Efficacy of hyperbaric oxygen therapy in patients with radiation‐induced rectal ulcers: Report of five cases

For decades, hyperbaric oxygen therapy has been considered a treatment option in patients with chronic radiation‐induced proctitis after pelvic radiation therapy. Refractory cases of chronic radiation‐induced proctitis include ulceration, stenosis, and intestinal fistulas with perforation. Appropriate treatment needs to be given. In the present study, we assessed the efficacy of hyperbaric oxygen therapy in five patients with radiation‐induced rectal ulcers. Significant improvement and complete ulcer resolution were observed in all treated patients; no side‐effects were reported. Hyperbaric oxygen therapy has a low toxicity profile and appears to be highly effective in patients with radiation‐induced rectal ulcers. However, hyperbaric oxygen therapy alone failed to improve telangiectasia and easy bleeding in four of the five patients; these patients were further treated with argon plasma coagulation (APC). Although hyperbaric oxygen therapy may be effective in healing patients with ulcers, it seems inadequate in cases with easy bleeding. Altogether, these data suggest that combination therapy with hyperbaric oxygen therapy and APC may be an effective and safe treatment strategy in patients with radiation‐induced rectal ulcers.     

Radiation-induced rectal ulcer--prognostic factors and medical treatment

BACKGROUND/AIMS: We conducted this study in order to investigate prognostic factors, and the difference of efficacy of three medical regimens, in the treatment of radiation-induced rectal ulcer. METHODOLOGY: We enrolled 38 pts, with different ages, the free interval from radiation to the appearance of symptoms, and the rectal ulcer size. Medical regimens were 1) sucralfate enema, 2) salasopyrine + hydrocortisone enemas, 3) combination of regimens. We analyzed the difference of frequency of ulcer healing and the time necessary for ulcer healing, between the patients in the different groups. RESULTS: The patients with late appearance of symptoms had significantly shorter time to ulcer healing than the patients with early appearance of symptoms (p=0.032). The patients who received sucralfate alone significantly more frequently achieved ulcer healing, than the patients with salasopyrine and hydrocortisone (p=0.046), and combination regimen (p=0.003). The patients with sucralfate (p=0.009), and with salasopyrine + hydrocortisone (p=0.0387), demanded significantly shorter time to ulcer healing than the patients who received combination treatment. CONCLUSIONS: The free interval may be an important prognostic factor, in patients with rectal ulcer concerning treatment duration. It seems that treatment with sucralfate alone may be the treatment of choice, for patients with radiation-induced rectal ulcer.     

Quality of healing of gastric ulcers: Natural products beyond acid suppression简

Gastric ulcer is a chronic disease featured with unexpected complications, including bleeding, stenosis and perforation, as well as a high incidence of recurrence. Clinical treatments for gastric ulcer have allowed the rapid development of potent anti-ulcer drugs during the last several decades. Gastric ulcer healing is successful with conventional treatments including H₂-receptor antagonists, and proton pump inhibitors (PPIs) have been essential for ulcer healing and prevention of complications. Additionally, Helicobacter pylori eradication therapy is effective in reducing ulcer recurrence and leads to physiological changes in the gastric mucosa which affect the ulcer healing process. However, in spite of these advancements, some patients have suffered from recurrence or intractability in spite of continuous anti-ulcer therapy. A new concept of the quality of ulcer healing (QOUH) was initiated that considers the reconstruction of the mucosal structure and its function for preventing ulcer recurrence. Although several gastroprotection provided these achievements of the QOUH, which PPI or other acid suppressants did not accomplish, we found that gastroprotection that originated from natural products, such as a newer formulation from either Artemisia or S-allyl cysteine from garlic, were very effective in the QOUH, as well as improving clinical symptoms with fewer side effects. In this review, we will introduce the importance of the QOUH in ulcer healing and the achievements from natural products.     

Ecabet sodium promotes the healing of trinitrobenzene‐sulfonic‐acid‐induced ulceration by enhanced restitution of intestinal epithelial cells

Background and Aims: Ecabet sodium (ES) is a gastric mucosal protective and ulcer‐healing agent. Recently enema therapy with ES was found to be effective for the treatment of human ulcerative colitis as well as experimental colitis in an animal model. Whereas ES possesses potential as a novel treatment for ulcerative colitis, its precise mechanism of action remains to be elucidated. In this study, we investigated the therapeutic efficacy of ES in an experimental rat model of colitis, and evaluated the restitution of intestinal epithelial cells treated with ES in vitro. Methods: Acute colitis was induced with trinitrobenzene sulfonic acid (TNBS) in male Wistar rats. Rats received intrarectal treatment with ES daily starting on day 7 and were sacrificed on day 14 after the administration of TNBS. The distal colon was removed to evaluate various parameters of inflammation. Moreover, wound‐healing assays were used to determine the enhanced restitution of rat intestinal epithelial (RIE) cells treated with ES. Results: Intracolonic administration of ES accelerated TNBS‐induced ulcer healing. Increases in the wet weight of the colon after TNBS administration were significantly inhibited by ES treatment. The wound assay revealed ES enhancement of the migration of RIE cells migration through the phosphorylation of extracellular signal‐regulated kinase. Conclusion: Daily administration of an ES enema promoted the healing of intestinal mucosal injury, in part by the enhanced restitution of intestinal epithelial cells via extracellular signal‐regulated kinase activation. ES may thus represent a novel therapeutic approach for the treatment of inflammatory bowel disease.     

Risk Factors For Duodenal Ulcer Recurrence: Three-year Follow-up during Famotidine Maintenance Therapy

The recurrence-free rate and factors related to recurrence after healing were investigated in duodenal ulcer patients on H₂-blocker maintenance therapy with famotidine. Famotidine maintenance therapy (20 or 40 mg once a day before bedtime) was performed in 488 evaluable patients after endoscopically-proven healing of ulcers (S₁ or S₂). The cumulative recurrence-free rates were 81.1%, 65.1% and 58.2%, respectively, after one, two and three years of maintenance therapy. Among various background factors, those which have been suggested to be closely associated with ulcer recurrence were compared on the basis of their relation to the recurrence-free rate. These factors included a past history of duodenal ulcer, smoking, alcohol use, bulbar deformation, the endoscopic stage of ulcer healing, concomitant drugs and compliance with famotidine therapy. Recurrence correlated most significantly with a past history of duodenal ulcer and with compliance. Compliance was categorized as excellent, good, fair or poor. The recurrence-free rate was significantly lower in patients with excellent compliance than in any other compliance group. A famotidine dose of 40 mg/day (the standard dose), versus the half dose of 20 mg/day, produced no significant difference in the cumulative recurrence-free rate and it was therefore suggested that 20 mg/day of famotidine is comparable to 40 mg/day in its preventive effect on duodenal ulcer recurrence. In addition, because recurrence was more common in patients who had previously experienced recurrence, a past history of ulcer was suggested to be a significant risk factor for ulcer recurrence.     

Prognosis of the infected diabetic foot ulcer: a 12‐month prospective observational study

Aims

To determine clinical outcomes and explore prognostic factors related to ulcer healing in people with a clinically infected diabetic foot ulcer.

Methods

This multicentre, prospective, observational study reviewed participants’ data at 12 months after culture of a diabetic foot ulcer requiring antibiotic therapy. From participants’ notes, we obtained information on the incidence of wound healing, ulcer recurrence, lower extremity amputation, lower extremity revascularization and death. We estimated the cumulative incidence of healing at 6 and 12 months, adjusted for lower extremity amputation and death using a competing risk analysis, and explored the relationship between baseline factors and healing incidence.

Results

In the first year after culture of the index ulcer, 45/299 participants (15.1%) had died. The ulcer had healed in 136 participants (45.5%), but recurred in 13 (9.6%). An ipsilateral lower extremity amputation was recorded in 52 (17.4%) and revascularization surgery in 18 participants (6.0%). Participants with an ulcer present for ~2 months or more had a lower incidence of healing (hazard ratio 0.55, 95% CI 0.39 to 0.77), as did those with a PEDIS (perfusion, extent, depth, infection, sensation) perfusion grade of ≥2 (hazard ratio 0.37, 95% CI 0.25 to 0.55). Participants with a single ulcer on their index foot had a higher incidence of healing than those with multiple ulcers (hazard ratio 1.90, 95% CI 1.18 to 3.06).

Conclusions

Clinical outcomes at 12 months for people with an infected diabetic foot ulcer are generally poor. Our data confirm the adverse prognostic effect of limb ischaemia, longer ulcer duration and the presence of multiple ulcers.     

Clinical experience with local excision and postoperative radiation therapy for rectal cancer

The standard surgical treatment for patients with potentially curable transmural and/or node-positive rectal cancer is a low anterior resection or abdominoperineal resection. There is increasing interest in the use of local excision and postoperative radiation therapy as primary therapy for selected rectal cancers. The limited data suggest that the approach of local excision and postoperative radiation therapy should be limited to patients with either T ₁ tumors with adverse pathologic factors or T₂ tumors. Transmural tumors have a 24 percent local failure rate and are treated more effectively with standard surgery and preoperative or postoperative therapy. The results of local excision and postoperative radiation therapy are encouraging; however, more experience is needed to determine whether this approach ultimately has local control and survival rates similar to standard surgery.     

Stapled Transanal Rectal Resection in Solitary Rectal Ulcer Associated with Prolapse of the Rectum: A Prospective Study

Purpose At present, none of the conventional surgical treatments of solitary rectal ulcer associated with internal rectal prolapse seems to be satisfactory because of the high incidence of recurrence. The stapled transanal rectal resection has been demonstrated to successfully cure patients with internal rectal prolapse associated with rectocele, or prolapsed hemorrhoids. This prospective study was designed to evaluate the short-term and long-term results of stapled transanal rectal resection in patients affected by solitary rectal ulcer associated with internal rectal prolapse and nonresponders to biofeedback therapy. Methods Fourteen patients were selected on the basis of validated constipation and continence scorings, clinical examination, anorectal manometry, defecography, and colonoscopy and were submitted to biofeedback therapy. Ten nonresponders were operated on and followed up with incidence of failure, defined as no improvement of symptoms and/or recurrence of rectal ulceration, as the primary outcome measure. Operative time, hospital stay, postoperative pain, time to return to normal activity, overall patient satisfaction index, and presence of residual rectal prolapse also were evaluated. Results At a mean follow-up of 27.2 (range, 24–34) months, symptoms significantly improved, with 80 percent of excellent/good results and none of the ten operated patients showed a recurrence of rectal ulcer. Operative time, hospital stay, and time to return to normal activity were similar to those reported after stapled transanal rectal resection for obstructed defecation, whereas postoperative pain was slightly higher. One patient complained of perineal abscess, requiring surgery. Discussion The stapled transanal rectal resection is safe and effective in the cure of solitary rectal ulcer associated with internal rectal prolapse, with minimal complications and no recurrences after two years. Randomized trials with sufficient number of patients are necessary to compare the efficacy of stapled transanal rectal resection with the traditional surgical treatments of this rare condition.     

Primary Perineal Wound Closure After Preoperative Radiotherapy and Abdominoperineal Resection has a High Incidence of Wound Failure

PURPOSE Neoadjuvant radiation therapy has been used increasingly to downstage rectal cancer and decrease local recurrence. Despite its efficacy, preoperative radiation therapy may inhibit healing and contribute to wound complications. This study was designed to evaluate perineal wound complications after abdominoperineal resection.METHODS The clinical records of a consecutive series of patients who underwent abdominoperineal resection for rectal carcinoma between 1988 and 2002 were reviewed. Demographic data, disease stage, and use of preoperative radiation therapy were recorded. Major wound complications included delayed wound healing (>1 month), wound infection requiring drainage/debridement, or reoperation.RESULTS A total of 160 patients underwent abdominoperineal resection with primary closure of the perineal wound (mean age, 63 ± 12 years); 117 (73 percent) patients received preoperative radiation therapy; 114 received radiation therapy for rectal cancer (radiation therapy + chemotherapy = 107, radiation therapy alone = 7); 3 received radiation therapy for other pelvic malignancies. Median radiation dose was 5,040 (range, 900–5,400) cGY. Overall wound complication rate was 41 percent. Major wound complication rate was 35 percent. Delayed healing was the most common complication (24 percent), followed by infection (10 percent). Radiation therapy increased the risk of any wound complication (47 vs. 23 percent; P = 0.005), risk of a major wound complication (41 vs. 19 percent; P = 0.021), and risk of infection (14 vs. 0 percent; P = 0.015). Risk of wound complications did not correlate with age, gender, disease stage, smoking, or diabetes.CONCLUSIONS Wound complications are frequent after abdominoperineal resection and primary closure of the perineum. Preoperative radiation therapy doubles the rate of total and major perineal wound complications. Alternatives to primary perineal closure should be considered, particularly after radiation therapy.Read at meeting of The American Society of Colon and Rectal Surgeons, Dallas, Texas, May 8 to 13, 2004.     

Successful treatment of a benign solitary rectal ulcer by temporary diverting sigmoidostomy: Report of a case

Summary A rare case of a solitary benign rectal ulcer in which conservative medical therapy was unsuccessful is described. Diversion of the fecal stream by temporary sigmoidostomy resulted in rapid healing of the ulcer. This entity presents diagnostic and therapeutic problems, which are discussed. The use of temporary sigmoidostomy in such cases is recommended. Department of Surgery Department of Gastroenterology     

Efficacy of ecabet sodium enema on intractable rectal ulcer after piecemeal endoscopic mucosal resection for rectal tumor

We describe a case with rectal bleeding from a rectal ulcer after endoscopic mucosal resection (EMR), successfully treated with an ecabet sodium (ES) enema. A 44-year-old woman with a laterally spreading rectal tumor of a granular type, 60 mm in diameter, underwent piecemeal EMR. After the EMR, she suffered from rectal bleeding on several occasions over a period of 1 month. Although she was repeatedly treated with thermocoagulation by a heater probe to stop the bleeding, a rectal ulcer with visible vessels still remained at the resected site. Because the rectal ulcer was considered to be intractable, an ES enema was used twice a day (1.5 g) for 2 weeks, which improved rectal bleeding. Colonoscopic findings revealed that the ulcer improved with mucosal healing after the ES enema treatment. This represents the first report of an ES enema treatment in a patient with a rectal ulcer after EMR. Further studies are needed to determine the effectiveness and safety of using an ES enema in patients with EMR-related refractory colorectal ulcers.     

Candida albicans infection of gastric ulcer frequency and correlation with medical treatment

This paper reports the results of a multicenter prospective study of 188 consecutive patients affected by gastric ulcer, verified by endoscopy, in whom the frequency of a mycotic infection of the lesion was evaluated as well as the eventual influence of such pathology on the efficiency of medical treatment, the healing rate, and the healing time. A mycotic infection, defined as penetration of the periulcerous mucosa by the fungi, was found in only 13 patients (6.9%). No significant differences were found in the healing rate and helaing time among these patients treated with H₂-receptor antagonists and a control group of 43 matched gastric ulcer patients treated in the same period with the same therapy. It would appear from the data that mycotic infections of the gastric ulcer do not modify the efficiency of medical treatment.     

Healing of chronic gastroduodenal ulcerations by antacids

Antacids show gastroprotective action against various irritants in experimental animals and enhance the healing of chronic gastroduodenal ulcers in humans but the mechanisms of these effects are unknown. The present study was designed to determine whether prostaglandin (PG) and epidermal growth factor (EGF), which also have protective and antiulcer properties, contribute to the action of antacids on rat's stomach. It was found that Maalox 70 and its active component, Al(OH)₃, enhance significantly the healing of chronic gastric and duodenal ulcers observed during 7 and 14 days after their induction. Pretreatment with indomethacin caused a significant prolongation of ulcer healing, and this was accompanied by a significant reduction in PG and EGF formation, suggesting that both factors may be involved in ulcer healing. Maalox and Al(OH)₃ failed to prevent the suppression of PG by indomethacin but were equally effective in ulcer healing in rats without and with indomethacin administration, suggesting that endogenous PG may not play any important role in the healing process by these drugs. Removal of salivary glands, the major source of EGF, also prolonged ulcer healing but, again, Maalox was as effective in ulcer healing as in rats with intact salivary glands. Our findings that Maalox at pH above 3.0 binds significant amounts of EGF, enhances the binding of EGF to the ulcer area, and stimulates mucosal growth, suggest that EGF may be involved in ulcer healing; however, because antacids are also effective after sialoadenectomy, EGF does not seem to be the major factor in ulcer healing by these drugs.     

Endoscopic Ultrasonographic Evaluation of Gastric Ulcer Healing on Treatment with Proton Pump Inhibitors versus H2-Receptor Antagonists

Tanaka M, Maruoka A. Chijiiwa Y, Tanaka M, Nawata H. Endoscopic ultrasonographic evaluation of gastric ulcer healing on treatment with proton pump inhibitors versus H₂-receptor antagonists. Scand J Gastroenterol 1994;29:1140-1144.

Background: It has been reported that time to peptic ulcer healing is shorter with proton pump inhibitors (PPI) than with H₂-receptor antagonists (H₂-RA). This study was designed to examine the difference in the healing process between gastric ulcers treated with PPI and those treated with H₂-RA.

Methods: The healing of deep gastric ulcers treated with PPI (n = 11) or H₂-RA (n = 13) was evaluated with endoscopic ultrasonography (EUS). Every 2 weeks during treatment EUS variables such as the width and the depth of the ulcer crater, the thickness and size of the low echoic area of the ulcer base, and the distance of the disrupted muscularis propria were measured. The contraction rates of EUS variables, the ratios of the contraction rate of the depth to that of the width of the ulcer crater (D/W ratio) and the contraction rate of the distance of the disrupted muscularis propria layer to that of the width of the ulcer crater (Dm/W ratio) were calculated.

Results: Only at week 2 were the D/W ratio and Dm/W ratio significantly higher in the group receiving PPI (D/W ratio, 1.79 ±0.701; Dm/W ratio, 0.938 ±0.207) than in the group receiving H₂-RA (D/W ratio, 1.10 + 0.559; Dm/W ratio, 0.641 ±0.166).

Conclusion: This study demonstrated that PPI therapy is associated with more rapid and stronger healing than obtained with H₂-RA during the early treatment period.     

Healing of endoscopic biopsy sites in the human rectum

The time required in man for a rectal ulcer created with endoscopic biopsy forceps to heal is unknown. To answer this question, we created a large ulcer (approximately 8 mm in diameter) and a smaller ulcer (approximately 4 mm in diameter) in four healthy young men and followed the healing of the ulcers by visual examination every 4 days. Complete healing of the large ulcer had not occurred on days 4 and 8, while by day 12, three had healed and by day 16, all four had disappeared. Of the small ulcers, two had healed by day 8, and all had healed by day 12. This study suggests that it takes approximately 8-12 days for an artificially created rectal lesion to heal completely.     

Factors Influencing the Relapse of Gastric Ulcers During H2-Receptor Antagonist Maintenance Therapy

Abstract: We performed H₂-receptor antagonist maintenance therapy for 2 years on 146 patients with healed gastric ulcers (including those with concurrent duodenal ulcers), and determined the cumulative endoscopic and symptomatic recurrence rates. We also investigated the factors involved in ulcer recurrence in the first 12 months of maintenance therapy. The cumulative endoscopic non-recurrence rate was 70.0% at 12 months and 57.2% at 24 months, while the cumulative symptomatic non-recurrence rate was 84.8% at 12 months and 75.0% at 24 months. The factors contributing to endoscopic recurrence were the presence of a concomitant disease, the presence of duodenal ulcer, the type of ulcer, and the endoscopic stage at healing. The factors related to symptomatic recurrence were smoking and the type of ulcer. Multivariate analysis showed that the type of ulcer, smoking, and the endoscopic stage at healing influenced the risk of recurrence.     

HEALING OF SOLITARY RECTAL ULCERS WITH MULTIPLE SESSIONS OF ARGON PLASMA COAGULATION

Background: Solitary rectal ulcer syndrome (SRUS) is an uncommon disorder of evacuation. Management of bleeding ulcers is usually unsatisfactory with conventional treatment. Argon plasma coagulation (APC) has been reported to control bleeding; however, it has not been shown to result in ulcer healing. The aim of the present study was to: (i) to investigate the efficacy and safety of APC in controlling bleeding from SRUS; and (ii) to study its efficacy in the healing of ulcer/s. Methods: Twenty‐four patients with bleeding SRUS diagnosed on clinical, colonoscopic, and histological findings were randomized to receive either standard care alone (12 patients) or to undergo multiple sessions of APC in addition (12 patients). All patients were followed up to determine ulcer healing. Results: Twenty‐four patients with a mean duration of symptoms of 12.6 ± 4.8 months were included. Bleeding was controlled with one (n = 5) or two sessions (n = 7) of APC. Reduction in size and depth of ulcer was noted. Eight out of 12 patients who received APC had complete healing of ulcers after four to eight sessions, carried out 2–4 weeks apart. The remaining four patients had a reduction in size and depth of ulcers compared to their pretreatment appearance. All patients were advised to have a high intake of fluids, fiber and laxatives, and to undergo biofeedback and behavior modification therapy in addition to the treatment. Conclusions: APC controls bleeding in patients with SRUS and it also improves the healing of these ulcers.     

Peptic ulcer recurrence during maintenance therapy with H2-receptor antagonist following first-line therapy with proton pump inhibitor

We investigated the peptic ulcer recurrence rates during maintenance therapy with H₂-receptor antagonists (H₂RAs) following first-line therapy with a proton pump inhibitor (PPI). Patients with gastric ulcer (GU) or duodenal ulcer (DU) were enrolled in this study; 583 eligible patients (GU, 325; DU, 258) were administered lansoprazole (30 mg/day for 8 weeks for GU, and the same dosage for 6 weeks for DU) as first-line therapy, and a half dose of H₂RA as maintenance therapy for 12 months. Endoscopic photographs were taken before administration and after 8 (GU) and 6 (DU) weeks of lansoprazole administration. Ulcer stage was evaluated using the classification of Sakita and Miwa. Endoscopic examinations were performed 6 months or 12 months after the start of maintenance therapy or when a recurrence was suspected because of the appearance of subjective symptoms. The healing rates for GU and DU patients after completion of lansoprazole therapy were 79% in both groups, while the S₂-stage healing rates were 18% and 31%, respectively. At 1 year after the start of maintenance therapy, the recurrence rates were 25% for GU and 39% for DU patients. In DU patients, the recurrence rates from S₁-stage and S₂-stage were 49% and 20%, respectively (P = 0.004), but no significant difference was found between these rates in GU patients. The recurrence rates in H. pylori-positive patients before lansoprazole administration were 27% for GU and 43% for DU patients. We concluded that the maintenance therapy with a half-dose of H₂RA following PPI therapy was insufficient to prevent recurrences of GU and DU. Received: February 28, 2000 / Accepted: June 23, 2000     

Prostaglandin E<Subscript>1</Subscript> (Misoprostol) overcomes the adverse effect of chronic cigarette smoking on duodenal ulcer healing

Chronic cigarette smoking adversely affects duodenal ulcer healing despite treatment by potent gastric acid-reducing agents. Prostaglandins of the E series possess antisecretory and cytoprotective properties and theoretically offer advantages over existing therapeutic agents. A double-blind randomized study was performed to compare complete duodenal ulcer healing as assessed by endoscopies every two weeks for up to 12 weeks. Two hundred twenty-nine patients were randomized to receive misoprostol, an orally stable synthetic derivative of prostaglandin E₁, in 200-μg or 300-μg qid dosages, or placebo. Life-table analysis showed that (1) both regimens of misoprostol were significantly more effective than placebo, achieving healing rates of 61% and 71%, respectively, at four weeks, and (2) cigarette smoking significantly impaired healing by placebo but not by misoprostol. In fact, the time-healing curves of smokers and nonsmokers on the higher dose of misoprostol completely overlapped. Furthermore, delayed treatment and large ulcer diameter adversely affected healing by misoprostol in smokers, whereas in nonsmokers, high basal and maximal acid output were unfavorable. Misoprostol is recommended for the treatment of duodenal ulcer, particularly in chronic smokers early in a given period of symptoms.