive symptoms was not controlled for but was noted at each follow-up point. All patients reported here had a minimum follow-up of 2 years. Dosimetric parameters analyzed included the V100, which was defined as the percentage of the postimplant prostate volume covered by 100% of the prescription dose. Rectal doses were expressed as the R100, defined as the rectal volume (cc) that received at least 100% of the prescription dose. Statistical comparisons were by Student's unpaired t-test at specified follow-up times. RESULTS: The AUA scores peaked at the 1-month postimplant time point for both isotopes and gradually declined. The difference in AUA scores between patients who received I-125 versus those who received Pd-103 was greatest at 1 and 6 months following implantation. At 1 month, I-125 patients had a mean AUA score of 14.8 (+/-9.5) compared with 18.6 (+/-9.8) for the Pd-103 patients (P = 0.0009). By 6 months, mean AUA scores for the I-125 patients had decreased to 12.0 (+/-9.1) compared with 9.9 (+/-8.7) for the Pd-103 patients (P = 0.04). The use of alpha-blockers was similar between groups at all time points. Radiation proctitis (persistent bleeding) occurred in 29 of 314 patients (9%). There was an overall trend toward more proctitis in I-125 patients (P = 0.21). However, only four of the 163 patients (2%) with an R100 below the recommended 1.0 cc developed bleeding, which did not differ between isotopes (P = 0.49). DISCUSSION: Patients treated with Pd-103 had more intense radiation prostatitis in the first month after implantation, but they recovered from their radiation-related symptoms sooner than I-125 patients, consistent with palladium's shorter half-life. The trend toward more proctitis in the I-125 patient group likely reflects their higher R100 values due to less rapid dose fall-off that can be overcome with judicious treatment planning and implant execution.

A phase I/II trial of three-dimensionally planned concurrent boost radiotherapy and protracted venous infusion of 5-FU chemotherapy for locally advanced rectal carcinoma.

BACKGROUND: Improving the response to preoperative therapy may increase the likelihood of successful resection of locally advanced rectal cancers. Historically, the pathologic complete response (pCR) rate has been < approximately 10% with preoperative radiation therapy alone and < approximately 20% with concurrent chemotherapy and radiation therapy. METHODS AND MATERIALS: Thirty-seven patients were enrolled on a prospective Phase I/II protocol conducted jointly at Washington University, St. Louis and the Catholic University of the Sacred Heart, Rome evaluating a three-dimensionally (3D) planned boost as part of the preoperative treatment of patients with unresectable or recurrent rectal cancer. Preoperative treatment consisted of 4500 cGy in 25 fractions over 5 weeks to the pelvis, with a 3D planned 90 cGy per fraction boost delivered once or twice a week concurrently (no time delay) with the pelvic radiation. Thus, on days when the boost was treated, the tumor received a dose of 270 cGy in one fraction while the remainder of the pelvis received 180 cGy. When indicated, nonaxial beams were used for the boost. The boost treatment was twice a week (total boost dose 900 cGy) if small bowel could be excluded from the boost volume, otherwise the boost was delivered once a week (total boost dose 450 cGy). Patients also received continuous infusion of 5-fluorouracil (1500 mg/m(2)-week) concurrently with the radiation as well as postoperative 5-FU/leucovorin. RESULTS: All 37 patients completed preoperative radiotherapy as planned within 32--39 elapsed days. Twenty-seven underwent proctectomy; reasons for unresectability included persistent locally advanced disease (6 cases) and progressive distant metastatic disease with stable or smaller local disease (4 cases). Actuarial 3-year survival was 82% for the group as a whole. Among resected cases the 3-year local control and freedom from disease relapse were 86% and 69%, respectively.Twenty-four of the lesions (65%) achieved an objective clinical response by size criteria, including 9 (24%) with pCR at the primary site (documented T0 at surgery). The most important factor for pCR was tumor volume: small lesions with planning target volume (PTV) < 200 cc showed a 50% pCR rate (p = 0.02). There were no treatment associated fatalities. Nine of the 37 patients (24%) experienced Grade 3 or 4 toxicities (usually proctitis) during preoperative treatment. There were an additional 7 perioperative and 2 late toxicities. The most important factors for small bowel toxicity (acute or late) were small bowel volume (> or = 150 cc at doses exceeding 4000 cGy) and large tumor (PTV > or = 800 cc). For rectal toxicity the threshold is PTV > or = 500 cc. CONCLUSION: 3D planned boost therapy is feasible. In addition to permitting the use of nonaxial beams for improved dose distributions, 3D planning provides tumor and normal tissue dose-volume information that is important in interpreting outcome. Every effort should be made to limit the treated small bowel to less than 150 cc. Tumor size is the most important predictor of response, with small lesions of PTV < 200 cc most likely to develop complete responses.

Argon laser therapy for hemorrhagic radiation proctitis: long-term results.

In chronic radiation proctitis bleeding occurs from mucosal friability and neovascular telangiectasias. Fourteen patients with bleeding from chronic radiation proctitis underwent endoscopic argon laser therapy at 4 to 8 W. The goal of treatment was obliteration of all telangiectasias. The average follow-up was 35 months. Of the 51 procedures, 48 (94%) were performed on outpatients with enema preparation and little or no sedation. A median of three procedures was performed per patient, with two sessions required for initial control of bleeding. Ten patients (71%) required maintenance therapy for recurrent bleeding from telangiectasias that developed after initial therapy. The mean interval between maintenance sessions was 7 months. No immediate or late complications occurred.

Proctitis and proctosigmoiditis--a need to identify the extent of disease in epidemiological surveys.

Proctitis and proctosigmoiditis may be distinct clinical entities. The lesions are restricted to the rectum or extend proximally to involve the sigmoid colon, respectively. Barium enema examination should be normal proximal to the rectum and sigmoid colon. Histology is used merely to confirm the disease process. We provide evidence drawn from a large epidemiological database that significantly more patients with proctitis than proctosigmoiditis followed over a mean period of 11 years became asymptomatic or had their diagnosis revised to a non-inflammatory bowel disease condition (p < 0.05). The 2 groups were well-matched for age, sex, duration of disease and received similar medical treatment. Future epidemiological studies and therapeutic trials should make a distinction between proctitis and proctosigmoiditis.