Efficacy of bethanechol chloride in the treatment of radiation-induced xerostomia in patients with head and neck cancer: A systematic review and meta-analysis.

BACKGROUND AND PORPUSE: Salivary glands sustain collateral damage following radiotherapy (RT) to treat cancers of the head and neck, leading to complications, including xerostomia and hyposalivation. This systematic review (SR) with meta-analysis was performed to determine the effectiveness of bethanechol chloride in preventing salivary gland dysfunction in this context. MATERIALS AND METHODS: Medline/Pubmed, Embase, Scopus, LILACS via Portal Regional BVS and Web of Science were searched electronically in accordance with the Cochrane manual and reported PRISMA guidelines. RESULTS: 170 patients from three studies were included. Results from the meta-analysis suggest that bethanechol chloride is associated with increases in: whole stimulating saliva (WSS) after RT (Std. MD 0.66, 95% CI 0.28 to 1.03, P < 0.001); whole resting saliva (WRS) during RT (Std. MD 0.4, 95% CI 0.04 to 0.76, P = 0.03); and WRS after RT (Std. MD 0.45, 95% CI 0.04 to 0.86, P = 0.03). CONCLUSION: The present study suggests that bethanechol chloride therapy may be effective in patients with xerostomia and hyposalivation.

Bethanechol used to prevent salivary gland dysfunction in patients submitted to radioactive iodine therapy: A double blind, placebo-controlled, randomized study.

Symptoms related to salivary gland damage are one of the most frustrating complications after radioactive iodine (131I) therapy. To the best of our knowledge, this is the first study that aimed to evaluate the prophylactic effect of Bethanechol on the radioiodine content of salivary gland. Fifty patients who were referred to 131I therapy were randomized into Bethanechol and placebo groups. Patients received Bethanechol or Placebo (25 mg, 2 times daily), starting 2 h after 131I therapy to 1-month.  Both groups were compared at baseline, 10, 30 and 90 days after 131I therapy based on the following: symptoms related to salivary gland damage; unstimulated whole saliva (UWS) and quality of life using University of Washington Quality of Life 4 questionnaire. Bethanechol group presented significantly lower complaints of dry mouth on 10 (p = 0.047) and 30 (p = 0.003) days compared with placebo. Salivary gland pain and swelling were more frequent among placebo patients at 10 days (p = 0.047). Comparison of the two groups by UWS, no statistical difference was found. Placebo group presented worse score related to activity (p = 0.034), saliva (p = 0.05) and humor (p = 0.05) at 10 days; palate (p = 0.05) and saliva (p = 0.05) at 1 month. Interestingly, Bethanechol patients who received 131I dose > 125mCi, showed better xerostomia indices when compared to the Placebo with same dose. Bethanechol during 131I therapy was found to be effective in decreasing the acute salivary gland damage with impact on patients' quality of life.

Postoperative interventions for preventing bladder dysfunction after radical hysterectomy in women with early-stage cervical cancer.

BACKGROUND: Bladder dysfunction is a common complication following radical hysterectomy, caused by the damage to pelvic autonomic nerves that innervate the muscles of the bladder, urethral sphincter, and pelvic floor fasciae. Bladder dysfunction increases the rates of urinary tract infection, hospital visits or admission, and patient dissatisfaction. In addition, bladder dysfunction can also negatively impact patient quality of life (QoL). Several postoperative interventions have been proposed to prevent bladder dysfunction following radical hysterectomy. To our knowledge, there has been no systematic review evaluating the effectiveness and safety of these interventions for preventing bladder dysfunction following radical hysterectomy in women with cervical cancer. OBJECTIVES: To evaluate the effectiveness and safety of postoperative interventions for preventing bladder dysfunction following radical hysterectomy in women with early-stage cervical cancer (stage IA2 to IIA2). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 4) in the Cochrane Library, MEDLINE via Ovid (1946 to April week 2, 2020), and Embase via Ovid (1980 to 2020, week 16). We also checked registers of clinical trials, grey literature, conference reports, and citation lists of included studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) evaluating the effectiveness and safety of any type of postoperative interventions for preventing bladder dysfunction following a radical hysterectomy in women with stage IA2 to IIA2 cervical cancer. DATA COLLECTION AND ANALYSIS: Two review authors independently selected potentially relevant RCTs, extracted data, assessed risk of bias, compared results, and made judgments on the quality and certainty of the evidence. We resolved any disagreements through discussion or consultation with a third review author. Outcomes of interest consisted of spontaneous voiding recovery one week after the operation, quality of life (QoL), adverse events, post-void residual urine volume one month after the operation, urinary tract infection over the one month following the operation, and subjective urinary symptoms. MAIN RESULTS: We identified 1464 records as a result of the search (excluding duplicates). Of the 20 records that potentially met the review criteria, we included five reports of four studies. Most of the studies had unclear risks of selection and reporting biases. Of the four studies, one compared bethanechol versus placebo and three studies compared suprapubic catheterisation with intermittent self-catheterisation. We identified two ongoing studies. Bethanechol versus placebo The study reported no information on the rate of spontaneous voiding recovery at one week following the operation, QoL, adverse events, urinary tract infection in the first month after surgery, and subjective urinary symptoms for this comparison. The volume of post-void residual urine, assessed at one month after surgery, among women receiving bethanechol was lower than those in the placebo group (mean difference (MD) -37.4 mL, 95% confidence interval (CI) -60.35 to -14.45; one study, 39 participants; very-low certainty evidence). Suprapubic catheterisation versus intermittent self-catheterisation The studies reported no information on the rate of spontaneous voiding recovery at one week and post-void residual urine volume at one month following the operation for this comparison. There was no difference in risks of acute complication (risk ratio (RR) 0.77, 95% CI 0.24 to 2.49; one study, 71 participants; very low certainty evidence) and urinary tract infections during the first month after surgery (RR 0.77, 95% CI 0.53 to 1.13; two studies, 95 participants; very- low certainty evidence) between participants who underwent suprapubic catheterisation and those who underwent intermittent self-catheterisation. Available data were insufficient to calculate the relative measures of the effect of interventions on QoL and subjective urinary symptoms. AUTHORS' CONCLUSIONS: None of the included studies reported rate of spontaneous voiding recovery one week after surgery, time to a post-void residual volume of urine of 50 mL or less, or post-void residual urine volume at 6 and 12 months after surgery, all of which are important outcomes for assessing postoperative bladder dysfunction. Limited evidence suggested that bethanechol may minimise the risk of bladder dysfunction after radical hysterectomy by lowering post-void residual urine volume. The certainty of this evidence, however, was very low. The effectiveness of different types of postoperative urinary catheterisation (suprapubic and intermittent self-catheterisation) remain unproven.

Bethanechol: Is it still being prescribed for bladder dysfunction in women?

PURPOSE: Few medical treatment options exist for detrusor underactivity or urinary retention in women. Bethanechol, a cholinergic agonist, may improve detrusor contractility in these conditions; however, its clinical efficacy is limited. We sought to examine the patterns of Bethanechol use by physicians in an ambulatory care setting using a national database to determine if it is still prescribed for patients with bladder dysfunction. MATERIALS AND METHODS: The National Ambulatory Medical Care Survey (NAMCS) database was queried for a sample of patient visits to office-based physicians from 2003-2013. Visits were included for women aged 18 years or older with diagnosed lower urinary tract symptoms (LUTS), neurogenic bladder, or urinary retention based on ICD-9-CM codes. Visits in which Bethanechol was prescribed were analysed with descriptive statistics. Sampling weights were adjusted for nonresponders to yield an unbiased national estimate of ambulatory care visits. RESULTS: Out of a weighted sample of 17 321 630 included patient visits, 132 281 (0.8%) visits included a prescription for Bethanechol. Patients prescribed Bethanechol had a mean age of 62.3 ± 2.1 and were predominantly Caucasian (67%) followed by African American (18%). The primary diagnosis associated with Bethanechol was atony of bladder (35%), urinary retention (20%), neurogenic bladder (18%), urinary incontinence (16%), and incomplete bladder emptying (10%). Visits were primarily for chronic conditions (63%). It was typically prescribed as a continued medication (79%) most often by urologists (92%) followed by internal medicine clinicians (8%). CONCLUSIONS: Bethanechol continues to be prescribed in elderly women primarily for detrusor atony, urinary retention, or incomplete bladder emptying.

Bronchoscopy in neonates with severe bronchopulmonary dysplasia in the NICU.

OBJECTIVES: To describe the findings, resulting changes in management, and safety profile of flexible bronchoscopy in the neonates with severe bronchopulmonary dysplasia. STUDY DESIGN: This was a retrospective case series of twenty-seven neonates with severe bronchopulmonary dysplasia who underwent flexible bronchoscopy in the neonatal intensive care unit. RESULTS: Flexible bronchoscopy revealed airway pathology in 20/27 (74%) patients. Tracheomalacia 13/27 (48%), bronchomalacia 11/27 (40.7%), and airway edema 13/27 (48%) were the most common findings. Bronchoalveolar lavage (BAL) was performed in 17 patients. BAL culture revealed a microorganism in 12/17 (70.5%) cases. Findings from bronchoscopy resulted in change in clinical management in 17/27 (63%) patients. Common interventions included initiation of antibiotics (37%) and treatment of tracheobronchomalacia with bethanechol (22.2%), atrovent (18.5%), and PEEP titration (18.5%). Bronchoscopy was performed without significant complication in 26/27 (97%) patients. CONCLUSION: Flexible bronchoscopy can be a safe and useful tool for the management of neonates with severe bronchopulmonary dysplasia.

New technology assessment and current and upcoming therapies for underactive bladder.

BACKGROUND AND AIMS: Stakeholders from around the world came together to address the unmet needs of underactive bladder (UAB) at the 3rd International Congress for Underactive Bladder. METHODS: The main recommendation from the regulatory working group is a need for a meeting of UAB stakeholders and regulatory agencies including the FDA to discuss guidance for regulatory trial design for devices, drugs, and/or biologics for UAB. RESULTS: The following issues to be discussed and agreed upon for UAB trials: 1) Appropriate inclusion and exclusion criteria. 2) Should residual urine volume be the primary outcome parameter and how often should it be measured? 3) Are there secondary measures that should have a place in UAB trials, such as change in the number of catheterizations, quality of life measures, etc.? 4) Use and format of bladder voiding and catheterization diary for trials. 5) Define role and technique of urodynamics in UAB trials. Are urodynamics required to monitor, and possibly exclude, individuals with high pressure voiding induced by bladder prokinetic therapies? 6) Development and use of UAB questionnaires. DISCUSSION AND CONCLUSION: The UAB regulatory working group recognizes the path forward should include engaging the FDA and other regulatory organizations that may harmonize and formalize guidance for regulatory trial designs for therapeutics for UAB.

Salivary hypofunction: An update on therapeutic strategies.

OBJECTIVE: To perform a literature review addressing the therapeutic strategies for salivary hypofunction. BACKGROUND: Qualitative and quantitative salivary dysfunctions predispose to changes in the oral mucosa and teeth, cause impairment to oral functions and negative impact on quality of life. MATERIALS AND METHODS: A MEDLINE/PubMed search was conducted using the terms "Xerostomia" AND, "Saliva Artificial" OR, "Citric Acid," "Malic Acid," "Chewing Gum," "Acupuncture" OR, "Pilocarpine" OR, "Bethanechol" OR, "Cevimeline" OR, "Hyperbaric Oxygen Therapy" OR, "Stem Cell Therapy" OR "Genetic Therapy" and their Mesh Terms. RESULTS: We selected 25 clinical trials investigating the effects of salivary substitutes, chewing gum, malic and citric acids, pilocarpine, cevimeline, bethanechol, acupuncture, hyperbaric oxygen therapy and regenerative therapies on salivary hypofunction. In most studies, the number of participants was low and the follow-up times short. The therapeutic modalities were classified according to the level of evidence on salivary dysfunction. CONCLUSIONS: Pilocarpine and cevimeline had the strongest evidence of beneficial effect on salivary hypofunction. Citric and malic acids increase salivary flow but also increase the risk of erosion and dental caries. There are no controlled clinical trials supporting the efficacy of acupuncture, stem cell therapy and gene therapy on salivary dysfunction, although clinical observations suggest a promising effect. There is no evidence supporting salivary substitutes, chewing gum, bethanechol or hyperbaric oxygen on the treatment of salivary hypofunction.

Malakoplakia of the large intestine: an incidental extremely rare finding.

Malakoplakia is a rare inflammatory disease, most commonly found in the urinary tract. It appears be related to a functional deficiency of macrophages, resulting in an inability to destroy digested bacteria and it is associated with various conditions that cause immunodeficiency. A rare case of malakoplakia of the colon in a healthy 68-year old male is presented. The patient underwent emergency surgery with colon resection and an end stoma with closure of the distal bowel (Hartmann's procedure), due to incarcerated ventral hernia and sigmoid-colon rupture. He underwent reversal of the Hartmann's procedure four months after the initial operation. The histological examination from the anastomotic rings revealed Michaelis-Gutmann bodies that are pathognomonic of malakoplakia. He received per os ciprofloxacin, bethanecol and ascorbic acid for 12 months. Follow-up endoscopy did not exhibit any signs of the disease. A case of a healthy patient presenting with malakoplakia without any underlying disease that causes immunodeficiency is extremely rare. Treatment of malakoplakia involves the eradication of microorganisms. Cholinergic agonists, such as bethanechol and ascorbic acid, as well as antimicrobial treatment with trimpethoprim/sulphamethoxazol and rifampicin are most commonly being used. Long-term antimicrobial treatment has been reported (6 months to 3 years).

Terapia farmacológica y avances terapéuticos en xerostomía e hiposalivación / Pharmacological therapy and therapeutic advancesin xerostomy and hyposalivation

La saliva juega un rol determinante en el mantenimiento y función de los tejidos orales, donde un decremento en los niveles del flujo salival conllevan a una hiposalivación o hiposialia, trayendo consigo una serie de características que propician un ambiente ideal para la instalaciónde microorganismos oportunistas y condiciones nocivas para la saludoral y sistémica de los pacientes. Hoy en día existen múltiples causas que conllevan a una hiposialia, entre ellas el síndrome de Sjõgren, la radioterapia de haz externo, entre otras, los cuales se han puesto a prueba mediante sialogogos farmacológicos como pilocarpina, cevimelina, betanecoly carbacolina, además de alternativas terapéuticas para revertir los signos obtenidos por la hiposalivación y mitigar los síntomas de xerostomía. El objetivo del presente es realizar una revisión de literatura sobre el tratamiento farmacológico en hiposalivación y xerostomía ensíndrome de Sjõgren y radioterapia de haz externo.

Saliva plays a determinant role in the maintenance and function of oral tissues, where a decrease in salivary flow levels leads to hyposalivation or hyposialia, bringing with it a series of characteristics that provide anideal environment for the installation of opportunistic microorganisms and conditions harmful to the oral and systemic health of patients.Today there are many causes that lead to hyposialia, including Sjögren’ssyndrome, external beam radiotherapy, among others, which have beentested by pharmacological sialogogs such as pilocarpine, cevimelin, betanecol and carbacoline, in addition to therapeutic alternativesto reverse the signs obtained by hyposalivation and to mitigate the symptoms of xerostomia. The objective of the present is to make a reviewof the literature on the pharmacological treatment in hyposalivation and xerostomia in Sjögren’s syndrome and external beam radiotherapy.

Influence of bethanechol on salivary parameters in irradiated patients.

BACKGROUND: Some studies have shown evidence that the prophylactic use of bethanechol chloride (BC) may be useful in preventing the incidence and/or severity of xerostomia (XT). However, the indication of BC in irradiated patients with XT needs to be better characterized. The study aimed to evaluate the influence of BC on XT, salivary flow rate, and salivary composition in patients previously submitted to head and neck radiotherapy. MATERIAL AND METHODS: Forty five irradiated patients complaining of XT used 50 mg/day of BC for 3 months, and the salivary parameters were evaluated in 4 Phases (Before BC therapy, after one month of BC, 2 months of BC, and 3 months of BC). Biochemical analysis included buffering capacity; pH; total protein concentration (TP); amylase concentration (AM); catalase (CAT) and peroxidase (PX) activities. In addition, unstimulated and stimulated salivary flow rates were determined and XT was classified. RESULTS: According to the XT grading system used, patients showed improvement in XT between Phase 1, and Phases 2, 3 and 4. In addition, some changes were observed in TP concentration (decreased); AM concentration (increased); and PX and CAT activities (decreased and increased, respectively) after Phase 2, for stimulated saliva collection (p<0.05). CONCLUSIONS: Our results suggested that when BC was used to treat salivary gland dysfunction induced by head and neck radiotherapy, improvement in XT symptoms, and some changes in saliva composition were shown.

Double blind randomized prospective trial of bethanechol in the prevention of radiation-induced salivary gland dysfunction in head and neck cancer patients.

This study assessed the prophylactic bethanechol use to prevent salivary gland dysfunction during radiotherapy. A total of 97 head and neck cancer patients were allocated into two groups: Bethanechol or Placebo. Bethanechol group presented significantly improve of salivary parameters. Bethanechol was effective in decreasing the salivary gland damage.

Effects of bethanechol chloride and distigmine bromide on postvoiding residual volume in patients with underactive bladder.

AIM: The efficacy of cholinergic drugs for reduction of post-voiding residual volume (PVR) in patients with underactive bladder is still controversial. This study was performed to examine whether cholinergic drugs have such an effect on PVR. METHODS: Patients with underactive bladder treated for more than two months with cholinergic drugs, which were later discontinued, were extracted retrospectively based on their charts. The changes in PVR, cholinesterase activity (ChE), renal function, and voiding function before and after discontinuation of cholinergic drugs were reviewed and analyzed. RESULTS: Twenty-nine patients were included in this study. In multiple linear regression analysis, the discontinuation of distigmine bromide (DB) was indicated as a significant covariate for PVR increase and ChE increase, while bethanechol chloride (BC) was not a significant covariate. The increase in ChE was significantly correlated with both PVR and voided volume after discontinuation of cholinergic drugs. CONCLUSION: DB could reduce PVR via a decrease in ChE. However, BC at doses up to 60 mg did not reduce PVR. DB may be recommended for the reduction of PVR in patients with underactive bladder.

An adult case of cerebral malakoplakia successfully cured by treatment with antibiotics, bethanechol and ascorbic acid.

Cerebral malakoplakia is a very rare chronic inflammatory disease. We herein report the case of a 49-year-old female who presented with a slowly progressive speech disturbance and right hemiparesis. Computed tomography and magnetic resonance imaging showed irregular enhanced mass lesions with numerous scattered areas of calcification in the left insula, thalamus and basal ganglia. Histopathologically, the biopsy specimen showed basophilic laminated inclusion bodies and intracellular and extracellular calculospherules, usually with a typical targetoid appearance (Michaelis-Gutmann bodies). Treatment with antibiotics, bethanechol and ascorbic acid improved her symptoms in association with a decrease in the abnormal calcification and enhancement. The cerebral malakoplakia mimicked a brain tumor in terms of the patient's clinical course and neuroradiological image findings; however, it was successfully cured with medical treatment. This case provides evidence that the pathogenesis of cerebral malakoplakia is deeply tied to bacterial infection and that medical treatment is effective in cases of this disease.

[Acute urinary retention in children: initial manifestation of caudal regression syndrome]. / Akuter Harnverhalt im Kleinkindalter : Erstmanifestation eines kaudalen Regressionssyndroms.

Caudal regression syndrome is a rare and sporadic congenital developmental defect of the lower spinal segments and the neural tube. Movement disorders and sensory neurological deficits of the lower extremities in conjunction with impaired bladder and bowel control are the major symptoms. Abnormal visual aspects of the sacral region in combination with maternal gestational diabetes are further diagnostic indications. This article reports the unusual case of a toddler presenting with acute urinary retention as the initial symptom of caudal regression syndrome.

Malakoplakia in a healthy young female patient.

Malakoplakia is a rare granulomatous disease that occurs commonly in the urinary tract and secondarily in the gastrointestinal tract. Most reported cases of malakoplakia are associated with immunosuppressive diseases or chronic prolonged illness. Here, we report a rare case of malakoplakia in a young healthy adolescent without any underlying disease. A 19-year-old female was referred to our hospital following the discovery of multiple rectal polyps with sigmoidoscopy. She had no specific past medical history but complained of recurrent abdominal pain and diarrhea for 3 months. A colonoscopy revealed diverse mucosal lesions including plaques, polyps, nodules, and mass-like lesions. Histological examination revealed a sheet of histiocytes with pathognomonic Michaelis-Gutmann bodies. We treated the patient with ciprofloxacin, the cholinergic agonist bethanechol, and a multivitamin for 6 months. A follow-up colonoscopy revealed that her condition was resolved with this course of treatment.

[A pilot trial on the treatment of gastroesophageal reflux-related cough in infants].

OBJECTIVE: Diagnosing asthma in infancy is largely made on the basis of the symptoms of cough and wheezing. A similar presentation can be seen in neurologically normal infants with excessive gastroesophageal reflux (GER). There are no randomized placebo controlled studies in infants using proton pump inhibitors (PPI) alone or in addition to prokinetic agents. The primary objective was to confirm the presence of excessive GER in a population of infants that also had respiratory symptoms suggestive of asthma. Second, in a randomized placebo-controlled fashion, we determined whether treatment of GER with bethanacol and omeprazole could improve these respiratory symptoms. METHODS: Infants (n=22) with a history of chronic cough and wheeze were enrolled, if they had evidence of GER by history and an abnormal pH probe or gastric emptying scan. Infants were randomly allocated to four treatment groups: placebo/placebo (PP), omeprazole plus bethanacol (OB), omeprazole/placebo (OP), bethanacol/placebo (BP). Evaluations by clinic questionnaire and exam, home diary, and pH probe data were done before, after study-medication and after open label of OB. RESULTS: Nineteen children were studied. PP did not affect GER or respiratory symptoms, and did not decrease GER measured by pH probe. In contrast, OB decreased GER as measured by pH probe indices and parental assessment. In association, OB significantly decreased daytime coughing and improved respiratory scores. No adverse effects were reported. CONCLUSIONS: In infants with a clinical presentation suggestive of chronic GER-related cough, the use of omeprazole and bethanacol appears to be viable therapeutic option.

Bethanechol for buprenorphine-related urinary hesitancy: a case series.

Constipation is a well-known side effect of buprenorphine, but urinary hesitancy is less frequently discussed and may go unrecognized. Reported are the 2 cases of men older than 50 years who experienced disabling urinary hesitancy with buprenorphine and naloxone combination (suboxone) and were successfully treated with bethanechol, a cholinergic medication.

Bethanechol chloride for the prevention of bladder dysfunction after radical hysterectomy in gynecologic cancer patients: a randomized controlled trial study.

BACKGROUND: Bethanechol chloride is considered as a treatment in patients with high postvoid residual urine (PVR). It enhances detrusor muscle contraction, resulting in higher maximum flow rate, higher detrusor pressure at maximum flow, and lower PVR. The efficacy of this agent in patients after radical hysterectomy is unclear. We aim to evaluate the efficacy of bethanechol chloride compared with placebo for the prevention of bladder dysfunction after type III radical hysterectomy. METHODS: Gynecologic cancer patients who underwent type III radical hysterectomy were randomized by computer-generated schedule to assign patients in a 1:1 ratio into 2 groups. The treatment group received bethanechol chloride (Ucholine 20 mg 3 times a day on the third to seventh postoperative day), and the control group received placebo. Patients and physicians were masked to treatment allocation. The primary end point was the rate of urethral catheter removal at 1 week postoperatively. If PVR was more than 30% of voided volume, the urethral catheter was reinserted, and medication would be continued but not for more than 1 month. This study was registered as ISRCTN92687416. FINDINGS: There were 31 patients in each group without significant difference in baseline characteristics. Twenty-one patients (67.7%) in the treatment group and 12 patients (38.7%) in the control group had the urethral catheter removed at 1 week postoperatively (P = 0.04). Median duration of urethral catheterization was shorter in the treatment group (7 and 14 days, P = 0.03). However, the PVR and the incidence of urinary tract infection at 1 month postoperatively were not significantly different. Nine patients (29%) in the treatment group had adverse events such as nausea, abdominal distension, and abdominal cramping, which was higher than the control group (1 patient, 3.2%; P = 0.01). However, no patients required any medical treatments. CONCLUSIONS: Bethanechol chloride decreases the duration of urethral catheterization in patients who underwent type III radical hysterectomy with manageable adverse events.