A Percutaneous Endoscopic Colostomy Tube to the Rescue.

Percutaneous endoscopic colostomy (PEC) tube placement is a minimally invasive procedure used to treat recurrent colonic pseudo-obstruction, sigmoid volvulus, chronic intractable constipation, and neurogenic bowel. PEC is a viable treatment alternative for patients who have failed conservative therapies and are deemed high risk for surgical management. We present a case of acute colonic pseudo-obstruction after Clostridioides difficile infection that was unresponsive to medical treatment or endoscopic decompression. A PEC tube was placed into the transverse colon with successful resolution of the colonic distension.

Loop-and-let-go technique for the management of symptomatic large colonic lipoma.

Video 1We depict (1) identification of a large lipoma in the sigmoid colon; (2) radial echo endoscopy confirming diagnosis; (3) removal with the loop-and-let-go technique; (4) ex vivo demonstration of the technique; and (5) an interval follow-up demonstrating healing of the lesion.

Bridging to Allotransplantation-Is Pig Liver Xenotransplantation the Best Option?

In the past 20 y, the number of patients in the United States who died while waiting for a human donor liver totaled >52 000. The median national wait time for patients with acute liver failure and the most urgent liver transplant listing was 7 d in 2018. The need for a clinical "bridge" to allotransplantation is clear. Current options for supporting patients with acute liver failure include artificial liver support devices, extracorporeal liver perfusion, and hepatocyte transplantation, all of which have shown mixed results with regard to survival benefit and are largely experimental. Progress in the transplantation of genetically engineered pig liver grafts in nonhuman primates has grown steadily, with survival of the pig graft extended to almost 1 mo in 2017. Further advances may justify consideration of a pig liver transplant as a clinical bridge to allotransplantation. We provide a brief history of pig liver xenotransplantation, summarize the most recent progress in pig-to-nonhuman primate liver transplantation models, and suggest criteria that may be considered for patient selection for a clinical trial of bridging by genetically engineered pig liver xenotransplantation to liver allotransplantation.

Prevalence and Risk Factors for Intraductal Papillary Mucinous Neoplasm in Patients With Chronic Kidney Disease: A Single-Center Case-Control Study.

OBJECTIVES: The exact prevalence for intraductal papillary mucinous neoplasm (IPMN) in patients with chronic kidney disease (CKD) remains unknown. In this single-center case-control study, we aimed to study the prevalence and risk factors for IPMN in patients with CKD. METHODS: We performed a retrospective case-control study comparing patients with and without CKD who had magnetic resonance imaging of the abdomen performed between January 2018 and December 2018. Patient demographic, clinical, and imaging metrics were extracted from chart review. The prevalence of IPMN was compared between the 2 groups. RESULTS: A total of 800 patient charts were reviewed. There were 400 patients with CKD compared with an age-matched control group of 400 patients without CKD. The total prevalence of IPMN in patients with CKD was 13.7% (55/400) compared with 7.8% (29/400; P = 0.002) in non-CKD patients. The prevalence of diabetes mellitus was significantly higher in the CKD group (41% vs 14%, P = 0.0001). The percentage of patients consuming alcohol was significantly higher in the non-CKD group (23% vs 35%, P = 0.002). CONCLUSIONS: Patients with CKD have a significantly higher prevalence of IPMN compared with non-CKD patients. Larger population-based studies are needed to confirm these findings.

Current Status of Endoscopic Resection of Gastric Subepithelial Tumors.

Most gastrointestinal (GI) subepithelial tumors (SETs) are identified incidentally during endoscopic examination and are located in the stomach. Some SETs are malignant or have the potential to become malignant. Tumors originating from deeper layers, such as the muscularis propria or serosa, are not easy to diagnose and resect. Current guidelines recommend yearly endoscopic surveillance of SETs smaller than 2 cm. This recommendation may not be cost-effective in managing GI SETs. Endoscopic resection results not only in obtaining sufficient tissue for pathological diagnosis but also in resection and curing the tumor. Many different endoscopic methods for resection of GI SETs have been published in the literature. To avoid confusion, we have divided these methods into standard endoscopic submucosal dissection, modified endoscopic submucosal dissection, submucosal tunneling endoscopic resection, and nonexposed and exposed endoscopic full-thickness resection. These procedures offer less invasive approaches than surgery for resection of GI SETs and may be the most cost-effective in taking care of patients with GI SETs.

Diabetic Gastroparesis and Nondiabetic Gastroparesis.

Gastroparesis can be divided into diabetic and nondiabetic, and the 3 main causes of gastroparesis are diabetic, postsurgical, and idiopathic. Delayed gastric emptying is the main manifestation of motility disorders for gastroparesis. Symptoms of gastroparesis are nonspecific and severity can vary. Nausea and vomiting are more common in diabetic gastroparesis whereas abdominal pain and early satiety are more frequent in idiopathic gastroparesis. Medication is still the mainstay of treatment of gastroparesis; however, the development of gastric electric stimulation and gastric peroral endoscopic pyloromyotomy brings more options for the treatment of diabetic and nondiabetic gastroparesis.

Safety and Surgical Outcomes of Same-day Anterior Urethroplasty.

OBJECTIVE: To evaluate the safety and feasibility of same-day anterior urethroplasty at our institution and define predictors of postoperative admission and surgical failure. METHODS: We retrospectively reviewed the charts of 118 consecutive anterior urethroplasties performed at a tertiary care center. Data were analyzed to detect predictors of postoperative admission and urethroplasty failure. The 30-day complications and long-term outcomes were compared between same-day and admitted patients. RESULTS: Ninety-two patients (78%) were discharged on the day of surgery. A penile stricture location compared with a bulbar stricture location (odds ratio: 13.4, P = .009) and having undergone more than 3 prior endoscopic stricture interventions (odds ratio: 10.2, P = .001) were significantly associated with postoperative admission. Patients with a ventral onlay approach were more likely to be discharged home (P = .03), whereas patients with combined repairs were more likely to be admitted (P = .04). Same-day urethroplasty did not increase 30-day postoperative complications, patient emergency room visits, unplanned clinic visits, or phone calls. Success rates did not differ between same-day (89%) and admitted (79%) cohorts, and no individual stricture characteristic was predictive of urethroplasty failure. CONCLUSION: Same-day anterior urethroplasty is safe and feasible and could help increase utilization of urethroplasty for urethral stricture disease.

Sex difference in the contribution of GABAB receptors to tibial neuromodulation of bladder overactivity in cats.

This study investigated the role of γ-aminobutyric acid subtype B (GABAB) receptors in tibial and pudendal neuromodulation of bladder overactivity induced by intravesical administration of dilute (0.5%) acetic acid (AA) in α-chloralose-anesthetized cats. To inhibit bladder overactivity, tibial or pudendal nerve stimulation (TNS or PNS) was applied at 5 Hz and two or four times threshold (T) intensity for inducing toe or anal sphincter twitch. TNS at 2T or 4T intensity significantly (P < 0.05) increased the bladder capacity to 173.8 ± 16.2 or 198.5 ± 24.1%, respectively, of control capacity. Meanwhile, PNS at 2T or 4T intensity significantly (P < 0.05) increased the bladder capacity to 217 ± 18.8 and 221.3 ± 22.3% of control capacity, respectively. CGP52432 (a GABAB receptor antagonist) at intravenous dosages of 0.1-1 mg/kg completely removed the TNS inhibition in female cats but had no effect in male cats. CGP52432 administered intravenously also had no effect on control bladder capacity or the pudendal inhibition of bladder overactivity. These results reveal a sex difference in the role of GABAB receptors in tibial neuromodulation of bladder overactivity in cats and that GABAB receptors are not involved in either pudendal neuromodulation or irritation-induced bladder overactivity.

Sacral neuromodulation of nociceptive bladder overactivity in cats.

AIMS: To investigate the effects of electrical stimulation of sacral dorsal/ventral roots on irritation-induced bladder overactivity, reveal possible different mechanisms under nociceptive bladder conditions, and establish a large animal model of sacral neuromodulation. METHODS: Intravesical infusion of 0.5% acetic acid (AA) was used to irritate the bladder and induce bladder overactivity in cats under α-chloralose anesthesia. Electrical stimulation (5, 15, or 30 Hz) was applied to individual S1-S3 dorsal or ventral roots at or below motor threshold intensity. Repeated cystometrograms (CMGs) were performed with/without the stimulation to determine the inhibition of bladder overactivity. RESULTS: AA irritation induced bladder overactivity and significantly (P < 0.05) reduced the bladder capacity to 62.6 ± 11.7% of control capacity measured during saline CMGs. At threshold intensity for inducing reflex twitching of the anal sphincter or toe, S1/S2 dorsal root stimulation at 5 Hz but not at 15 or 30 Hz inhibited bladder overactivity and significantly (P < 0.05) increased bladder capacity to 187.3 ± 41.6% and 155.5 ± 9.7% respectively, of AA control capacity. Stimulation of S3 dorsal root or S1-S3 ventral roots was not effective. Repeated stimulation of S1-S3 dorsal root did not induced a post-stimulation inhibition. CONCLUSIONS: This study established a cat model of sacral neuromodualation of nociceptive bladder overactivity. The results revealed that the mechanisms underlying sacral neuromodulation are different for nociceptive and non-nociceptive bladder activity.

Neurotransmitter Mechanisms Underlying Sacral Neuromodulation of Bladder Overactivity in Cats.

OBJECTIVE: To determine the role of opioid, ß-adrenergic, and metabotropic glutamate 5 receptors in sacral neuromodulation of bladder overactivity. MATERIAL AND METHODS: In α-chloralose anesthetized cats, intravesical infusion of 0.5% acetic acid (AA) irritated the bladder and induced bladder overactivity. Electric stimulation (5 Hz, 0.2 ms, 0.16-0.7V) of S1 or S2 sacral dorsal roots inhibited the bladder overactivity. Naloxone, propranolol, or MTEP were given intravenously (i.v.) to determine different neurotransmitter mechanisms. RESULTS: AA significantly (p < 0.05) reduced bladder capacity to 7.7 ± 3.3 mL from 12.0 ± 5.0 mL measured during saline infusion. S1 or S2 stimulation at motor threshold intensity significantly (p < 0.05) increased bladder capacity to 179.4 ± 20.0% or 219.1 ± 23.0% of AA control, respectively. Naloxone (1 mg/kg) significantly (p < 0.001) reduced the control capacity to 38.3 ± 7.3% and the bladder capacity measured during S1 stimulation to 106.2 ± 20.8% of AA control, but did not significantly change the bladder capacity measured during S2 stimulation. Propranolol (3 mg/kg) significantly (p < 0.01) reduced bladder capacity from 251.8 ± 32.2% to 210.9 ± 33.3% during S2 stimulation, but had no effect during S1 stimulation. A similar propranolol effect also was observed in naloxone-pretreated cats. In propranolol-pretreated cats during S1 or S2 stimulation, MTEP (3 mg/kg) significantly (p < 0.05) reduced bladder capacity and naloxone (1 mg/kg) following MTEP treatment further reduced bladder capacity. However, a significant inhibition could still be induced by S1 or S2 stimulation after all three drugs were administered. CONCLUSIONS: Neurotransmitter mechanisms in addition to those activating opioid, ß-adrenergic, and metabotropic glutamate 5 receptors also are involved in sacral neuromodulation.

Sympathetic ß-adrenergic mechanism in pudendal inhibition of nociceptive and non-nociceptive reflex bladder activity.

This study investigated the role of the hypogastric nerve and ß-adrenergic mechanisms in the inhibition of nociceptive and non-nociceptive reflex bladder activity induced by pudendal nerve stimulation (PNS). In α-chloralose-anesthetized cats, non-nociceptive reflex bladder activity was induced by slowly infusing saline into the bladder, whereas nociceptive reflex bladder activity was induced by replacing saline with 0.25% acetic acid (AA) to irritate the bladder. PNS was applied at multiple threshold (T) intensities for inducing anal sphincter twitching. During saline infusion, PNS at 2T and 4T significantly (P < 0.01) increased bladder capacity to 184.7 ± 12.6% and 214.5 ± 10.4% of the control capacity. Propranolol (3 mg/kg iv) had no effect on PNS inhibition, but 3-[(2-methyl-4-thiazolyl)ethynyl]pyridine (MTEP; 1-3 mg/kg iv) significantly (P < 0.05) reduced the inhibition. During AA irritation, the control bladder capacity was significantly (P < 0.05) reduced to ∼22% of the saline control capacity. PNS at 2T and 4T significantly (P < 0.01) increased bladder capacity to 406.8 ± 47% and 415.8 ± 46% of the AA control capacity. Propranolol significantly (P < 0.05) reduced the bladder capacity to 276.3% ± 53.2% (at 2T PNS) and 266.5 ± 72.4% (at 4T PNS) of the AA control capacity, whereas MTEP (a metabotropic glutamate 5 receptor antagonist) removed the residual PNS inhibition. Bilateral transection of the hypogastric nerves produced an effect similar to that produced by propranolol. This study indicates that hypogastric nerves and a ß-adrenergic mechanism in the detrusor play an important role in PNS inhibition of nociceptive but not non-nociceptive reflex bladder activity. In addition to this peripheral mechanism, a central nervous system mechanism involving metabotropic glutamate 5 receptors also has a role in PNS inhibition.

Pudendal but not tibial nerve stimulation inhibits bladder contractions induced by stimulation of pontine micturition center in cats.

This study examined the possibility that pudendal nerve stimulation (PNS) or tibial nerve stimulation (TNS) inhibits the excitatory pathway from the pontine micturition center (PMC) to the urinary bladder. In decerebrate cats under α-chloralose anesthesia, electrical stimulation of the PMC (40 Hz frequency, 0.2-ms pulse width, 10-25 s duration) using a microelectrode induced bladder contractions >20 cmH2O amplitude when the bladder was filled to 60-70% capacity. PNS or TNS (5 Hz, 0.2 ms) at two and four times the threshold (2T and 4T) to induce anal or toe twitch was applied to inhibit the PMC stimulation-induced bladder contractions. Propranolol, a nonselective ß-adrenergic receptor antagonist, was administered intravenously (1 mg/kg i.v.) to determine the role of sympathetic pathways in PNS/TNS inhibition. PNS at both 2T and 4T significantly (P < 0.05) reduced the amplitude and area under the curve of the bladder contractions induced by PMC stimulation, while TNS at 4T facilitated the bladder contractions. Propranolol completely eliminated PNS inhibition and TNS facilitation. This study indicates that PNS, but not TNS, inhibits PMC stimulation-induced bladder contractions via a ß-adrenergic mechanism that may occur in the detrusor muscle as a result of reflex activity in lumbar sympathetic nerves. Neither PNS nor TNS activated a central inhibitory pathway with synaptic connections to the sacral parasympathetic neurons that innervate the bladder. Understanding the site of action involved in bladder neuromodulation is important for developing new therapies for bladder disorders.

Corneal blindness and xenotransplantation.

Approximately 39 million people are blind worldwide, with an estimated 285 million visually impaired. The developing world shoulders 90% of the world's blindness, with 80% of causative diseases being preventable or treatable. Blindness has a major detrimental impact on the patient, community, and healthcare spending. Corneal diseases are significant causes of blindness, affecting at least 4 million people worldwide. The prevalence of corneal disease varies between parts of the world. Trachoma, for instance, is the second leading cause of blindness in Africa, after cataracts, but is rarely found today in developed nations. When preventive strategies have failed, corneal transplantation is the most effective treatment for advanced corneal disease. The major surgical techniques for corneal transplantation include penetrating keratoplasty (PK), anterior lamellar keratoplasty, and endothelial keratoplasty (EK). Indications for corneal transplantation vary between countries, with Fuchs' dystrophy being the leading indication in the USA and keratoconus in Australia. With the exception of the USA, where EK will soon overtake PK as the most common surgical procedure, PK is the overwhelming procedure of choice. Success using corneal grafts in developing nations, such as Nepal, demonstrates the feasibility of corneal transplantation on a global scale. The number of suitable corneas from deceased human donors that becomes available will never be sufficient, and so research into various alternatives, for example stem cells, amniotic membrane transplantation, synthetic and biosynthetic corneas, and xenotransplantation, is progressing. While each of these has potential, we suggest that xenotransplantation holds the greatest potential for a corneal replacement. With the increasing availability of genetically engineered pigs, pig corneas may alleviate the global shortage of corneas in the near future.

Reductions of aldehydes and ketones with a readily available N-heterocyclic carbene borane and acetic acid.

Acetic acid promotes the reduction of aldehydes and ketones by the readily available N-heterocyclic carbene borane, 1,3-dimethylimidazol-2-ylidene borane. Aldehydes are reduced over 1-24 h at room temperature with 1 equiv of acetic acid and 0.5 equiv of the NHC-borane. Ketone reductions are slower but can be accelerated by using 5 equiv of acetic acid. Aldehydes can be selectively reduced in the presence of ketones. On a small scale, products are isolated by evaporation of the reaction mixture and direct chromatography.

[3 + 2]-dipolar cycloaddition reactions of an N-heterocyclic carbene boryl azide.

Thermal 1,3-dipolar cycloaddition reactions of 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene dihydridoboron azide occur smoothly with alkynes, nitriles, and alkenes bearing electron-withdrawing groups. New, stable NHC-boryl-substituted triazoles, tetrazoles, and triazolidines are formed in good to excellent yields.