Growing evidence suggests that spatial dose variations across the rectal surface influence toxicity risk after radiotherapy. Existing methodologies employ a fixed, arbitrary physical extent for rectal dose mapping, limiting their analysis. We developed a method to standardise rectum contours, unfold them into 2D cylindrical surface maps, and identify subregions where higher doses increase rectal toxicities.

Data of 1,048 patients with prostate cancer from the REQUITE study were used. Deep learning based automatic segmentations were generated to ensure consistency. Rectum length was standardised using linear transformations superior and inferior to the prostate. The automatic contours were validated against the manual contours through contour variation assessment with cylindrical mapping. Voxel-based analysis of the dose surface maps for the manual and automatic contours against individual rectal toxicities was performed using Student's t permutation test and Cox Proportional Hazards Model (CPHM). Significance was defined by permutation testing.

Our method enabled the analysis of 1,048 patients using automatic segmentation. Student's t-test showed significance (p < 0.05) in the lower posterior for clinical-reported proctitis and patient-reported bowel urgency. Univariable CPHM identified a 3 % increased risk per Gy for clinician-reported proctitis and a 2 % increased risk per Gy for patient-reported bowel urgency in the lower posterior. No other endpoints were significant.

We developed a methodology that unfolds the rectum to a 2D surface map. The lower posterior was significant for clinician-reported proctitis and patient-reported bowel urgency, suggesting that reducing the dose in the region could decrease toxicity risk.

This retrospective study aimed to evaluate the dosimetric effects of a rectal insertion of Kushen Ningjiao on rectal protection using deformable dose accumulation and machine learning-based discriminative modelling.

Sixty-two patients with cervical cancer enrolled in a clinical trial, who received a Kushen Ningjiao injection of 20 g into their rectum for rectal protection via high-dose rate brachytherapy (HDR-BT, 6 Gy/f), were studied. The cumulative equivalent 2-Gy fractional rectal surface dose was deformably summed using an in-house-developed topography-preserved point-matching deformable image registration method. The cumulative three-dimensional (3D) dose was flattened and mapped to a two-dimensional (2D) plane to obtain the rectal surface dose map (RSDM). For analysis, the rectal dose (RD) was further subdivided as follows: whole, anterior, and posterior 3D-RD and 2D-RSDM. The dose-volume parameters (DVPs) were extracted from the 3D-RD, while the dose geometric parameters (DGPs) and textures were extracted from the 2D-RSDM. These features were fed into 192 classification models (built with 8 classifiers and 24 feature selection methods) for discriminating the dose distributions between pre-Kushen Ningjiao and pro-Kushen Ningjiao.

The rectal insertion of Kushen Ningjiao dialated the rectum in the ambilateral direction, with the rectal column increased from pre-KN 15 cm3 to post-KN 18 cm3 (P < 0.001). The characteristics of DGPs accounted for the largest portions of the top-ranked features. The top-ranked dosimetric features extracted from the posterior rectum were more reliable indicators of the dosimetric effects/changes introduced by the rectal insertion of Kushen Ningjiao. A significant dosimetric impact was found on the dose-volume parameters D1.0cc-D2.5cc extracted on the posterior rectal wall.

The rectal insertion of Kushen Ningjiao incurs significant dosimetric changes on the posterior rectal wall. Whether this effect is eventually translated into clinical gains requires further long-term follow-up and more clinical data for confirmation.

Long-term complications of diabetes include cardiovascular disease, retinopathy, nephropathy, and neuropathy. Diabetic patients with prostate cancer could be at a high risk of radiation-induced acute proctitis following radical radiotherapy. Our aims were to analyse the incidence, severity, and duration of radiation proctitis in diabetic patients treated by radical radiotherapy and combined androgen deprivation for prostate cancer.

On the bases of inclusion and exclusion criteria 716 patients with prostate cancer were retrospectively recruited. Patients were stratified into diabetic patients and non-diabetic patients. The incidence, severity, and duration of proctitis were the main outcomes. A polynomial ordered logistic regression was fitted to determine the influence of diabetes status, age, blood pressures medication, co-morbidities, Gleason score, PSA after treatment, and tumour stage on the grades of proctitis. Time to resolution per year was modelled as a negative binomial generalised linear model.

The overall mean age of patients was 67.44 (SD 6.77) years with a follow-up time of 3.36 (SD 2.05) years. Data exploratory analysis suggested that the only highly significant explanatory variable was the presence or absence of diabetes. Polynomial ordered logistic regression, however, showed that the presence (or not) of diabetes remained as the only significant predictor (t = -2.74; p = 0.0059) of severity of proctitis. A negative binomial generalised linear model showed that both grade of proctitis (z = -17.178; p < 0.001), and diabetes (z = -5.92; p < 0.001), were highly significant predictors of time to resolution.

Diabetic patients were significantly more likely to have proctitis after radical radiation therapy for prostate cancer. Diabetes was significantly associated with an induced risk of radiation induced proctitis and also with deceleration of its resolution.

Radiation proctitis is a common complication after radiotherapy for pelvic malignant tumors. This study was conducted to assess the efficacy of novel almagate enemas in hemorrhagic chronic radiation proctitis (CRP) and evaluate risk factors related to rectal deep ulcer or fistula secondary to CRP. All patients underwent a colonoscopy to confirm the diagnosis of CRP and symptoms were graded. Typical endoscopic and pathological images, risk factors, and quality of life were also recorded. A total of 59 patients were enrolled. Gynecological cancers composed 93.1% of the primary malignancies. Complete or obvious reduction of bleeding was observed in 90% (53/59) patients after almagate enema. The mean score of bleeding improved from 2.17 to 0.83 (P<0.001) after the enemas. The mean response time was 12 days. No adverse effects were found. Moreover, long-term successful rate in controlling bleeding was 69% and the quality of life was dramatically improved (P=0.001). The efficacy was equivalent to rectal sucralfate, but the almagate with its antacid properties acted more rapidly than sucralfate. Furthermore, we firstly found that moderate to severe anemia was the risk factor of CRP patients who developed rectal deep ulcer or fistulas (P= 0.015). We also found abnormal hyaline-like thick wall vessels, which revealed endarteritis obliterans and the fibrosis underlying this disease. These findings indicate that almagate enema is a novel effective, rapid and well-tolerated method for hemorrhagic CRP. Moderate to severe anemia is a risk factor for deep ulceration or fistula.

To assess the efficacy and safety of a modified topical formalin irrigation method in refractory hemorrhagic chronic radiation proctitis (CRP).

Patients with CRP who did not respond to previous medical treatments and presented with grade II-III rectal bleeding according to the Common Terminology Criteria for Adverse Events were enrolled. Patients with anorectal strictures, deep ulcerations, and fistulas were excluded. All patients underwent flexible endoscopic evaluation before treatment. Patient demographics and clinical data, including primary tumor, radiotherapy and previous treatment options, were collected. Patients received topical 4% formalin irrigation in a clasp-knife position under spinal epidural anesthesia in the operating room. Remission of rectal bleeding and related complications were recorded. Defecation, remission of bleeding, and other symptoms were investigated at follow-up. Endoscopic findings in patients with rectovaginal fistulas were analyzed.

Twenty-four patients (19 female, 5 male) with a mean age of 61.5 ± 9.5 years were enrolled. The mean time from the end of radiotherapy to the onset of bleeding was 11.1 ± 9.0 mo (range: 2-24 mo). Six patients (25.0%) were blood transfusion dependent. The median preoperative Vienna Rectoscopy Score (VRS) was 3 points. Nineteen patients (79.2%) received only one course of topical formalin irrigation, and five (20.8%) required a second course. No side effects were observed. One month after treatment, bleeding cessation was complete in five patients and obvious in 14; the effectiveness rate was 79.1% (19/24). For long-term efficacy, 5/16, 1/9 and 0/6 patients complained of persistent bleeding at 1, 2 and 5 years after treatment, respectively. Three rectovaginal fistulas were found at 1 mo, 3 mo and 2 years after treatment. Univariate analysis showed associations of higher endoscopic VRS and ulceration score with risk of developing rectovaginal fistula.

Modified formalin irrigation is an effective and safe method for hemorrhagic CRP, but should be performed cautiously in patients with a high endoscopic VRS.

Chronic radiation proctitis (CRP) occurs up to 20 % of patients after pelvic radiotherapy, with rectal bleeding as the main presenting complaint. Radiofrequency ablation (RFA) has recently been used in the management of Barrett's esophagus, but its efficacy in CRP has to be studied. The aim of this case series was to describe four cases of patients with CRP treated with RFA that demonstrate the efficacy and safety of the technique.

All the procedures were performed with HALO 90 or HALO 90 Ultra ablation catheter fitted on the distal end of a standard flexible endoscope. For each patient, the severity of symptoms was assessed at baseline and after the last treatment session.

At least two sessions of RFA (maximum 4) were necessary, at three-month intervals, to completely control the symptoms. No major complications were observed.

RFA was effective and safe for control bleeding in this case series. Adequately powered randomized controlled trials are needed to establish the safety and efficacy of RFA for CRP.

Chronic radiation proctitis is a long-term complication of radiation therapy for pelvic malignancy. The aim of this study was to compare the efficacy and safety of two treatment regimens, sucralfate or placebo, following argon plasma coagulation (APC) for chronic haemorrhagic radiation proctitis.

A single-centre, randomized, placebo-controlled, double-blind study was performed on patients with haemorrhagic chronic radiation proctitis after irradiation for prostate, uterine, cervical, rectal or vaginal cancer. All patients received APC, and were then randomized to oral sucralfate (6 g twice a day) or placebo treatment for 4 weeks. APC was repeated every 8 weeks if necessary after the first session. Patients were graded clinically and endoscopically according to the Chutkan and Gilinski scales before and at 8 and 16 weeks after initial APC treatment (1.5-2 l/min, 25-40 W) and after 52 weeks (clinical only).

Of 122 patients, 117 completed the entire protocol, with 57/60 in the sucralfate group and 60/62 in the placebo group. At baseline there were no significant differences between the sucralfate and placebo groups. At 1 year, a significant improvement in the clinical scale in both groups occurred compared with baseline. After 16 weeks, the median overall clinical severity scores fell from 4 to 2 points and the median bleeding score from 2 to 0 in both groups.

APC is safe and effective for the management of chronic radiation proctitis. Additional sucralfate treatment did not influence the clinical or endoscopic outcome.

To evaluate the time course of late rectal mucosal changes after prostate cancer radiotherapy (RT).

A rectosigmoidoscopy was performed at 12, 24, and 65 months after RT in 20 patients. Rectal mucosal changes (telangiectasia, congested mucosa, ulceration, stricture, and necrosis) were scored and documented according to the Vienna Rectoscopy Score (VRS, score 0-3).

VRS of 0 and 3, were found in 20% of patients (n = 4) and 5% of patients (n = 1), respectively at all time points. A shift of the VRS from 2 to 1 was found with incidence rates of 60% at 12 months and 20% at 65 months, which is equivalent to an improvement rate of 67%. Laser coagulation was required in 3 patients (15%) with rectal bleeding due to telangiectasia grade ≥2.

Late rectal mucosal changes are frequent after pelvic RT. Generally only the incidence rates corresponding to the initial diagnosis of the complications, independent of subsequent recovery, are reported. The results reported in the present study show that complications often improve over time. Hence, the usual reports of complication rates overestimate the proportion of patients presenting with side effects of certain grades.

Radiation therapy is commonly utilized as a major component in the treatment of pelvic malignancy. Unfortunately, secondary toxicity to the lower gastrointestinal tract can occur. This most commonly affects the rectum, although injuries to the colon and small intestine are not uncommon. The presentation can be acute or chronic, and different mechanisms are responsible for each. Symptomatology is quite variable but can result in significant compromise for the patient. Numerous preventive and treatment strategies have been applied to this disease process. This article presents a summary of the current knowledge regarding radiation injury to the lower gastrointestinal tract with special emphasis on treatment options for radiation proctitis.

Chronic radiation proctopathy occurs in 5 to 20% of patients receiving radiation therapy, with rectal bleeding as its most common presentation. Although formalin treatment for rectal bleeding is promising, improvement is possible. Given the success of vitamin A in other radiation-induced treatments, we studied the efficacy of combining formalin with vitamin A in controlling bleeding symptoms of chronic radiation proctopathy.

A retrospective review (1993-2007) was performed of patients presenting with features of chronic radiation proctopathy. Formalin 8% in a buffered solution was applied to the affected mucosa with use a tip applicator, and 10,000 units of vitamin A were given orally on a daily basis. Formalin treatments were repeated at three-week to four-week intervals until symptoms resolved.

A comparison was made between patients who received formalin alone (n = 30) and those who received formalin in combination with vitamin A (n = 34). The 64 patients had a mean age of 79 years (range, 54-90 years). The combination group required fewer treatments (mean, 1.9) and a shorter time (11 weeks) for resolution of symptoms compared with the formalin-alone group (mean, 5.2 and 31 weeks, respectively) (P < 0.001). The overall success rate in controlling bleeding was only 64% in the formalin-alone group when compared with 94% in the combination group.

When vitamin A was added to the regimen, a significant reduction was observed in the number of treatments and the time needed for resolution of symptoms, and there was an increased overall success rate. This combination represents a simple, effective, and well tolerated method of controlling hemorrhagic chronic radiation proctopathy.

To evaluate the Vienna Rectoscopy Score (VRS) as a feasible and effective tool for detecting and classifying pathologic changes in the rectal mucosa after radiotherapy (RT) for prostate cancer, and, also, to correlate its findings with the European Organization for Research and Treatment of Cancer (EORTC)/Radiation Therapy Oncology Group (RTOG) score for late rectal toxicity.

A total of 486 patients with localized prostate cancer underwent external-beam RT up to 70 or 74 Gy within an Austrian-German prospective multicenter trial. In 166 patients, voluntary rectal sigmoidoscopy was performed before and at 12 and/or 24 months after RT. Pathologic findings such as telangiectasia, congested mucosa, and ulcers were graded (Grades 0-3) and summarized according to the VRS. Late rectal side effects (EORTC/RTOG) were documented and correlated with the corresponding VRS.

Before RT, 99% had a VRS score of 0. The median follow-up was 40 months. Overall, a late rectal side effects grade or score 1-3 was detected in 43% by EORTC/RTOG compared with 68% by VRS (p < 0.05). Grades 0, 1, 2, and 3 late rectal side effects were found using EORTC/RTOG in 57%, 11%, 28%, and 3%, respectively; the corresponding percentages were 32%, 22%, 32%, and 14% for a VRS of 0, 1, 2, and 3, respectively. A significant coherence between the VRS and EORTC/RTOG was found (p < 0.01).

The VRS is a feasible and effective tool for describing and classifying pathologic findings in the rectal mucosa after RT within a multicenter trial. The VRS and EORTC/RTOG showed a high coherence. However the VRS was significantly more sensitive.

To compile and review data on radiation proctopathy in the treatment of prostate cancer with respect to epidemiology, clinical manifestations, pathogenesis, risk factors, and treatment.

Medical literature databases including PubMed and Medline were screened for pertinent reports, and critically analyzed for relevance in the scope of our purpose.

Rectal toxicity as a complication of radiotherapy has received attention over the past decade, especially with the advent of dose-escalation in prostate cancer treatment. A number of clinical criteria help to define acute and chronic radiation proctopathy, but lack of a unified grading scale makes comparing studies difficult. A variety of risk factors, related to either radiation delivery or patient, are the subject of intense study. Also, a variety of treatment options, including medical therapy, endoscopic treatments, and surgery have shown varied results, but a lack of large randomized trials evaluating their efficacy prevents forming concrete recommendations.

Radiation proctopathy should be an important consideration for the clinician in the treatment of prostate cancer especially with dose escalation. With further study of possible risk factors, the advent of a standardized grading scale, and more randomized trials to evaluate treatments, patients and physicians will be better armed to make appropriate management decisions.

The aim of this study was to investigate prospectively the rectal wall (Rwall) spatial dose distribution, toxicity, and mucosal changes after prostate cancer radiotherapy with or without an endorectal balloon (ERB).

A total of 24 patients with ERB and 24 without ERB (No-ERB) were treated with three-dimensional conformal radiotherapy (3D-CRT) to a dose of 67.5 Gy. The Rwall was divided into 16 mucosal areas and Rwall dose surface maps were constructed. After 3 months, 6 months, 1 year, and 2 years a rectosigmoidoscopy was performed, and each mucosal area was scored on telangiectasia, congestion, ulceration, stricture, and necrosis. Late rectal toxicity was correlated with the endoscopic findings.

The ERB significantly reduced the Rwall volume exposed to doses >40 Gy. Late rectal toxicity (grade >or=1, including excess of bowel movements and slight rectal discharge) was reduced significantly in the ERB group. A total of 146 endoscopies and 2,336 mucosal areas were analyzed. Telangiectases were most frequently seen and appeared after 6 months. At 1 and 2 years, significantly less high-grade telangiectasia (T 2-3) was observed in the ERB group at the lateral and posterior part of the Rwall. In mucosal areas exposed to doses >40 Gy, less high-grade telangiectases (T 2-3) were seen in the ERB group compared with the No-ERB group.

An ERB reduced the Rwall volume exposed to doses >40 Gy, resulting in reduction of late rectal mucosal changes and reduced late rectal toxicity. Although further analysis is needed, these data suggest an ERB-induced increased tolerance for late Rwall damage.

Radiation proctitis is a common complication following radiation therapy for pelvic malignancies. This is associated with significant morbidity which adversely affects the quality of life. Local application of formalin has been used effectively in the treatment of radiation proctitis.

Thirty patients with haemorrhagic radiation proctitis who underwent endoluminal application of 4% formalin between January 1998 to October 2002 were followed up prospectively to assess the efficacy of the treatment.

The follow up ranged from 5 to 36 months (mean 18.1 months). Nineteen (63.3%) patients had complete response to formalin application while 7 (23.3%) patients had partial response. There were 4 (13.3%) failures. No procedure related complication was observed.

Local application of formalin is a simple, safe, inexpensive and fairly effective outpatient treatment modality for chronic radiation proctitis.

Cluster models are newly developed normal-tissue complication probability models in which the spatial aspects of radiation-induced injury are taken into account by considering the size of spatially contiguous aggregates of damaged tissue units. The purpose of this study was to test the validity of a two-dimensional cluster model of late rectal toxicity based on maximum cluster size of damage to rectal surface.

A paired case-control study was performed in which each of 9 patients experiencing Grade 2 or higher late rectal toxicity after intensity-modulated radiation therapy of localized prostate cancer was paired with a patient having a similar rectal dose-surface histogram but free of rectal toxicity. Numeric simulations were performed to determine the distribution of maximum cluster size on each rectal surface for each of many different choices of possible model parameters.

Model parameters were found for which patients with rectal toxicity were consistently more likely to have a significantly larger mean maximum cluster size than their matched controls. These parameter values correspond to a 50% probability of tissue-unit damage at doses near 30 Gy.

This study suggests that a cluster model based on maximum cluster size of damage to rectal surface successfully incorporates spatial information beyond that contained in the rectal dose-surface histogram and may therefore provide a useful new tool for predicting rectal normal-tissue complication probability after radiotherapy.

To identify endoscopic pathological findings prior to radiotherapy and a possible correlation with acute or chronic rectal side effects after three-dimensional conformal radiotherapy (3D-CRT) for prostate cancer.

Between 03/99 and 07/02, a total of 298 patients, who consented in a voluntary rectoscopy prior to radiotherapy were included into the analysis. Patients were treated with a total dose of either 70 or 74 Gy. Pathological rectoscopic findings like hemorrhoids, polyps or diverticula were documented. Acute and late rectal side effects were scored using the EORTC/RTOG score.

The most frequent pathological endosopic findings were hemorrhoids (35%), polyps (24%) and diverticula (13%). Rectal toxicity was mostly low to moderate. Grade 0/1 cumulative acute and late rectal side effects were 82 and 84%, grade 2 were 18 and 17%, respectively. We could not identify any correlation between preexisting pathological findings and rectal side effects by statistical analysis.

There is no evidence that prostate cancer patients presenting with endoscopic verified pathological findings in the rectal mucosa at diagnosis are at an increased risk to develop rectal side effects when treated with 3D-CRT of the prostatic region.

To investigate dysfunction caused by unwanted radiation to the anal-sphincter region and the rectum.

A questionnaire assessing bowel symptoms, sexual function, and urinary symptoms was sent to 72 patients with clinically localized prostatic adenocarcinoma treated by external beam radiation therapy at the Radiumhemmet, Karolinska Hospital, in Stockholm, Sweden, 2-4 years after treatment. The mean percentage dose-volume histograms for patients with and without the specific symptom were calculated.

Of the 65 patients providing information, 9 reported fecal leakage, 10 blood and mucus in stools, 10 defecation urgency, and 7 diarrhea or loose stools. None of the 19 and 13 patients who received, respectively, a dose of > or =35 Gy to < or =60% or > or =40 Gy to < or =40% of the anal-sphincter region volume reported fecal leakage (p < 0.05). In dose-volume histograms, a statistically significant correlation was found between radiation to the anal-sphincter region and the risk of fecal leakage in the interval 45-55 Gy. There was also a statistically significant correlation between radiation to the rectum and the risk of defecation urgency and diarrhea or loose stools in the interval 25-42 Gy. No relationship was found between anatomic rectal wall volume and the investigated late effects.

Although the limited data in this study prevent the definition of a conclusive threshold regarding volume and dose to the anal-sphincter region and untoward morbidity, it seems that careful monitoring of unnecessary irradiation to this area should be done because it can potentially help reduce the risk of adverse effects, such as fecal leakage. Future studies should pay more attention to the anal-sphincter region and help to more rigorously define its radiotherapeutic tolerance.

To correlate long-term colorectal dysfunctions following radical radiotherapy for bladder or prostate cancer with clinical parameters and dose-volume histogram parameters of the small intestine, rectum, and anal canal volume.

Seventy-one patients previously treated for bladder or prostate cancer were interviewed following CT-based radiotherapy of 60-70 Gy with questions concerning long-term colorectal dysfunctions. Median follow-up time was 30 months (range 12-109 months). Clinical parameters and parameters from the dose-volume histograms were correlated with colorectal dysfunctions (Spearman's test). Median and quartile values of all parameters were used as cut-off values for statistical analyses. A logistic regression model was used for analysis of urgency and incontinence in relation to median or maximum radiation dose to the anal canal volume.

Rectum length, volume and several dose-volume parameters from the anal canal volume and rectal volume were correlated with late organ dysfunctions. In a logistic model, fecal urgency and incontinence were dependent of dose-volume parameters from the anal canal volume. No relation between age or follow-up time and late effects were found. Dose-volume parameters of the small intestine were not related to any late dysfunctions.

A relationship between several late anorectal dysfunctions and dose-volume parameters from the rectum and anal canal volume was demonstrated. It is recommended to exclude the anal canal volume from the high dose-volume and to apply rectal shielding whenever possible to prevent late anorectal dysfunctions.

Chronic radiation proctitis represents a challenging condition seen with increased frequency due to the common use of radiation for treatment of pelvic cancer. Hemorrhagic radiation proctitis represents the most feared complication of chronic radiation proctitis. There is no consensus for the management of this condition despite the great number of clinical approaches and techniques that have been employed. Rectal resection represents an available option although associated with high morbidity and risk of permanent colostomy. The effectiveness of nonoperative approaches remains far from desirable, and hemorrhagic recurrence represents a major drawback that leads to a need for consecutive therapeutic sessions and combination of techniques. We conducted a critical review of published reports regarding conservative management of hemorrhagic chronic radiation proctitis. Although prospective randomized trials about hemorrhagic radiation proctitis are still lacking, there is enough evidence to conclude that topical formalin therapy and an endoscopic approach delivering an argon plasma coagulation represent available options associated with elevated effectiveness for interruption of rectal bleeding in patients with chronic radiation proctitis.

The combination of radiation, fluorouracil, and oxaliplatin in locally advanced rectal cancer has been shown to be feasible in a phase I trial. The purpose of this phase II trial was to assess tolerance and efficacy of this regimen in a preoperative setting.

Between May 2000 and October 2001, 40 operable patients were entered onto the study. Radiotherapy was delivered with a three-field technique to a dose of 50 Gy over 5 weeks with a concomitant boost approach. Two cycles of chemotherapy were given synchronously on weeks 1 and 5, with oxaliplatin 130 mg/m(2) on day 1 followed by 5-day continuous infusion of fluorouracil 350 mg/m(2) and L-folinic acid 100 mg/m(2). Surgery was planned 5 weeks later.

All patients completed treatment without modification except one who experienced grade 3/4 toxicity. Grade 3 toxicity was seen in seven patients. Surgery was performed in all patients after a mean interval time of 5 weeks. An objective clinical response was seen in 30 patients (75%). Sphincter-saving surgery was possible in 26 patients. No postoperative deaths occurred. In four patients (10%), a reoperation was necessary (anastomotic fistula, n = 2; pelvic abscess, n = 2). In six cases the operative specimen was sterilized (15%), and in 12 cases (30%), only few residual cells were detected.

Such a combined preoperative chemoradiotherapy and oxaliplatin-containing regimen is well tolerated with no increase in surgical toxicity. The good response rate observed warrants its use in further clinical trials.

Surgery is the standard treatment for rectal adenocarcinoma. The tumour is resistant to radiation; doses above 80 Gy are necessary and have to be delivered by endocavitary irradiation. Contact radiotherapy is a basic method of delivering a high dose in a small volume. Brachytherapy can be used to deliver a boost of radiation into a residual lesion. External-beam radiotherapy can be used to supplement the dose to the deep part of the primary tumour and to the perirectal lymph nodes. T1N0 tumours have been treated by contact radiotherapy, and local control was achieved in 85-90% of patients with no severe toxic effects. Combined endocavitary irradiation and external-beam irradiation can achieve local control in 80% of patients with T2 tumours and 60% of patients with T3 tumours with only moderate toxic effects and a 60% 5-year overall survival. Radiotherapy alone is suitable for patients with T1N0 lesions (contact radiotherapy) or patients with T2-3 (combined endocavitary and external-beam radiotherapy) who cannot undergo surgery. For T2 or early T3 tumours of the lower rectum requiring surgery and a permanent colostomy, combined irradiation can be used as a first-line treatment in an attempt to avoid abdominoperineal amputation.

Accurate modeling of late rectal reactions needs the collection of individual 3D dose-volume data (i.e. DVH) as well as clinical information of large cohorts of patients. The possibility of collecting a large number of patients with many different dose-volume combinations is very suitable for this purpose.

The purpose of the study is to search for significant correlation between dose-volume histograms/dose statistics of the rectum and late rectum bleeding.

Data from three institutions for 402 patients previously treated for prostate cancer with three to four field techniques, were retrospectively pooled and were collected with a number of clinical and physical parameters, including DVHs of the rectum (including filling). Patients with large air/fecal content in the rectum during planning computerized tomography (CT) scan were excluded from the analysis (n = 74). Out of 328 patients, 229 patients received an ICRU dose between 70 and 76Gy and the current analysis is referred to this subgroup of patients (median follow up: 30 months, range: 12-85 months). Out of these 229 patients, 189 patients were treated with conformal techniques. Rectum was contoured from the anal verge up to the sigmoid flessure by one observer for each institution. Dosimetric and contouring consistencies between the three institutions were previously investigated and the impact on DVHs was found to be quite modest for the purposes of the study. Median/quartile values of all parameters were considered as cut-off values for statistical analysis. We considered as bleeders those patients who experienced grades II-III late bleeding (modified RTOG scoring scale).

Twenty two of 229 patients experienced > or =grade II late bleeding (30 months actuarial incidence: 10.7%). Significant correlation between a number of parameters and late bleeding was found (log-rank test). With regard to DVH, all median and third quartile values for V50-V70 were found to be significantly associated with an increased risk of rectal bleeding, if excepting the median value of V70. Based on the results of univariate analysis, the patients were divided into two groups: 'high risk', with at least one value above quartiles in the range V50-V60 (V50: 70%, V55: 64%, V60: 55%); 'low risk', the remaining patients. The 30 months actuarial rates of bleeding were 19.2 and 5.9% for the 'high' and the 'low' risk group, respectively (P = 0.0003 log-rank test). A multivariate analysis (Cox regression model) including 'DVH grouping' and the main remaining variables (age, previous prostatectomy, diabetes, hypertension, adjuvant hormonal therapy, rectum volume and ICRU dose) showed that 'DVH grouping' is the most predictive parameter (P = 0.005) together with adjuvant hormonal therapy (P = 0.025) and ICRU dose (P = 0.06).

Our data confirm the role of the rectal DVH in separating groups of patients having prostate radiotherapy in low and high risk of developing late bleeding. Based on these results, V50 below 60-65% and V60 below 50-55% seem to be the robust cut-off values to keep the risk of developing late rectal bleeding reasonably low. However, due to the 'heterogeneity' of the considered population, the results found should be applied with caution in 'more homogeneous' groups of patients. The association of adjuvant hormone deprivation seems to be associated with an increased risk of rectal toxicity; the mechanism for this effect should be a focus of further research.

Chronic radiation proctitis, a well described complication of pelvic radiation therapy, can result in severe bleeding that is refractory to conventional treatment. Argon plasma coagulation is an effective treatment for hemorrhagic lesions of the gastrointestinal tract. The aim of this study was to assess the efficacy and safety of argon plasma coagulation in the management of severe radiation proctitis resistant to medical treatment.

Eleven patients (10 males) aged between 54 and 86 years (mean +/- standard error of the mean, 73 +/- 3 years), with chronic radiation proctitis after radiotherapy for prostate (n = 9), uterine (n = 1) or rectal (n = 1) cancer were enrolled in this prospective study. Traditional therapies had failed including mainly topical steroids, 5-aminosalicylic acid and sometimes sucralfate. All patients had active bleeding from diffuse telangiectasias responsible for chronic anemia and seven of them required blood transfusions. The mean duration of the sessions was 20 minutes and one to five sessions (mean, 3.2 +/- 0.4), usually without anesthesia, were required to stop bleeding. Mean follow-up time was 19 +/- 2 (range, 7-30) months.

Rectal bleeding disappeared in nine patients and was greatly reduced in two. All the patients were free of transfusions during the mean follow-up of 19 months. The mean hemoglobin level was 7.7 +/- 2.8 g/dl at the first session and increased significantly (P = 0.003) to 11.5 +/- 2.6 g/dl after treatment. In two patients, a rectal stenosis appeared 7 and 11 months after the first session.

Argon plasma coagulation is a simple, inexpensive and effective treatment for severe refractory radiation proctitis with telangiectasias. Follow-up supervision is in progress to evaluate long term benefits and the risk of rectal stenosis.

Increasing use of radiation therapy in pelvic malignancy has led to an increase in the incidence of chronic radiation proctitis. The commonest presenting complaint is rectal bleeding.

A comprehensive MEDLINE search was undertaken for all articles relating to radiation proctitis.

The natural history of the disease is poorly documented but improvement is likely in milder forms, with persistence of symptoms in more severe forms. The pathological manifestations of the disease are summarized with particular comparison to acute radiation proctitis. The common clinical presentations and the principles of assessing patients with radiation-induced proctitis will be reviewed. The present article also reviews current treatment options, with particular reference to newer endoscopic therapies and surgical principles of management.

The initial therapy for problematic rectal bleeding related to radiation-induced proctitis shoud be endoscopic therapy with argon plasma coagulation or topical formalin therapy. Surgery is reserved as a last resort for resistant rectal bleeding and for complicated radiation-induced strictures and fistulas.

Radiation proctopathy is a common unfortunate complication following radiation therapy of pelvic malignancies. Symptoms of chronic radiation proctopathy include haematochezia, urgency, constipation, tenesmus, diarrhoea and rectal pain. Currently, a wide variety of pharmacological options, endoscopic cautery techniques and surgical procedures have been proposed for the treatment of chronic radiation proctopathy. Although these have been proposed primarily as treatment for rectal bleeding, the control of other symptoms has been noted with some of these agents. Pharmacological options include 5-aminosalicylic acid preparations, coticosteroid enemas, sucralfate (oral, enemas), formalin, short chain fatty acid enemas, oestrogen/progesterone, hyperbaric oxygen, antioxidants, sodium pentosan polysulphate and misoprostol rectal suppositories. Of these, sucralfate and formalin therapy appear to be effective for bleeding control. Misoprostol rectal suppositories and oral sucralfate may be useful in the prevention of acute and chronic symptoms of radiation proctopathy. Endoscopic cautery techniques have included the use of Nd:YAG laser and argon laser for coagulation of bleeding neovascular telangiectasias. Argon plasma coagulation offers a safe non-contact method of delivering haemostasis which has proven to be particularly useful in targeting difficult to reach lesions tangentially. Surgery is generally reserved for severe refractory cases involving ongoing haemorrhage, obstruction, stricture formation, fistulas and perforation. Given that formal randomized placebo-controlled studies are lacking for most treatments, the management of these patients is often challenging and unclear. Hence, there is a need for more research and education on radiation proctopathy.

Predicting late-term normal-tissue complication probability (NTCP) after radiotherapy is an important factor in the optimization of conformal radiotherapy. We propose a new NTCP model, based on the properties of the high dose region. The principal assumption of the new model is that a whole-organ complication will occur when the radiation damage to a normal organ volume (a portion of the total organ) exceeds a threshold value. The dose threshold for complications varies with the size of the volume (percent of the total organ). We hypothesize that a complication occurs if the complication threshold is exceeded for any organ volume. We used the average dose to a volume as a measure of radiation damage to that volume. Also, we used the power law to scale the average dose to various organ volumes to a whole-organ equivalent dose, and to identify the volume with the most harmful dose-size combination-the critical volume. We used a logistic distribution to calculate the probability that the patient will develop a complication, given the dose delivered to the critical volume. We used a maximum likelihood fit to estimate the model parameters for late-term rectal complications in a set of patients treated for prostate carcinoma with external photon beam radiotherapy (EBRT). Good correspondence was found between the experimental data and the model predictions.

To analyze the frequency and clinical importance of proctitis and hematochezia after radiation therapy for prostate cancer.

Of 63 patients with prostate cancer treated with curative intent by a single radiation oncologist between July 1, 1993, and December 31, 1997, 30 were asymptomatic, but 33 had heme-positive digital rectal examination (DRE) results or hematochezia at routine follow-up. Twenty-six of these patients underwent endoscopy of the sigmoid colon or colon for evaluation of these symptoms. Median doses of 60.0 Gy at postoperative radiation therapy and 68.4 Gy at definitive radiation therapy were delivered to four fields daily by using blocking customized on the basis of computed tomographically documented evidence of disease. The Fisher exact test and the Kaplan-Meier method were used to analyze the results.

The frequency of rectal bleeding approached 80% at 3 years after radiation therapy in definitively treated patients. Only 14 patients had proctitis: eight as the only sign, and six in association with other disease. Six patients had other disease without proctitis, and four patients had normal examination findings. The frequency of rectal bleeding in the presence of proctitis was similar to that in the presence of other disease (Fisher exact test, P =.68).

Hematochezia or positive DRE findings are frequent sequelae of definitive radiation therapy for prostate cancer; however, causes other than proctitis are often documented at endoscopy. Symptomatic individuals warrant rigorous evaluation to rule out serious coexistent disease.

Radiation-induced proctosigmoiditis is a serious complication of pelvic radiation therapy. Rectal bleeding occurs among 6% to 8% of these patients and is extremely difficult to manage. Pharmacotherapy is generally ineffective, whereas surgical treatment is associated with high morbidity and mortality. Argon plasma coagulation is a new method of noncontact electrocoagulation well suited for hemostasis of large bleeding areas.

From December 1996 through March 1998, we used argon plasma coagulation to treat 28 patients with hemorrhagic radiation-induced proctosigmoiditis. Indications for treatment were anemia (n = 18) and persistent bleeding despite pharmacotherapy (n = 10). Argon flow and electrical power were set at 1.5 L/min and 50 W. The severity of rectal bleeding was graded from 0 to 4 (highest), and hemoglobin levels were recorded before and after treatment.

Eighty-two therapeutic sessions were performed (median 2.9 sessions per patient). The severity score for rectal bleeding dropped at least 1 point for all but 2 patients, and the mean value decreased from 2.96 to 0.68. Average hemoglobin level increased 1.2 gm/dL (1.9 gm/dL among anemic patients). No serious complications were observed.

Argon plasma coagulation appears to be a simple, safe, and effective technique in the management of hemorrhagic radiation-induced proctosigmoiditis.

To assess the prevalence of combined fecal and urinary incontinence.

A cross-sectional, community-based study.

Olmsted County, Minnesota.

Men (n = 778) and women (n = 762), aged 50 years or older, selected randomly from the population.

Participants completed a previously validated self-administered questionnaire that assessed the occurrence of fecal and urinary incontinence in the previous year.

The age-adjusted prevalence of incontinence was 11.1% (95% Confidence Interval (CI), 8.8-13.5) in men and 15.2% (95% CI, 12.5-17.9) in women for fecal incontinence; 25.6% (95% CI, 22.5-28.8) in men and 48.4% (95% CI, 44.7-52.2) in women for urinary incontinence; and 5.9% (95% CI, 4.1-7.6) in men and 9.4% (95% CI, 7.1-11.6) in women for combined urinary and fecal incontinence. The prevalence of fecal incontinence increased with age in men but not in women, from 8.4% among men in their fifties to 18.2% among men in their eighties (P for trend = .001). For women, the prevalence increased from 13.1% among 50-year-old women to 20.7% among women 80 years or older (P for trend = .5). Among persons with fecal incontinence, the prevalence of concurrent urinary incontinence was 51.1% among men and 59.6% among women (P = .001 and P = .003, respectively). Cross-sectionally, the age-adjusted, relative odds of fecal incontinence among persons with urinary incontinence was greater in men than in women (Odds Ratio (OR) = 3.0; 95% CI, 1.9-4.8 in men and OR = 1.8; 95% CI, 1.2-2.7 in women, P = .04).

These findings suggest that persons with one form of incontinence are likely to have the other form as well. Despite the higher prevalence of urinary and fecal incontinence among women, the association between fecal incontinence and urinary incontinence was stronger among men than women. This finding, and the significant association between fecal incontinence and age observed in men but not in women, suggest that the etiologies may be more closely linked in men than in women.

Radiation proctitis is a complication of radiotherapy for malignant pelvic disease. Argon beam coagulation is a new and rapidly evolving technology that permits a "no-touch" electrocoagulation of diseased tissue.

We analyzed retrospectively the records of 7 patients with prostatic and endometrial cancers treated with irrradiation (median radiation dose was 6840 cGy, range 2400 to 7200 cGy). The median time to onset of symptoms after the conclusion of radiotherapy was 20 months (range 16 to 48 months); symptoms consisted of rectal bleeding and tenesmus in all patients. The patients underwent argon beam coagulation after colonoscopic evaluation. The usual treatment interval was 3 weeks (range 1 to 3 weeks).

A median of 2 treatment sessions (range 2 to 4) was necessary for complete symptom relief. All interventions were well tolerated without complications. During follow-up (median 24 months, range 18 to 24 months), there was no recurrence of symptoms (bleeding, tenesmus).

Argon beam coagulation is a safe, well tolerated, and effective treatment option in symptomatic radiation proctitis.

The incidence of chronic, radiation-induced proctitis is between 2% and 5 %. There is not a direct relationship between the incidence of acute radiation proctitis and the subsequent development of chronic proctitis. The treatment for this condition should proceed in a step-wise fashion from conservative therapy such as antidiarrhea medication, topical steroids, sucralfate enemas, and iron replacement to more aggressive treatment in those who do not respond. In the case of persistent rectal bleeding, laser therapy and formalin instillation should be tried prior to surgical intervention. If surgery is necessary, a transverse or descending colostomy should be tried. Aggressive surgery such as rectal resection and colo-anal anastomosis is associated with significant morbidity and mortality and should be reserved as a last resort measure.

Late rectal morbidity has been observed in 2%-25% of patients treated with radiotherapy using curative doses for prostate, cervix and rectal cancers. The major encountered clinical pictures are rectal proctitis, rectal/anal strictures, rectal bleeding, ulcers and fistula. Some may alter the patient's lifestyle while other may induce death. Recommendations concerning the clinical practice are described. The treatment of these late rectal effects include nutritional recommendations, laser, formalin application, and surgery.