Development of an Indigo Naturalis Suppository for Topical Induction Therapy in Patients with Ulcerative Colitis.

BACKGROUND: Indigo naturalis (IN) consists of ligands for the aryl hydrocarbon receptor and exhibits anti-inflammatory effects. Previously, we demonstrated that an 8-week treatment with oral IN is effective in inducing a clinical response in patients with ulcerative colitis (UC). Some UC patients with proctitis are refractory to topical mesalamine or corticosteroids and therefore require an alternative topical treatment. OBJECTIVES: We aimed to prospectively evaluate the safety and efficacy of IN suppositories in UC patients. METHOD: We performed an open-label, single-center, prospective pilot study from February 2018 to October 2018. A total of 10 patients with active UC, who had moderate to severe inflammation from the rectum to the sigmoid colon, were enrolled. The patients received a daily dose of 50 mg IN suppository for 4 weeks. The primary endpoint was safety at week 4. RESULTS: Although 1 patient experienced anal pain, no serious adverse events were observed. At week 4, the rates of clinical remission and mucosal healing were 30 and 40%, respectively. Mayo rectal bleeding subscores significantly improved after treatment (1.80 ± 0.13 vs. 0.90 ± 0.28; p = 0.009). Approximately 80% of the patients with a baseline Mayo endoscopic subscore in the rectum (r-MES) of 2 achieved mucosal healing, but those with a baseline r-MES of 3 did not. CONCLUSIONS: We found that 4 weeks of IN suppository can be tolerated by UC patients, but its efficacy was limited by the severity of the disease. Further investigation will be needed in order to confirm the optimum dose of IN suppository for patients with UC.

Is Dyssynergic Defecation an Unrecognized Cause of Chronic Constipation in Patients Using Opioids?

OBJECTIVES: The impact of opioids on anorectal function is poorly understood but potentially relevant to the pathogenesis of opioid-induced constipation (OIC). To evaluate anorectal function testing (AFT) characteristics, symptom burden, and quality of life in chronically constipated patients prescribed an opioid (OIC) in comparison with constipated patients who are not on an opioid (NOIC). METHODS: Retrospective analysis of prospectively collected data on 3,452 (OIC = 588 and NOIC = 2,864) chronically constipated patients (Rome 3) who completed AFT. AFT variables included anal sphincter pressure and response during simulated defecation, balloon expulsion test (BET), and rectal sensation. Dyssynergic defecation (DD) was defined as an inability to relax the anal sphincter during simulated defecation and an abnormal BET. Patients completed Patient Assessment of Constipation Symptoms (PAC-SYM) and Patient Assessment of Constipation Quality of Life (PAC-QOL) questionnaires. RESULTS: The mean age of the study cohort was 49 years. Most patients were women (82%) and whites (83%). Patients with OIC were older than NOIC patients (50.7 vs 48.3, P = 0.001). OIC patients were significantly more likely to have DD (28.6% vs 21.4%, P < 0.001), an abnormal simulated defecation response on anorectal manometry (59% vs 43.8%, P < 0.001), and an abnormal BET (48% vs 42.5%, P = 0.02) than NOIC patients. OIC patients reported more severe constipation symptoms (P < 0.02) and worse quality of life (P < 0.05) than NOIC patients. DISCUSSION: Chronically constipated patients who use opioids are more likely to have DD and more severe constipation symptoms than NOIC.

Acupoint Specificity on Colorectal Hypersensitivity Alleviated by Acupuncture and the Correlation with the Brain-Gut Axis.

This project was focused on the study of the effect of the different acupoints on visceral hypersensitivity and the correlation with the brain-gut axis. By using a mouse model of zymosan-induced colorectal hypersensitivity, and observing the response of hypersensitivity model to colorectal distension stimulation in acupuncture at different acupoints, we selected the specific acupoints. With immunohistochemical staining method, we observed c-fos expression, distribution and changes after acupuncture on sensory pathway, including colorectum, spinal dorsal horn and different regions of brain center in the model with colorectal distension stimulation, and evaluated the acupuncture effect on brain-gut axis. The results revealed that the effectiveness of acupuncture for alleviating visceral hypersensitivity was different at individual acupoint, meaning Tianshu (ST25), Zusanli (ST36) and Shangjuxu (ST37) > Quchi (LI11) and Dachangshu (BL25) > Ciliao (BL32). C-fos expression was concentrated in anterior cingulate cortex, hypothalamus, spinal dorsal horn and colorectum in model of zymosan-induced colorectal hypersensitivity and it was down-regulated after acupuncture. The results demonstrates that the acupoint specificity presents in acupuncture for relieving visceral hypersensitivity and the effects are more predominated at the acupoints on stomach meridian innervated by the same or adjacent spinal ganglion segments. The model of zymosan-induced colorectal hypersensitivity can be the animal model simulating brain-gut interaction.

Management of patients with rectus sheath hematoma: Personal experience.

BACKGROUND/PURPOSE: Rectus sheath hematoma (RSH) is a rare clinical entity. It can be mistaken for other intra-abdominal disorders, which can result in diagnostic and therapeutic difficulties. This study was undertaken to analyze the clinical presentation, diagnostic modalities, and management of patients affected with RSH. METHODS: Between January 2008 and June 2011, eight patients (5 men and 3 women with a mean age of 53 years) with RSH were evaluated according to demographic characteristics, clinical and radiological findings, and methods of treatment. RESULTS: Six patients developed RSH after anticoagulant therapy; one after local trauma, and one after laparoscopic intervention. Six patients were treated nonsurgically; one patient underwent embolization of the inferior epigastric artery and one underwent ligation of the bleeding vessel. The average hospital stay was 6 days. There were no mortality or thromboembolic complications. CONCLUSION: RSH is a rare nonneoplastic entity that is usually associated with abdominal trauma and/or anticoagulant therapy. The gold standard for diagnosis is computed tomography, and ultrasonography can be used in follow-up. The treatment of choice is nonsurgical therapy because RSH is a self-limited condition. Surgical intervention should be reserved for cases with hemodynamic instability.

[Perianal and rectal ulcers due to abuse of paracetamol-codeine suppositories]. / Perianale und rektale Ulzera nach Abusus von Paracetamol-Codein-Suppositorien.

A 61-year-old woman presented with a progressive perianal ulcer which had developed 4 months ago. Upon further examination, another ulcer of the rectum was detected. Anorectal malignancies, viral infections or primary inflammatory bowel disease were not found. It could be demonstrated that the ulcers were induced by paracetamol and codeine suppositories. After discontinuation of these suppositories, the perianal ulcers healed almost completely within 3 weeks. The pathogenesis of paracetamol-induced ulcers is unknown. However, dose-dependent vasoconstriction is a possible explanation.

Postprostatectomy ultrasound-guided transrectal implantation of gold markers for external beam radiotherapy. Technique and complications rate.

BACKGROUND AND PURPOSE: Postprostatectomy radiotherapy (RT) improves survival in adjuvant and salvage settings. The implantation technique and complications rate of gold markers in the prostate bed for high-precision RT were analyzed. PATIENTS AND METHODS: Patients undergoing postprostatectomy RT for prostate-specific antigen (PSA) relapse or high-risk disease were enrolled in the study. Under transrectal ultrasound guidance, three fine gold markers were implanted in the prostate bed and the technical difficulties of insertion were documented. Patients received our self-designed questionnaires concerning complications and pain. The influence of anticoagulants and coumarins on bleeding was analyzed, as was the effect of potential risk factors on pain. RESULTS: In 77 consecutive patients, failure of marker implantation or marker migration was seen in six cases. Rectal bleeding was reported by 10 patients and 1 had voiding complaints. No macroscopic hematuria persisting for more than 3 days was observed. Other complications included rectal discomfort (n = 2), nausea (n = 1), abdominal discomfort (n = 1), and pain requiring analgesics (n = 4). No major complications were reported. On a 0-10 visual analogue scale (VAS), the mean pain score was 3.7. No clinically significant risk factors for complications were identified. CONCLUSION: Transrectal implantation of gold markers in the prostate bed is feasible and safe. Alternatives like cone beam computed tomography (CBCT) should be considered, but the advantages of gold marker implantation for high-precision postprostatectomy RT would seem to outweigh the minor risks involved.

Long-term sensitization of mechanosensitive and -insensitive afferents in mice with persistent colorectal hypersensitivity.

Afferent input contributes significantly to the pain and colorectal hypersensitivity that characterize irritable bowel syndrome. In the present study, we investigated the contributions of mechanically sensitive and mechanically insensitive afferents (MIAs; or silent afferents) to colorectal hypersensitivity. The visceromotor response to colorectal distension (CRD; 15-60 mmHg) was recorded in mice before and for weeks after intracolonic treatment with zymosan or saline. After CRD tests, the distal colorectum with the pelvic nerve attached was removed for single-fiber electrophysiological recordings. Colorectal afferent endings were located by electrical stimulation and characterized as mechanosensitive or not by blunt probing, mucosal stroking, and circumferential stretch. Intracolonic zymosan produced persistent colorectal hypersensitivity (>24 days) associated with brief colorectal inflammation. Pelvic nerve muscular-mucosal but not muscular mechanosensitive afferents recorded from mice with colorectal hypersensitivity exhibited persistent sensitization. In addition, the proportion of MIAs (relative to control) was significantly reduced from 27% to 13%, whereas the proportion of serosal afferents was significantly increased from 34% to 53%, suggesting that MIAs acquired mechanosensitivity. PGP9.5 immunostaining revealed no significant loss of colorectal nerve fiber density, suggesting that the reduction in MIAs is not due to peripheral fiber loss after intracolonic zymosan. These results indicate that colorectal MIAs and sensitized muscular-mucosal afferents that respond to stretch contribute significantly to the afferent input that sustains hypersensitivity to CRD, suggesting that targeted management of colorectal afferent input could significantly reduce patients' complaints of pain and hypersensitivity.

Rectal bleeding and hemostatic disorders induced by dabigatran etexilate in 2 elderly patients.

OBJECTIVE: To report rectal bleeding associated with hemostatic disorders in 2 elderly patients treated with dabigatran etexilate. CASE SUMMARY: A 79-year-old woman (weight, 69 kg) was hospitalized in a gastroenterology unit for severe rectal bleeding. She had been treated for 2 months with dabigatran etexilate 110 mg twice daily for chronic atrial fibrillation. On admission, her creatinine clearance (CrCl) was 20.7 mL/min/1.73 m(2), prothrombin time (PT) less than 10% (reference range 70-130%), and international normalized ratio (INR) 14.5 (venous blood). Eleven days after admission, hematologic and renal function were normalized and rectal bleeding stopped. An 84-year-old man (weight, 71 kg) was admitted for rectal bleeding with acute renal failure and dehydration that began while he was treated with dabigatran etexilate 110 mg twice daily for atrial fibrillation. On admission, CrCl was 33.5 mL/min/1.73 m(2), PT 13%, and INR 7.53 (venous blood). Dabigatran etexilate was stopped on admission. At the end of the hospitalization, CrCl was 66.5 mL/min/1.73 m(2), PT 54%, and INR 1.53. In both cases, an objective causality assessment revealed that those adverse reactions were probably related to dabigatran etexilate. DISCUSSION: In these 2 cases of rectal bleeding during dabigatran etexilate therapy, coagulation monitoring showed elevated PT and INR; neither patient had been exposed to vitamin K antagonists. These cases indicate the importance of PT and INR monitoring when using dabigatran etexilate, mainly in patients with a high risk of overdose, such as elderly patients or those with renal function impairment. CONCLUSIONS: It is critical to identify and subsequently manage dabigatran etexilate toxicity because there is no specific antidote to reverse the drug's anticoagulant effects.

[Colonic Mass Secondary to Sevelamer-associated Rectal Ulcer].

The phosphorous balance is clinically important in increasing the long-term outcomes and preventing complications of end-stage renal disease. Sevelamer is a phosphate binder used widely to regulate hyperphosphatemia. On the other hand, gastrointestinal side effects increase with increasing sevelamer intake. A 29-year-old male with end-stage renal disease of IgA nephropathy on maintenance hemodialysis was admitted for diffuse alveolar bleeding and pneumonia. He presented with a low-grade fever and watery diarrhea tinged with blood. Initially, a Clostridioides difficile-associated diarrhea treatment was started with positive findings of Clostridioides difficile toxin and culture. Despite this, there was no improvement in the symptoms even with the appropriate antibiotic treatment. Computed tomography of the abdomen and pelvis revealed an occlusive mass in the rectum and secondary obstructive changes in the sigmoid colon. The initial suspicion was a malignancy or fungal infection. Sigmoidoscopy with a biopsy identified the mass as a lump of mucous material with the entire lumen covered with exudate. The subsequent histopathology examination revealed a colonic mucosal injury and characteristic "fish scale"-like sevelamer crystals in the exudate. The diagnosis of a sevelamer-induced rectal ulcer was made. We report this case of a sevelamer-associated rectal ulcer of the sigmoid.

Optimization of prostate brachytherapy techniques with polyethylene glycol-based hydrogel spacers: A systematic review.

PURPOSE: The objective of this overview was to critically evaluate the effect of polyethylene glycol (PEG)-based hydrogel spacers during prostate brachytherapy with regard to dosimetric and clinical benefits, as well as procedure-related toxicity. METHODS AND MATERIALS: A systematic search in the PubMed database was performed. RESULTS: A total of 12 studies, involving 615 patients with PEG hydrogel injection, were included. Overall, patients well tolerated the implantation of PEG hydrogel spacers with an excellent safety profile. However, although there were some procedure-related complications, rates of these complications were very rare. Toxicities related to the spacer were limited to Grade 1 rectal discomfort and pain (9/615 patients), Grade 2 rectal ulceration (1 in 615 patients), perineal abscess (1 in 615 patients), and bacterial prostatitis (2/615 patients) according to Common Terminology Criteria for Adverse Events v4.0 grading scheme. The application of PEG hydrogel spacers significantly reduced radiation doses to the rectum during prostate brachytherapy in the different setting. Although there was no prospective randomized clinical trial, retrospective studies showed that reducing rectal doses by the implantation of PEG hydrogel may result in an improvement in rectal toxicity. CONCLUSIONS: The insertion of hydrogel spacers is safe, resulting in a significant decrease in rectal doses. This may lead to a reduction in rectal or gastrointestinal toxicity. Prospective randomized clinical trials are warranted to confirm the clinical impact of rectal dosimetric improvements.

Association between opioid usage and rectal dysfunction in constipation: A cross-sectional study of 2754 patients.

BACKGROUND: Opioid use has reached epidemic proportions. In contrast to the known effect of opioids on gut transit, the effect on rectal sensorimotor function has not been comprehensively investigated. METHODS: Cross-sectional (hypothesis-generating) study of anorectal physiology studies in 2754 adult patients referred to a tertiary unit (2004-2016) for investigation of functional constipation (defined by "derived" Rome IV core criteria). Statistical associations between opioid usage, symptoms, and anorectal physiological variables were investigated. Opioids were sub-classified as prescriptions for mild-moderate or moderate-severe pain. KEY RESULTS: A total of 2354 patients (85.5%) were classified as non-opioid users, 162 (5.9%) as opioid users for mild-moderate pain, and 238 (8.6%) for moderate-severe pain. Opioids for moderate-severe pain were associated with increased symptomatic severity (Cleveland Clinic constipation score 18.5 vs 15.1; mean difference 2.9 [95%-CI 2.3-3.6]; P < .001), rectal hyposensitivity (odds ratio 1.74 [95%-CI 1.23-2.46]; P = .002), functional evacuation disorders (odds ratio 1.73 [95%-CI 1.28-2.34]; P < .001), and delayed whole-gut transit (odds ratio 1.68 [95%-CI 1.19-2.37]; P = .003). Differences in anorectal variables between opioid users for mild-moderate pain and non-opioid users were not statistically significant. Hierarchical opioid use (non vs mild-moderate vs moderate-severe) was associated with decreasing proportions of patients with no physiological abnormality on testing (40.2% vs 38.1% vs 29.2%) and increasing proportions with both delayed whole-gut transit and rectal sensorimotor dysfunction (16.6% vs 17.5% vs 28.5%). CONCLUSIONS AND INFERENCES: Opioid use is over-represented in patients referred for investigation of constipation. Opioids for moderate-severe pain are associated with rectal sensorimotor abnormalities. Further studies are required to determine whether this association indicates causation.

[Rectal perforation in a patient treated with combination chemotherapy for lung cancer].

A 74-year old man was treated with first-cycle chemotherapy of paclitaxel (70 mg/m2=110 mg day 1, 8, 15) and carboplatin (AUC5=500 mg day 1) for lung cancer (c-T3N2M0, stage III A). On day 6 abdominal pain appeared, while on day 7 abdominal CT showed a perforation of the digestive tract. Thirty-three hours after the onset he underwent Hartmann operation during which we recognized a perforation 1.7 cm in size in the rectum. Although the cause of the perforation was unknown from the pathological findings, anticancer agents were suspected to be involved. Perforation should be taken into consideration in connection with acute abdominal disease after chemotherapy.

Thrombocytopaenia: a serious side effect of diazoxide.

A 2.5-year-old boy with a history of (transient) congenital hyperinsulinism was admitted to the paediatric ward with recurrent hypoglycaemia. Diazoxide 5 mg/kg/day and hydrochlorothiazide 2 mg/kg/day were initiated. After increasing the dose of diazoxide to 10 mg/kg/day, the child developed mild rectal bleeding, petechiae, epistaxis and haematemesis. Blood screening showed severe thrombocytopaenia. Diazoxide and hydrochlorothiazide were stopped, and his platelet count normalised. Drug rechallenge was positive. Drug-induced immune thrombocytopaenia was diagnosed.

Cytoprotective efficacy of amifostine against radiation- induced rectal toxicity: objective and subjective grading scales for radiomucositis.

Curative radiation therapy of pelvic malignancies, frequently results in dose limiting toxicities such as serous, mucoid, or more rarely, bloody diarrhea. Several studies have evaluated the cytoprotective effects of amifostine in preventing rectal mucositis associated with radiation treatment. We searched Medline for published comparative studies that evaluated the use of amifostine to reduce radiation-induced toxicity associated with pelvic irradiation. In ten studies there was an evidence-based cytoprotection (P less than 0.05)by amifostine. Although results are variable, current evidence suggests that amifostine may have a radioprotective effect in the rectal mucosa, particularly when administered intrarectally. Significant improvements were seen in both symptomatic and objective(rectosigmoidoscopy) end points. There is a need to conduct well-designed clinical trials with sufficient numbers of participants to confirm these findings together with a cost benefit study. Objective measurements using rectosigmoidoscopy are superior to subjective measures such as WHO or RTOG/EORTC toxicity grading scales.

Rectal ulcer due to Kayexalate deposition - an unusual case.

Sodium polystyrene sulfonate (PSP) or Kayexalate is a cation-exchange resin, widely used in the management of hyperkalaemia due to renal disease. A rare, yet potentially dangerous, adverse event related to sodium polystyrene sulfonate use is intestinal mucosal injury, especially in the colon. The injury to the gastrointestinal mucosa can range from mild and superficial to wall necrosis and bowel perforation. The mechanism that leads to mucosal damage remains unclear. However, it is believed that sorbitol, commonly given to counteract PSP's tendency to cause constipation, may play an important role in the development of gastrointestinal injury. Other potential risk factors are uraemia or end-stage renal disease, hemodynamic instability, solid organ transplantation, postoperative status and concomitant opioid administration. The authors present a case of diarrhoea and haematochezia after the administration of PSP without sorbitol, in a patient with hyperkalaemia due to acute kidney injury, in the absence of other risk factors. A colonoscopy was performed and revealed a rectal ulcer which histological findings were suggestive of mucosal injury due to Kayexalate deposition. This case supports the concept that this widely used drug can itself, without sorbitol, cause injury to the gastrointestinal wall. Even though this is a rare adverse effect, the widespread use of this medication may put a large population at risk.