Timothy J. Ridolfi

Effects of autonomic nerve stimulation on colorectal motility in rats

Background  Several disease processes of the colon and rectum, including constipation and incontinence, have been associated with abnormalities of the autonomic nervous system. However, the autonomic innervation to the colon and rectum are not fully understood. The aims of this study were to investigate the effect of stimulation of vagus nerves, pelvic nerves (PN) and hypogastric nerves (HGN) on colorectal motility in rats.

Exogenous stem cell factor improves interstitial cells of Cajal restoration after blockade of c-kit signaling pathway.

Abstract Objective. Interstitial cells of Cajal (ICC) have been endowed with considerable intrinsic plasticity. Blockade of the c-kit signaling pathway results in the shift of ICC towards a smooth muscle-like phenotype. Little is known about stem cell factor (SCF), the ligand of c-kit, and the role it plays in the process of restoration. The aim of this study was to determine whether exogenous SCF can promote ICC replenishment following the blockade of c-kit signaling. Material and methods. Neutralizing anti-c-kit monoclonal antibody (ACK2) was administered to mice for 8 days after birth. Jejunal muscle strips were cultured up to 7 days. Electrical rhythmic changes were monitored and ICC were examined by immunohistochemistry. Expression of c-kit mRNA was detected by reverse transcriptase-polymerase chain reaction, and expression of Kit protein was detected by Western blot. Results. When c-kit receptors were blocked, ICC nearly disappeared from the jejunum accompanied by the loss of electrical slow waves. By day 7, after in vitro culture with SCF (100 ng/ml), the amplitude of muscle strip slow waves was restored to 0.19 ± 0.07 mV (p < 0.05), whereas the frequency recovered to 13.7 ± 3.32/min (p < 0.01). Furthermore, labeling for c-kit+ cells in the myenteric plexus increased and c-kit mRNA and protein expression were up-regulated compared to that of non-treatment with SCF. Conclusions. The c-kit signaling pathway, activated by SCF, is the critical pathway associated with the control of ICC survival and proliferation. The restoration of ICC number and jejunal electrical rhythm, resulting from blockade of the c-kit signaling pathway, could be facilitated by local SCF administration.

Achieving a complete colonic evaluation in patients with incomplete colonoscopy is worth the effort.

BACKGROUND: Patients with an incomplete colonoscopy are potentially at risk for missed lesions. OBJECTIVE: The purpose of this work was to identify the percentage of patients completing colonic evaluation after incomplete colonoscopy, the manner in which the evaluation was completed, and the incidence of significant pathology. DESIGN: This was a retrospective analysis of prospectively collected data. SETTINGS: The study was conducted in an outpatient colonoscopy clinic in the colorectal surgery department of a tertiary referral center. PATIENTS: Patients included those undergoing incomplete colonoscopy from a database of 25,645 colonoscopies performed from 1982 to 2009. INTERVENTIONS: Procedures aimed at completing colorectal evaluation were included in the study. MAIN OUTCOME MEASURES: Reason for incompletion, secondary study, its success, and findings were measured. RESULTS: A total of 242 patients with incomplete colonoscopies were identified; 166 (69%) were women. The average age of patients was 59 years. Most frequent causes for incomplete colonoscopy were inadequate preparation (34%), pain (30%), and tortuosity (20%). The scope could not pass the splenic flexure in 165 patients (71%). A total of 218 patients (90%) were offered completion studies, and 179 patients (82%) complied. Seventy-three of 82 patients who had a surveillance colonoscopy had a follow-up (89%), compared with 72 (87%) of 83 with symptoms and 40 (74%) of 54 who had a screening. Barium enema (BE) was performed in 74 (41%), repeat colonoscopy in 71 (40%), CT colonography in 17 (9%), and colonoscopy under general anesthesia in 9 patients (5%). Resection with intraoperative/perioperative colonoscopy was required in 8 patients (4%). Repeat colonoscopy found 32 lesions (24 tubular adenomas, 4 tubulovillous adenomas, and 4 sessile serrated polyps) in 17 patients (24%). Radiology demonstrated new abnormalities in 11 (12%) of 91 patients, prompting 7 colonoscopies. In 3 patients, colonoscopy showed an inverted appendix, a tubulovillous adenoma, and a sigmoid stricture. Overall, clinically significant lesions were found in 19 patients (10%). LIMITATIONS: This study was limited by an incomplete colonoscopy subjectively determined at the time of colonoscopy, as well as by a lack of comparison group. CONCLUSIONS: Complete colonic evaluation in patients with an incomplete colonoscopy is important. Repeat colonoscopy may be the most efficient way to achieve this.

A Case Study in Intra-abdominal Sepsis

Intra-abdominal infections are a common problem for the general surgeon and major sources of morbidity and mortality in the intensive care unit. Some of these patients present with peritonitis that can rapidly progress to septic shock. The basic principles of care include prompt resuscitation, antibiotics, and source control. This article will use a detailed case study to outline the management of a patient with severe intra-abdominal infection from diverticulitis from initial resuscitation to reconstruction. Components of the Surviving Sepsis Campaign as they pertain to surgical patients are discussed and updated, and the concept of damage control general surgery is applied.

The Role of 5-HT3 and 5-HT4 Receptors in the Adaptive Mechanism of Colonic Transit Following the Parasympathetic Denervation in Rats

BACKGROUND Clinical studies show that disturbed colonic motility induced by extrinsic nerves damage is restored over time. We studied whether 5-HT3 and 5HT4 receptors are involved in mediating the adaptive mechanisms following parasympathetic denervation. METHODS Parasympathetic denervation of the entire colon was achieved by bilateral pelvic nerve transection and truncal vagotomy in rats. Colonic transit was measured by calculating the geometric center (GC) of 51Cr distribution. Expression of 5-HT3 and 5HT4 receptor mRNA was determined by real time RT-PCR. RESULTS Parasympathetic denervation caused a significant delay in colonic transit (GC=4.36) at postoperative day (POD) 1, compared with sham operation (GC=6.31). Delayed transit was gradually restored by POD 7 (GC=5.99) after the denervation. Restored colonic transit was antagonized by the administration of 5-HT3 and 5HT4 receptors antagonists at POD 7. 5-HT3 and 5HT4 receptors mRNA expression were significantly increased in the mucosal/submucosal layer at POD 3 or POD 7, whereas no significant difference was observed in the longitudinal muscle layers adherent with the myenteric plexus (LMMP). CONCLUSIONS It is suggested that up-regulation of 5-HT3 and 5-HT4 receptors expression in the mucosal/submucosal layer is involved to restore the delayed transit after the parasympathetic denervation in rats.

Recovery of colonic transit following extrinsic nerve damage in rats

Abstract Introduction. Injury to pelvic sympathetic and parasympathetic nerves from surgical and obstetrical trauma has long been cited as a cause for abnormal colorectal motility in humans. Using a rat model, acute transaction of these extrinsic nerves has been shown to effect colorectal motility. The aim of this study is to determine in a rat model how transection of these extrinsic nerves affects colonic transit over time. Methods. Eighty-two Sprague–Dawley rats underwent placement of a tunneled catheter into the proximal colon. Bilateral hypogastric, pelvic nerves (HGN and PN) or both were transected in 66 rats. The remaining 16 rats received a sham operation. Colonic transit was evaluated at postoperative days (PODs) 1, 3, and 7 by injecting and calculating the geometric center (GC) of the distribution of 51Cr after 3 h of propagation. Results. At POD 1, transection of PNs significantly delayed colonic transit (GC = 4.9, p < 0.05), while transection of HGNs (GC = 8.5, p < 0.05) or transection of both nerves (GC = 7.8, p < 0.05) significantly accelerated colonic transit, when compared with sham operation (GC = 6.0). A significant trend toward recovery was noted in both the HGN and PN transection groups at POD 7. Conclusions. Damage to the extrinsic sympathetic and/or parasympathetic PNs affects colonic transit acutely. These changes in large bowel motor function normalize over time implicating a compensatory mechanism within the bowel itself.

Low Anterior Resection Syndrome: Current Management and Future Directions

Outcomes for rectal cancer surgery have improved significantly over the past 20 years with increasing rates of survival and recurrence, specifically local recurrence. These gains have been realized during a period of time in which there has been an increasing emphasis on sphincter preservation. As we have become increasingly aggressive in avoiding resection of the anus, we have begun accepting bowel dysfunction as a normal outcome. Low anterior resection syndrome, defined as a constellation of symptoms including incontinence, frequency, urgency, or feelings of incomplete emptying, has a significant impact on quality of life and results in many patients opting for a permanent colostomy to avoid these symptoms. In this article, we will highlight the most recent clinical and basic science research on this topic and discuss areas of future investigation.

Delayed gastrointestinal recovery after abdominal operation – role of alvimopan

Postoperative Ileus (POI), which occurs after surgical manipulation of the bowel during abdominal operations, is associated with prolonged hospital stay, increasing medical costs, and delayed advancement of enteral diet, which contributes to a significant economic burden on the healthcare system. The use of accelerated care pathways has shown to positively impact gut function, but inevitable postoperative opioid use contributes to POI. Alvimopan is a peripherally acting μ-opioid receptor antagonist designed to mitigate antimotility effects of opioids. In our review, we examined ten trials on alvimopan’s use after abdominal operations. Several of the earlier studies on patients undergoing bowel resection showed correlations between the study group and GI recovery as defined by passage of flatus, first bowel movement, and time to readiness for discharge. Data in patients undergoing total abdominal hysterectomy showed similarly decreased GI recovery time. Additionally, data within the past few years shows alvimopan is associated with more rapid GI recovery time in patients undergoing radical cystectomy. Based on our review, use of alvimopan remains a safe and potentially cost-effective means of reducing POI in patients following open GI surgery, radical cystectomy, and total abdominal hysterectomy, and should be employed following these abdominal operations.

Loop Ileostomy Closure as an Overnight Procedure: Institutional Comparison With the National Surgical Quality Improvement Project Data Set

BACKGROUND: Enhanced recovery pathways have decreased length of stay after colorectal surgery. Loop ileostomy closure remains a challenge, because patients experience high readmission rates, and validation of enhanced recovery pathways has not been demonstrated. This study examined a protocol whereby patients were discharged on the first postoperative day and instructed to advance their diet at home with close telephone follow-up. OBJECTIVE: The hypothesis was that patients can be safely discharged the day after loop closure, leading to shorter length of stay without increased rates of readmission or complications. DESIGN: Patients undergoing loop ileostomy closure were queried from the American College of Surgeons National Surgical Quality Improvement Project and compared with a single institution (2012–2015). Length of stay, 30-day readmission, and 30-day morbidity data were analyzed. SETTINGS: The study was conducted at a tertiary university department. PATIENTS: The study includes 1602 patients: 1517 from the National Surgical Quality Improvement Project database and 85 from a single institution. MAIN OUTCOME MEASURES: Length of stay and readmission rates were measured. RESULTS: Median length of stay was less at the single institution compared with control (2 vs 4 d; p < 0.001). Thirty-day readmission (15.3% vs 10.4%; p = 0.15) and overall 30-day complications (15.3% vs 16.7%; p = 0.73) were similar between cohorts. Estimated adjusted length of stay was less in the single institution (2.93 vs 5.58 d; p < 0.0001). There was no difference in the odds of readmission (p = 0.22). LIMITATIONS: The main limitations of this study include its retrospective nature and limitations of the National Surgical Quality Improvement Program database. CONCLUSIONS: Next-day discharge with protocoled diet advancement and telephone follow-up is acceptable after loop ileostomy closure. Patients can benefit from decreased length of stay without an increase in readmission or complications. This has the potential to change the practice of postoperative management of loop ileostomy closure, as well as to decrease cost. See Video Abstract at http://links.lww.com/DCR/A310.

Upregulation of mucosal 5‐HT3 receptors is involved in restoration of colonic transit after pelvic nerve transection

Background  Colonic dysfunction occurs after pelvic autonomic nerve damage. The enteric nervous system can compensate. We investigated the role of mucosal serotonin receptors, 5‐HT3 and 5‐HT4, in the colonic motility restoration over 2 weeks after parasympathetic pelvic nerve transection in a rat model.