Cajal Cell Counts are Important Predictors of Outcomes in Drug Refractory Gastroparesis Patients With Neurostimulation.

BACKGROUND AND AIMS: Cajal cells serve as the pacemaker cells of the gastrointestinal tract and regulates peristalsis. On the baisis of that fact, it has been hypothesized that a decrease in Cajal cells can lead to gastroparesis and other motility issues. Treatment with medications has a limited efficacy and most resort to gastric electrical stimulation (GES) devices for symptomatic relief. We believe that the number of Cajal cells present is directly proportional to symptomatic relief with GES. MATERIALS AND METHODS: Twenty-three (white female) subjects were recruited from the gastric motility clinic University of Mississipi for this study with the criteria of drug refractory gastropersis. Symptoms were measured using Likert scale and gastric emptying times were measured pre-GES and post-GES. Serosal electrogram measurements were recorded during surgical placement of permanent electrical stimulator under various modes. Cajal cell count scoring via immunohistochemistry were performed during the implantaion of the GES. RESULTS: The data were grouped in 2 categories based on the Cajal cells that is ≥2.00 and <2.00. Subjects with higher Cajal cells reported a statiscially improvement in gastroperesis symptoms. Significant differences were also noted in the first hour gastric emptying study. The mean group difference is 17.5 (95% confidence interval, 1.41-33.58; P=0.035). Serosal amplitude differences were noted being significantly higher in the group with ≥2 cajal cells. CONCLUSIONS: Electrograms obtained after GES demonstrates immediate improvement in gastric electrical activity and gastroparesis symptoms in patients with relatively higher Cajal cell counts when compared with patients with extensive loss of Cajal cells.

Gastric Electrical Stimulation Is an Option for Patients with Refractory Cyclic Vomiting Syndrome.

BACKGROUND/AIMS: Cyclic vomiting syndrome (CVS) is a disabling migraine variant manifesting as severe episodes of nausea and vomiting and often refractory to many therapies. Gastric electrical stimulation (GES), which can reduce nausea and vomiting in gastroparesis, may provide symptomatic relief for drug-refractory CVS. This study assessed the utility GES in reducing the symptoms of CVS and improving the quality of life. METHODS: A one-year, non-randomized, clinical study was conducted. Eleven consecutive patients with drug refractory, cyclic vomiting syndrome based on Rome III criteria and North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN), underwent treatment with temporary GES (Temp GES) and permanent GES (Perm GES). Post-treatment follow up was done up to one year after permanent gastric electrical stimulation therapy. RESULTS: Total symptom score decreased by 68% and 40% after temporary and permanent GES therapies, respectively. Hospital admission events significantly decreased to 1.50 (± 1.00) events from 9.14 (± 7.21) annual admissions prior to treatment with permanent GES. Vomiting episodes fell by 83% post Temp GES and 69% after Perm GES treatments. Mucosal electrogram values also changed after temporary stimulation. CONCLUSIONS: In a small group of drug-refractory CVS patients, treatments with temporary and permanent GES significantly reduced the severity of gastrointestinal symptoms and frequency of hospital admissions.

Gastric Electrical Stimulation and Sacral Electrical Stimulation: A Long-Term Follow-Up Study of Dual-Device Treatment.

AIMS: The objective of this study was to investigate sacral electrical stimulation (SES) and gastric electrical stimulation (GES) by comparing upper and lower gastrointestinal (GI) and genitourinary (GU) symptoms and quality of life, before treatment and in the long term after treatment. We hypothesized that dual-device treatment would greatly improve upper and lower gastrointestinal and genitourinary symptoms, as well as quality of life. METHODS: Fifty-four patients who underwent dual-device treatment (GES and SES) were enrolled in this study. Patients who had surpassed 24 months since the second-device insertion were included. Patients were evaluated before and after both devices were implanted and given a symptom questionnaire regarding their upper GI, lower GI, and GU symptoms and their quality of life. RESULTS: With combined treatment, a statistically significant improvement was seen in upper GI, lower GI, and GU symptoms and quality of life. However, fecal incontinence and fecal urgency improvements did not reach statistical significance, likely due to the small sample size. CONCLUSION: The implantation of two stimulators appears to be safe and effective to improve patients' quality of life for those with upper GI symptoms, bowel problems, and bladder dysfunction.

Management of complicated chronic anal fissures with high-dose circumferential chemodenervation (HDCC) of the internal anal sphincter.

BACKGROUND: Botulinum toxin injection into the internal anal sphincter (IAS) is gaining popularity as a second line therapy for chronic anal fissures after patients fail medical therapy. The dosage of Botulinum toxin reported in the literature ranged from 20 to 50 IU. Complicated chronic anal fissure is defined as persistent fissure concurrent with other perianal pathology. We report a new approach involving high-dose circumferential chemodenervation (HDCC) of 100 IU in treating these complicated chronic anal fissures. AIM: The aim of this study was to evaluate the fissure healing, complication, and recurrence rates with HDCC. METHODS: Complicated anal fissure was defined as fissure with other perianal pathologies including skin tag, hypertrophied papilla, fistula, symptomatic hemorrhoids, anal condylomata, and abscess. Between 2008 and 2012, 62 consecutive patients (28 Blacks, 33 Whites, 1 Hispanic) with complete follow-up data were included in this single arm study. These patients underwent HDCC-IAS with addition interventions by a single colorectal surgeon. Follow up data were obtained by chart review and office follow up. RESULTS: Of the 62 patients, the overall success rate was greater than 70% at 3 months follow-up. A few patients developed transient flatus or fecal incontinence, but shortly resolved. There was no major complication following HDCC-IAS. CONCLUSIONS: Combination therapy involving HDCC-IAS and local anorectal surgery for associated condition is both safe and effective for fissure healing.

High-dose circumferential chemodenervation of the internal anal sphincter: A new treatment modality for uncomplicated chronic anal fissure: A retrospective cohort study (with video).

BACKGROUND: Botulinum toxin injection into the internal anal sphincter is gaining popularity as a second line therapy for chronic anal fissures if medical therapy fails. The dosage of botulinum toxin reported ranged from 20 to 50 IU with no more than 3 injection sites and results in a healing rate of 41%-88% at 3 months. We propose a new injection method of high-dose circumferential chemodenervation of 100 IU in treating chronic anal fissure. METHODS: This was a retrospective review at a single academic center. 75 patients (50 women and 25 men) with uncomplicated chronic anal fissures underwent high-dose circumferential chemodenervation-internal anal sphincter (100 IU). We measured fissure healing, complication, and recurrence rates at 3 and 6 months post injection. RESULTS: Of the 75 patients, healing rate was 90.7% at 3 months follow up with the first injection and 81.3% with the second injection. The recurrence rates were 20.6% and 12.5% at 6 months after the 1st and 2nd injections respectively. Excluding 5 patients who lost follow up, the total healing rate of the study cohort was 100%. At 2 weeks and 3 months, there were no major complications including hematoma, infection, flatus, fecal, and urinary incontinence. CONCLUSIONS: High-dose circumferential chemodenervation-internal anal sphincter (100 IU) is a safe and effective method for uncomplicated chronic anal fissure.

Evaluation and treatment of gastric stimulator failure in patients with gastroparesis.

OBJECTIVE: This study evaluates treatment of gastroparesis patients refractory to gastric electrical stimulation (GES) therapy with surgical replacement of the entire GES system. SUMMARY BACKGROUND DATA: Some patients who have symptomatic improvement with GES later develop recurrent symptoms. Some patients improve by simply altering pulse parameter settings. Others continue to have symptoms with maximized pulse parameters. For these patients, we have shown that surgical implantation of a new device and leads at a different gastric location will improve symptoms of gastroparesis. METHODS: This study evaluates 15 patients with recurrent symptoms after initial GES therapy who subsequently received a second GES system. Positive response to GES replacement therapy is evaluated by symptoms scores for vomiting, nausea, epigastric pain, early satiety, and bloating using a modified Likert score system, 0 to 4. RESULTS: Total symptom scores improved for 12 of 15 patients with GES replacement surgery. Total score for the replacement group decreased from 17.3 ± 1.6 to 13.6 ± 3.7 with a difference of 3.6 (P value = .017). This score is compared with that of the control group with a preoperative symptom score of 15.8 ± 3.6 and postoperative score of 12.3 ± 3.5 with a difference of 3.5 (P value = .011). The control group showed a 20.3% decrease in mean total symptoms score, whereas the study group showed a 22.5% decrease in mean with an absolute reduction of 2.2. CONCLUSION: Reimplantation of a GES at a new gastric location should be considered a viable option for patients who have initially failed GES therapy for gastroparesis.

Gastric electrical stimulation for abdominal pain in patients with symptoms of gastroparesis.

Abdominal pain physiology may be better understood studying electrophysiology, histology, and symptom scores in patients with the symptoms of gastroparesis (Gp) treated with gastric electrical stimulation (GES). Ninety-five Gp patients' symptoms were recorded at baseline and during temporary and permanent GES. Gastric-emptying times and cutaneous, mucosal, and serosal electrogastrograms were obtained. S100-stained, full-thickness gastric biopsies were compared with autopsy controls. Sixty-eight patients reported severe pain at baseline. Severe pain patients' mean pain scores decreased with temporary GES from 3.62 to 1.29 (P < 0.001) and nonsevere pain from 1.26 to 0.67 (P = 0.01). With permanent GES, severe mean pain scores fell to 2.30 (P < 0.001); nonsevere pain changed to 1.60 (P = 0.221). Mean follow-up was 275 days. Mean cutaneous, mucosal, and serosal frequencies and frequency-to-amplitude ratios were markedly higher than literature controls. For patients with Gp overall and subdivided by etiology and severity of pain, S-100 neuronal fibers were significantly reduced in both muscularis propria layers. GES improved severe pain associated with symptoms of Gp. This severe pain is associated with abnormal electrogastrographic activity and loss of S100 neuronal fibers in the stomach's inner and outer muscularis propria and, therefore, could be the result of gastric neuropathy.

Long-term effects of gastric stimulation on gastric electrical physiology.

INTRODUCTION: This study evaluates the modeling of gastric electrophysiology tracings during long-term gastric electrical stimulation for gastroparesis. We hypothesized that serosal electrogastrogram may change over time representing gastric remodeling from gastric stimulation. PATIENTS: Sixty-five patients with gastroparesis underwent placement of gastric stimulator for refractory symptoms. Mean age at initial stimulator placement was 44 years (range, 8-76), current mean age was 49, and the majority of the subjects were female (n = 51, 78 %). Only a minority had diabetes-induced gastroparesis (n = 16, 25 %); the remainder were either idiopathic or postsurgical. METHODS: At the time of stimulator placement, electrogastrogram was performed after the gastric leads were placed but before stimulation was begun. Patients underwent continuous stimulation until pacer batteries depleted. At the time of replacement, before the new pacemaker was attached, electrogastrogram was again performed. RESULTS: After a mean of 3.9 years of stimulation therapy, the mean of baseline frequency before stimulation therapy was 5.06 cycles/min and declined to 3.66 after replacement (p = 0.0000002). The mean amplitude was 0.33 mV before stimulation therapy and decreased to 0.31 mV (p = 0.73). The frequency/amplitude ratio was 38.4 before stimulation therapy and decreased to 21.9 (p = 0.001). CONCLUSION: Long-term gastric electrical stimulation causes improvement in basal unstimulated gastric frequency to near normal.

Simultaneous liver metastasectomy at operation for primary colorectal or gynecologic malignancy.

BACKGROUND: Treatment of synchronous resectable colorectal liver metastases has traditionally involved a staged surgical approach. Specialized centers have demonstrated good results with simultaneous resection. We aim to report our outcomes at the University of Mississippi Medical Center (UMMC) with simultaneous liver metastasectomy at the time of operation for primary colorectal or gynecologic malignancy STUDY DESIGN: From January 2010- September 2011, 6 patients underwent simultaneous resection of liver metastases and primary colorectal or gynecologic malignancy. Operative, postoperative, and pathologic data were retrospectively reviewed. RESULTS: Four patients with colorectal primaries underwent simultaneous resection. One received abdominoperineal resection with resection of lesions in hepatic segments II and VII. A second received right hemicolectomy with en bloc resection of gallbladder and segments IV and V. The third and fourth patients both underwent left colectomy with resection of segments IV and V, respectively. All resections were non-anatomic, and frozen-sections were confirmed to be negative at the resection base. No patients suffered additional postoperative morbidity or mortality related to liver resection. Two patients had ovarian cancer with metastatic disease to the liver. The first underwent en bloc resection ofgallbladder and segments IV and V along with extensive debulking. The second had recurrent ovarian cancer with metastases with liver segments VI and VII. Both patients underwent simultaneous resection with no added postoperative morbidity or mortality attributed to hepatic resection. For gynecologic malignancy, the objective is to remove bulky disease, and although microscopic margins were positive, the goal of tumor load reduction was achieved. CONCLUSIONS: Liver resection at the time of operation for primary colorectal or gynecologic malignancy can safely be performed with the benefit of avoiding morbidity of a second laparotomy without compromising safety.

Predictable closure of the abdominoperineal resection defect: a novel two-team approach.

BACKGROUND: Primary closure of the perineum at the time of abdominoperineal resection (APR) is seldom successful. Several factors are known to adversely affect healing, including neoadjuvant chemoradiation, tension, contamination, and fluid collection. This study evaluates a 2-team approach for resection and routine perineal closure in a single stage. STUDY DESIGN: After tumor resection, the abdominal and perineal closures are performed simultaneously by 2 separate teams. A competent closure of the perineal defect is achieved with bilateral V-to-Y inferior gluteal artery perforator fasciocutaneous flaps (BIGAP) mobilizing buttock skin, fat, and gluteal muscle fascia for inset into the defect. No muscle is elevated with the flaps and no attempt is made to obliterate the deepest aspects of the pelvic defect. RESULTS: Beginning in August 2010, 18 consecutive patients who underwent APR for distal rectal (n = 14) and anal carcinoma (n = 4) were included in the study. All patients had received neoadjuvant chemoradiation therapy. Primary healing was achieved in 16 of 18 patients with a completely tension-free closure. One patient required debridement and secondary closure. Another patient had an unresectable tumor, which invaded the flap closure. Minor healing problems were seen in 7 patients. CONCLUSIONS: BIGAP flaps provide sufficient tissue to predictably provide primary closure of the perineal defect. Perineal wound healing morbidity is dramatically reduced compared with primary simple closure of this defect. Early results indicate that this method of perineal closure offers a straightforward and predictable method that is comparable in efficacy to other methods using pedicled flaps for perineal closure.