Acute toxicity of conformal high dose interstitial brachytherapy boost in prostate cancer

Over the past few years, brachytherapy has become more and more common in the treatment of prostate cancer, largely thanks to the reduced amount of acute and chronic side effects. At the same time, brachytherapy also allows dose escalation, resulting in significant improvements in the treatment results. From August 2004 to June 2005, we irradiated 40 patients suffering from T1c-T3a prostate cancer. All of the patients underwent external beam radiotherapy with a median dose of 45-50.4 Gy and a conformal high dose interstitial brachytherapy boost (two fractions, 8 Gy per fraction). The patients were divided into three groups: low risk of recurrence (11 patients - 27.5%), intermediate risk (14 patients - 35%) and high risk (15 patients - 37.5%). The medium age of the patients was 68.7 years (between 55 and 77). Hormonal treatment was carried out 17 patients (42.5%). We evaluated the quality of each implantation, including the maximum urethral and rectal dose. The calculated doses were compared with measurements by in vivo dosimetry. Acute toxicity was evaluated in all of the patients according to the Radiation Therapy Oncology Group (RTOG) scale. Each of the patients completed an International Prostatic Symptom Score (IPSS) questionnaire. Acute genitourinary morbidity grade 1 was recorded in 37.5% of patients; grade 2 in 15% of patients. Urine retention in one of the patients resulted in the need to perform an epicystostomy. According to the IPSS score, the majority of patients (90%) experienced an improvement in symptoms related to quality of life. Grade 1 acute gastrointestinal toxicity was recorded in 40% of the patients. Grades 2-4 were not recorded. Here, we show that the combination of external beam radiotherapy and high dose rate (HDR) brachytherapy in the treatment of early prostate cancer to be feasible and well tolerated. Acute toxicity was low and scarcely influenced the quality of life. Among the risk factors of genitourinary toxicity was the volume of the prostate. For gastrointestinal toxicity, risk factors included the combination of HDR brachytherapy and external beam radiotherapy to the pelvis, as well as hormonal treatment.     

Preoperative Chemoradiation for Rectal Cancer Causes Prolonged Pudendal Nerve Terminal Motor Latency

Purpose A worsened anorectal function after chemoradiation for high-risk rectal cancer is often attributed to radiation damage of the anorectum and pelvic floor. Its impact on pudendal nerve function is unclear. This prospective study evaluated the short-term effect of preoperative combined chemoradiation on anorectal physiologic and pudendal nerve function. Methods Sixty-six patients (39 men, 27 women) with localized resectable (T3, T4, or N1) rectal cancer were included in the study. All patients received 45 Gy (1.8 Gy/day in 25 fractions) over five weeks, plus 5-fluorouracil (350 mg/m²/day) and leucovorin (20 mg/m²/day) concurrently on days 1 to 5 and 29 to 33. Patients who had rectal cancer with a distal margin within 6 cm of the anal verge had the anus included in the field of radiotherapy (Group A, n = 26). Patients who had rectal cancer with a distal margin 6 to 12 cm from the anal verge had shielding of the anus during radiotherapy (Group B, n = 40). The Wexner continence score, anorectal manometry and pudendal nerve terminal motor latency were assessed at baseline and four weeks after completion of chemoradiation. Results The median Wexner score deteriorated significantly (P < 0.0001) from 0 to 2.5 for both Groups A (range, 0–8) and B (range, 0–14). The maximum resting anal pressures were unchanged after chemoradiation. The maximum squeeze anal pressures were reduced (mean = 166.5–157.5 mmHg) after chemoradiation. This change was similar in both Groups A and B. Eighteen patients (Group A = 7, Group B = 11) developed prolonged pudendal nerve terminal motor latency after chemoradiation. These 18 patients similarly had a worsened median Wexner continence score (range, 0–3) and maximum squeeze anal pressures (mean = 165.5–144 mmHg). The results obtained were independent of tumor response to chemoradiation. Conclusions Preoperative chemoradiation for rectal cancer carries a significant risk of pudendal neuropathy, which might contribute to the incidence of fecal incontinence after restorative proctectomy for rectal cancer. Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Philadelphia, Pennsylvania, April 30 to May 5, 2005.     

Systematic review: anal and rectal changes after radiotherapy for prostate cancer

Purpose

Pelvic radiotherapy may lead to changes of anorectal function resulting in incontinence-related complaints. The aim of this study was to systematically review objective findings of late anorectal physiology and mucosal appearance after irradiation for prostate cancer.

Methods

MEDLINE, EMBASE, and the Cochrane library were searched. Original articles in which anal function, rectal function, or rectal mucosa were examined ≥3 months after EBRT for prostate cancer were included.

Results

Twenty-one studies were included with low to moderate quality. Anal resting pressures significantly decreased in 6 of the 9 studies including 277 patients. Changes of squeeze pressure and rectoanal inhibitory reflex were less uniform. Rectal distensibility was significantly impaired after EBRT in 7 of 9 studies (277 patients). In 4 of 9 studies on anal and in 5 of 9 on rectal function, disturbances were associated with urgency, frequent bowel movements or fecal incontinence. Mucosal changes as assessed by the Vienna Rectoscopy Score revealed telangiectasias in 73 %, congestion in 33 %, and ulceration in 4 % of patients in 8 studies including 346 patients, but no strictures or necrosis. Three studies reported mucosal improvement during follow-up. Telangiectasias, particularly multiple, were associated with rectal bleeding. Not all bowel complaints (30 %) were related to radiotherapy.

Conclusions

Low to moderate quality evidence indicates that EBRT reduces anal resting pressure, decreases rectal distensibility, and frequently induces telangiectasias of rectal mucosa. Objective changes may be associated with fecal incontinence, urgency, frequent bowel movements, and rectal bleeding, but these symptoms are not always related to radiation damage.     

Clinical effects of preoperative radiation therapy on anorectal function after proctectomy and colonic J-pouch-anal anastomosis

PURPOSE: Preoperative radiotherapy is increasingly used for certain rectal cancers, although some evidence suggests that it may adversely affect anorectal function. Reconstruction with a colonic J-pouch-anal anastomosis after complete proctectomy is thought to improve function, but few published data on pouch function after radiation exists. The aim of our study was to compare long-term bowel habits in patients receiving preoperative radiation for rectal cancer followed by colonic J-pouch-anal anastomosis with those of patients having similar rectal cancer surgery without radiation. METHODS: Patients (n = 125) having undergone colonic J-pouch-anal anastomosis for rectal cancer, of whom 28 had preoperative radiotherapy and 97 did not, responded to a detailed questionnaire about their bowel habits at least 12 months after surgery, with a mean (± standard deviation) interval of 64 (±42) months. Radiation was administered preoperatively as a short (25 Gy over 5 days, n = 22) or long (45 Gy over 4 weeks, n = 6) course. All patients had colonic J-pouch-anal anastomosis with manual anastomosis at or immediately above the dentate line. RESULTS: Except for tumor stage, no preoperative difference was observed between the two groups. The number of bowel movements per 24 hours in patients with and without radiation was 1.8 (±0.8) and 1.8 (±1.5), respectively (P > 0.05). In the irradiated group, diarrhea (39 vs. 13 percent, P = 0.005) and nocturnal defecation (36 vs. 15 percent, P = 0.03) were more frequent than in the nonirradiated group. No other significant difference existed between groups with regard to stool clustering, use of protective pads, ability to defer evacuation >15 minutes, ability to evacuate the bowel within 30 minutes, incontinence score, use of medications, or dietary restriction. CONCLUSION: Preoperative radiotherapy followed by proctectomy and colonic J-pouch-anal anastomosis significantly increased nocturnal defecation frequency and diarrhea compared with similar nonirradiated patients but had no influence on the other bowel-habit parameters studied.     

Long-Term Effect of Preoperative Radiation Therapy on Anorectal Function

Purpose Preoperative radiotherapy improves local control in rectal cancer treatment, but there are few reports on the influence of radiotherapy on anorectal function. The aim of the present study was to assess late effects of short-course, high-dose radiotherapy on anorectal function after low anterior resection for rectal cancer. Methods Sixty-four patients, randomized within the Stockholm Radiotherapy Trials and operated on with low anterior resection with or without preoperative radiotherapy (mean, 14 years), previously were followed up with quality-of-life questionnaires, clinical examination, anorectal manometry, and endoanal ultrasound. Twenty-one patients had received preoperative radiotherapy of the rectum and 43 patients had been treated with surgery alone. Results Impaired anorectal function was common after low anterior resection for rectal cancer and the risk was increased after radiotherapy. Irradiated patients had significantly more symptoms of fecal incontinence (57 vs. 26 percent, P = 0.01), soiling (38 vs. 16 percent, P = 0.04), and significantly more bowel movements per week (20 vs. 10, P = 0.02). At anorectal manometry, irradiated patients had significantly lower resting (35 mmHg vs. 62 mmHg, P < 0,001) and squeeze pressures (104 mmHg vs. 143 mmHg, P = 0.05). At endoanal ultrasound, irradiated patients had significantly more scarring of the anal sphincters (33 vs. 13 percent, P = 0.03). There were no significant differences in quality-of-life scores between irradiated and nonirradiated patients; however, patients with anal incontinence had significantly lower quality-of-life scores compared to continent patients. Conclusions Short-course radiotherapy, including the anal sphincters, impairs anorectal function and increases gastrointestinal symptoms permanently when the anal sphincters are irradiated. Supported by the The Swedish Cancer Society and the Stockholm Cancer Society. Study was conducted at the Karolinska and Danderyd Hospitals, Stockholm, Sweden. Presented at the Tripartite Colorectal Meeting, Dublin, Ireland, July 3 to 7, 2005. Reprints are not available.     

Physiologic Changes of the Anorectum After Pelvic Radiotherapy for the Treatment of Prostate and Bladder Cancer

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

A prospective randomized placebo-controlled double-blinded pilot study of misoprostol rectal suppositories in the prevention of acute and chronic radiation proctitis symptoms in prostate cancer patients

OBJECTIVE: Radiation proctitis is a known complication of radiation therapy for prostate cancer. Available medical treatment is usually ineffective and has focused on relieving symptoms after damage has occurred. Our study aimed at evaluating the use of misoprostol rectal suppositories in the prevention of acute as well as chronic radiation proctitis symptoms. METHODS: A prospective, randomized, placebo-controlled, double-blinded trial was conducted in patients with recently diagnosed stages B and C prostate cancer who underwent external beam irradiation. Patients received either a misoprostol or a placebo suppository 1 h before each radiation session. Misoprostol suppositories were made from two 200-microg tablets (Cytotec, Searle Pharmaceuticals, Skokie, IL), whereas the placebo was made from cocoa butter. A 12-point radiation proctitis symptom score was obtained from each patient at 4, 8, 12, and 36 wk after radiation therapy. RESULTS: A total of 16 patients were enrolled. Seven patients received placebo, and nine patients received misoprostol. Mean radiation proctitis symptom scores in the placebo group were 4.86, 5.86, 5.71, and 3.83 at 4, 8, 12, and 36 wk, respectively. The mean scores in the misoprostol group were 0.78, 0.67, 0.33, and 0.37 at 4, 8, 12, and 36 wk, respectively. The difference between the two groups was statistically significant (p < 0.05) at 4, 8, 12, and 36 wk. CONCLUSION: Misoprostol rectal suppositories significantly reduce acute and chronic radiation proctitis symptoms in patients receiving radiation therapy for prostate cancer.     

Effects of adjuvant radiotherapy on bowel function and anorectal physiology after low anterior resection for rectal cancer

We compared bowel function and anorectal physiology testing in rectal cancer patients who had undergone surgery alone, i.e. low anterior resection with colonic pouch (SA), to those also having preoperative radiotherapy (PREOP) or postoperative radiotherapy (POSTOP). The PREOP group were recruited from those who received 50.4 Gy (28 daily fractions over 5 1/2 weeks), and had their ileostomies closed for at least 1 year. Equivalent gender- and age-matched SA and POSTOP (50.4–54 Gy) patients who were operated upon during the similar time period were recruited. Bowel function questionnaire, anorectal manometry, anal electrosensation, pudendal nerve motor terminal latencies, barostat rectal sensation measurements and endoanal ultrasound were performed. There were 6 patients in each group. Bowel function questioning revealed that PREOP had significantly more incontinent episodes than SA patients (SA 2.9 ± 1.3, PREOP 10.3 ± 3.4, POSTOP 3.8 ± 0.6 episodes per week: p < 0.05; values expressed as mean ± SEM). The rectal volume of initial distension sensation on barostat ramp program testing was more impaired in the POSTOP than in PREOP group (SA 27.4 ± 5.3, PREOP 17.8 ± 4.3, POSTOP 37.5 ± 6.8 ml; p < 0.05). The left pudendal nerve motor terminal latency was more prolonged in the POSTOP than in the SA patients (SA 1.9 ± 0.2, PREOP 2.3 ± 0.1, POSTOP 4.3 ± 0.7 ms; p < 0.05). Patients who had preoperative radiotherapy had more incontinent episodes, and the rectal sensation may be more impaired after postoperative radiotherapy. Received: 30 December 1999 / Accepted: 17 January 2000     

Long-Term Anorectal Dysfunction After Postoperative Radiotherapy for Rectal Cancer

PURPOSE Adjuvant radiotherapy in the treatment of rectal cancer has been shown to increase long-term morbidity causing severe anorectal dysfunction with physiologic changes whose interaction remains poorly understood. This study examines long-term anorectal morbidity from adjuvant postoperative radiotherapy.METHODS In a prospective study, patients with Dukes B or C rectal carcinoma were randomized to postoperative radiotherapy or no adjuvant treatment after anterior resection. The long-term effect of radiotherapy on anorectal function in a subset of surviving patients was assessed from a questionnaire on subjective symptoms and from physiology laboratory evaluation and flexible sigmoidoscopy.RESULTS Twelve of 15 patients (80 percent) treated with radiotherapy had increased bowel frequency compared with 3 of the 13 patients (23 percent) who did not have radiation therapy (P = 0.003). The former group had loose or liquid stool more often (60 vs. 23 percent, P = 0.05), had fecal incontinence more often (60 vs. 8 percent, P = 0.004), and wore pad more often (47 vs. 0 percent, P = 0.004). They also experienced fecal urgency and were unable to differentiate stool from gas more often. Endoscopy revealed a pale and atrophied mucosa and telangiectasias in the irradiated patients. Anorectal physiology showed a reduced rectal capacity (146 vs. 215 ml, P = 0.03) and maximum squeeze pressure (59 vs. 93 cm H₂O, P = 0.003) in the radiotherapy group. Impedance planimetry demonstrated a reduced rectal distensibility in these patients (P < 0.0001).CONCLUSIONS Adjuvant postoperative radiotherapy after anterior resection causes severe long-term anorectal dysfunction, which is mainly the result of a weakened, less sensitive anal sphincter and an undistensible rectum with reduced capacity.     

Chronic effects of pelvic radiation therapy on anorectal function

PURPOSE: The long-term effect of 4,500 cGy of preoperative radiation on anorectal function has not been prospectively evaluated. METHODS: Anal manometry was performed on 20 patients with rectal carcinoma before and four weeks after receiving 4,500 cGy of external radiotherapy. Four patients underwent proctectomies, three died, and three refused follow-up. Ten patients were available for long-term follow-up and underwent anal manometry at 14 to 42 (average, 35.5) months after initial radiotherapy. RESULTS: No significant difference in mean maximum squeeze or resting pressures was found after radiation therapy. The sphincter profile and minimum sensory threshold were unchanged. The rectoanal inhibitory reflex was present in all patients. Nine patients reported normal anal function. One patient who was incontinent before treatment remained incontinent. CONCLUSION: Preoperative radiation therapy has a minimal chronic effect on anorectal function. Incontinence after sphincter-saving operations for rectal cancer should not be attributed to preoperative radiation therapy.     

Evaluation of preoperative and postoperative radiotherapy on long-term functional results of straight coloanal anastomosis

PURPOSE: Preoperative radiotherapy for rectal cancer avoids radiation to the reconstructed rectum and may circumvent the detrimental effects on bowel function associated with postoperative radiotherapy. We compared the long-term functional results of patients who received preoperative radiotherapy, postoperative radiotherapy, or no radiotherapy in conjunction with low anterior resection and coloanal anastomosis to assess the impact of pelvic radiation on anorectal function. METHODS: One hundred nine patients treated by low anterior resection and straight coloanal anastomosis for rectal cancer between 1986 and 1997 were assessed with a standardized questionnaire at two to eight years after resection. All radiotherapy was given to a total dose of 4,500 to 5,400 cGy with conventional doses and techniques. Most patients received concurrent 5-fluorouracil–based chemotherapy. RESULTS: There were 39 patients in the preoperative radiotherapy group, 11 patients in the postoperative radiotherapy group, and 59 patients in the no radiotherapy group. The postoperative radiotherapy group reported a significantly greater number of bowel movements per 24-hour period (P < 0.01) and significantly more episodes of clustered bowel movements (P < 0.02) than either the preoperative radiotherapy group or the no radiotherapy group. No significant difference in anal continence or satisfaction with bowel function was found among the three groups. CONCLUSION: In this study of straight (nonreservoir) coloanal anastomoses, postoperative pelvic radiotherapy had significant adverse effects on anorectal function, with higher rates of clustering and frequency of defecation than with preoperative radiotherapy. No differences in continence rates were demonstrated, perhaps because of the sample size of the compared groups. We attribute the adverse effects of postoperative radiotherapy to irradiation of the neorectum, which is spared when treatment is given preoperatively. The deleterious effects of adjuvant radiation on long-term anorectal function can be reduced by preoperative treatment.     

Clinical and manometric effects of combined external beam irradiation and brachytherapy for anal cancer

This study evaluates anorectal function after combined tele- and brachytherapy for anal cancer using manometric measurements and a standardized questionnaire. Eight patients received 44±3 Gy external beam radiation followed by 20±4 Gy interstitial brachytherapy with iridium-192. Patients were examined 43 months (range 25–83) after therapy. Maximum anal basal pressure, squeeze pressure, and squeeze increment were significantly lower in patients (50, 163, 115 mmHg, respectively) than in control subjects (75, 285, 180 mmHg, respectively). Decreased anal elasticity was not observed. Anal prestretch “normalized” the contractility of the internal and external sphincter. Thus damage to the anal epithelium and hemorrhoidal cushions seems to be the most important mechanism explaining reduced anal closing pressure values. The rectoanal inhibitory reflex was observed in all but one patient. Rectal compliance was significantly reduced. Whereas all patients could retain a water filled rectal balloon until the maximum tolerable sensation level was reached, the rectal saline infusion test was strongly abnormal. Four patients were perfectly continent. Four patients were incontinent for gas and presented urgency in case of liquid stools with limited soiling occurring once weekly or less; three of them also had urgency for solids. Defecation frequency was increased but regular in most patients. Reduced anal closure together with reduced rectal compliance are at the basis of stool frequency, urgency and partial incontinence with occasional soiling. However, enough reserve sphincter function was maintained to preserve a clinically acceptable degree of anal continence in our patients. Accepted: 21 November 1997     

Proktitis aus Sicht der Proktologie*

Proctitis may cause anal bleeding, anal mucus secretion, diarrhea, urge incontinence, pain at defecation, etc. At digital rectal examination a thickened mucosal lining may be palpated and blood is found on the examination glove. At endoscopy erosive or ulcerative lesions are found that bleed easily on contact. Also polyp-like or even tumor-like lesions, telangiectasias and atypical fistulas can be seen. The symptoms and the findings on examination are quite often unspecific; a detailed history of the patient is most important in the work-up for the differential diagnosis. Serological and microbiological examinations should be done as well as biopsies (except for radiation proctitis). Proctitis may occur after applying external agents that cause chemical, thermal as well as pharmaceutical reactions in the rectum. Proctitis may occur after fecal diversion. Ischemic proctitis causes severe pain and fecal incontinence and may occur postoperatively, after shock/anaphylaxis, etc. The solitary rectal ulcer (syndrome) has a more or less mechanical etiology and shows clearly defined pathohistological lesions. It often occurs in women with outlet obstruction and/or rectal, mucosal or hemorrhoidal prolapse. Except for rectal prolapse, treatment of the solitary rectal ulcer is not always simple or successful. The same applies to radiation proctitis that may occur after radiotherapy. Radiated anorectal tissue regenerates slowly or not at all. Therefore invasive procedures should not be performed because of the high risk for the development of ulceration or fistula. Treatment of radiation proctitis is not always simple and it does not have a high level of evidence. In most cases therapy should be performed individually, according to the severity of complaints.     

Anorectal dysfunction increases with time following radiation therapy for carcinoma of the prostate

OBJECTIVES: To characterize the prevalence and pathophysiology of anorectal dysfunction up to 2 yr following radiation therapy (RT) for localized carcinoma of the prostate. METHODS: Thirty-eight patients, median age 68 (range 60-82) yr with localized prostate carcinoma randomly assigned to one of two radiation dose schedules, underwent evaluation of the following variables of anorectal function before RT, as well as 4-6 wk and 1 and 2 yr after its completion: (1) symptoms, (2) anorectal motility, (3) anorectal sensory function, and (4) anal sphincteric morphology. RESULTS: There was a persistent increase in anorectal symptoms after RT. At 2 yr, bowel frequency, urgency, and fecal incontinence were increased in 50%, 47%, and 26% of patients, respectively. After RT, there were progressive reductions of (1) basal anal pressures, (2) anal pressures in response to squeeze and increased intra-abdominal pressure, (3) rectal compliance, and (4) rectal volumes associated with sensory perception and the desire to defecate. The thickness of the external anal sphincter increased with time after RT. No difference was observed between the patients in the two radiation dose schedules. CONCLUSIONS: Anorectal dysfunction following RT for prostate carcinoma is an underestimated cause of morbidity, which progresses with time. The prevalence and pathophysiology of anorectal dysfunction is similar after treatment with two commonly used radiation dose schedules.     

Function of the anal sphincters after chronic radiation injury.

Anorectal manometry was done in 10 men with chronic radiation proctitis and symptoms of urgency, frequency, and occasional incontinence of faeces. They were compared with 10 asymptomatic age and sex-matched controls. The maximum resting anal canal pressure and the physiological sphincter length were significantly lower (p less than 0.01) in the irradiated group. The rectosphincteric reflex was absent in one patient and showed abnormalities of recovery in four others, who had received radiotherapy. The squeeze pressure of the external sphincter was not significantly different. These results indicate that dysfunction of the internal anal sphincter may contribute to patients' anorectal symptoms after pelvic radiotherapy. Histological evidence suggests that damage to the myenteric plexus is mainly responsible. The manometric function of the external sphincter remains relatively unaffected.     

A simple and effective treatment for hemorrhagic radiation proctitis using formalin

Radiation proctitis is a common complication of radiotherapy for pelvic malignancy. In the more severe form, it leads to intractable or massive hemorrhage, which may require repeated hospital admissions and blood transfusions. Medical therapy in patients with radiation proctitis is usually ineffective, whereas surgery is associated with a high morbidity and mortality. Eight patients (seven females and one male) with hemorrhagic radiation proctitis were Treated over a six-month period with endoluminal formalin. The technique used ensured minimal contact with formalin. The median age of the patients was 68 years (range, 42–73 years). Seven patients had had cancer of the uterine cervix, and one patient had had cancer of the prostate treated with radiotherapy at a median time of 30 months (range, 9–46 months) previously. The median duration of time of symptomatic rectal hemorrhage before formalin therapy was eight months (range, 1–12 months). The median number of units of blood transfused previously per patient was four (range, 2–32). The time taken for formalin therapy was 20 minutes (range, 10–70 minutes). One patient required repeat formalin application at two weeks. Bleeding ceased immediately in seven patients after formalin treatment. No further bleeding was noted, nor was any blood transfusion needed, at follow-up at four months (range, 1–6 months). Formalin therapy is a simple, inexpensive, and effective treatment for hemorrhagic radiation proctitis.     

Three-dimensional conformal radiotherapy combined with FOLFOX4 chemotherapy for unresectable recurrent rectal cancer

AIM: To investigate the effect of three-dimensional conformal radiotherapy (3-DCRT) in combination with FOLFOX4 chemotherapy for unresectable recurrent rectal cancer. METHODS: Forty-eight patients with unresectable recurrent rectal cancer were randomized and treated by 3-DCRT or 3-DCRT combined with FOLFOX4 chemotherapy between September 2001 and October 2003. For the patients without prior radiation history, the initial radiation was given to the whole pelvis by traditional methods with tumor dose of 40 Gy, followed by 3-DCRT for the recurrent lesions to the median total cumulative tumor dose of 60 Gy (range 56-66 Gy); for the post-radiation recurrent patients, 3-DCRT was directly given for the recurrent lesions to the median tumor dose of 40 Gy (36-46 Gy). For patients in the study group, two cycles chemotherapy with FOLFOX4 regimen were given concurrently with radiotherapy, with the first cycle given simultaneously with the initiation of radiation and the second cycle given in the fifth week for patients receiving conventional pelvis radiation or given in the last week of 3-DCRT for patients receiving 3-DCRT directly. Another 2-4 cycles (average 3.6 cycles) sequential FOLFOX4 regimen chemotherapy were given to the patients in the study group, beginning at 2-3 wk after chemoradiation. The outcomes of symptoms relieve, tumor response, survival and toxicity were recorded and compared between the study group and the control group. RESULTS: For the study group and the control group, the pain-alleviation rates were 95.2% and 91.3% (P>0.05); the overall response rates were 56.5% and 40.0% (P>0.05); the 1-year and 2-year survival rates were 86.9%, 50.2% and 80.0%, 23.9%, with median survival time of 25 mo and 16 mo (P<0.05); the 2-year distant metastasis rates were 39.1% and 56.0% (P=0.054), respectively. The side effects, except peripheral neuropathy which was relatively severer in the study group, were similar in the the two groups and well tolerated. CONCLUSION: Three-dimensional conformal radiotherapy combined with FOLFOX4 chemotherapy for unresectable recurrent rectal cancer is a feasible and effective therapeutic approach, and can reduce distant metastasis rate and improve the survival rate.     

Effective use of argon plasma coagulation in the treatment of severe radiation proctitis

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.Presented in abstract form at the meeting of the American Gastroenterological Association, San Diego, California, May 21 to 24, 2000.     

Early effect of external beam radiation therapy on the anal sphincter: A study using anal manometry and transrectal ultrasound

The early effect of pelvic irradiation on the anal sphincter has not been previously investigated. This study prospectively evaluated the acute effect of preoperative radiation on anal function. Twenty patients with rectal carcinoma received 4,500 cGy of preoperative external beam radiation. The field of radiation included the sphincter in 10 patients and was delivered above the anorectal ring in 10 patients. Anal manometry and transrectal ultrasound were performed before and four weeks after radiotherapy. No significant difference in mean maximal squeeze or resting pressure was found after radiation therapy. An increase in mean minimal sensory threshold was significant. Histologic examination revealed minimal radiation changes at the distal margin in 8 of 10 patients who underwent low anterior resection and in 1 of 3 patients who underwent abdominoperineal resection. We conclude that preoperative radiation therapy has minimal immediate effect on the anal sphincter and is not a major contributing factor to postoperative incontinence in patients after sphincter-saving operations for rectal cancer.Read at the meeting of The American Society of Colon and Rectal Surgeons, Boston, Massachusetts, May 12 to 17, 1991. Winner of the Northwest Society of Colon and Rectal Surgeons Award.