Background & Aims Chronic unexplained nausea and vomiting (CUNV) is a debilitating disease of unknown cause. Symptoms of CUNV substantially overlap with those of gastroparesis, so the diseases therefore may share pathophysiologic features. We investigated this hypothesis by quantifying densities of interstitial cells of Cajal (ICCs) and mapping slow wave abnormalities in patients with CUNV vs controls. Methods Clinical data and gastric biopsy specimens were collected from 9 consecutive patients with at least 6 months of continuous symptoms of CUNV, but normal gastric emptying, treated at the University of Mississippi Medical Center, and from 9 controls (individuals undergoing bariatric surgery but free of gastrointestinal disease or diabetes). ICCs were counted and ultrastructural analyses were performed on tissue samples. Slow-wave propagation profiles were defined by high-resolution electrical mapping (256 electrodes; 36 cm2). Results from patients with CUNV were compared to those of controls as well as patients with gastroparesis who were previously studied by identical methods. Results Patients with CUNV had fewer ICCs than controls (mean 3.5 vs 5.6 bodies/field; P<.05), with mild ultrastructural abnormalities in the remaining ICCs. Slow-wave dysrhythmias were identified in all 9 subjects with CUNV vs only 1/9 controls. Dysrhythmias included abnormalities of initiation (stable ectopic pacemakers, unstable focal activities) and conduction (retrograde propagation, wave front collisions, conduction blocks, and re-entry), operating across bradygastric, normal (range 2.4−3.7 cycles/min), and tachygastric frequencies; dysrhythmias showed velocity anisotropy (mean 3.3 mm/s longitudinal vs 7.6 mm/s circumferential, P<.01). ICCs were less depleted in patients with CUNV than those with gastroparesis (mean 3.5 vs 2.3 bodies/field; P<.05), but slow-wave dysrhythmias were similar between groups. Conclusions This study defined cellular and bioelectrical abnormalities in patients with CUNV, including the identification of slow-wave re-entry. Pathophysiologic features of CUNV were observed to be similar to those of gastroparesis, indicating that they could be spectra of the same disorder. These findings offer new insights into the pathogenesis of CUNV and may help to inform future treatments.

A group of 97 patients with clinical stage I and stage II squamous carcinoma of the oral tongue, treated by partial glossectomy alone, has been reviewed to define prognostic indicators. Sixty-seven patients were staged T1N0 and 30 were T2N0. Disease recurred in 28 patients (27%) and the most common site of failure was the ipsilateral neck (21%). The incidence of initial recurrence did not vary significantly with patient age, sex, T-stage, or when tumor size was examined in other subdivisions. The presence of perineural invasion significantly increased recurrence rate (P = 0.003) and decreased survival (P = 0.002). Disease-free survival at 5 yr was 73% for patients with T1 tumors, and 62% for T2 tumors. This difference was not significant. In this low-risk patient population with early stage carcinoma of the oral tongue, partial glossectomy is adequate treatment in most cases. However, we recommend postoperative radiation therapy to the primary site and ipsilateral neck for patients with perineural invasion. No evidence could be found to support adjuvant local therapy or elective neck treatment in the remaining patients.

Background Gastric contractions are coordinated by slow waves, generated by interstitial cells of Cajal (ICC). Gastric surgery affects slow wave conduction, potentially contributing to post-operative gastric dysfunction. However, the impact of gastric cuts on slow waves has not been comprehensively evaluated. This study aimed to define consequences of surgical excisions on gastric slow waves by applying high-resolution (HR) electrical mapping and in-silico modeling. Methods Patients undergoing gastric stimulator implantation (n=10) underwent full-thickness stapled excisions (25×15 mm, distal corpus) for histological evaluation, enabling HR mapping (256 electrodes; 36cm2) over and adjacent to excisions. A biophysically-based in-silico model of bi-directionally coupled ICC networks was developed and applied to investigate the underlying conduction mechanisms and importance of excision orientation. Results Normal gastric slow waves propagated aborally (3.0±0.2 cycles/min). Excisions induced complete conduction block and wavelets that rotated around blocks, then propagated rapidly circumferentially distal to blocks (8.5±1.2 vs normal 3.6±0.4 mm s−1; p<0.01). This ‘conduction anisotropy’ homeostatically restored antegrade propagating gastric wavefronts distal to excisions. Excisions were associated with complex dysrhythmias in 5 patients: retrograde propagation (3/10), ectopics (3/10), functional blocks (2/10) and collisions (1/10). Simulations demonstrated conduction anisotropy emerged from bidirectional coupling within ICC layers and showed transverse incision length and orientation correlated to degree of conduction distortion. Conclusions Orienting incisions in the longitudinal gastric axis causes least disruption to electrical conduction and motility. However, if transverse incisions are made, a homeostatic mechanism of gastric conduction anisotropy compensates by restoring aborally-propagating wavefronts. Complex dysrhythmias accompanying excisions could modify post-operative recovery in susceptible patients.

A multifactorial analysis was used to identify the dominant prognostic variables predicting survival rates of 175 patients with hepatic metastases from colorectal carcinoma. Seven of 22 parameters examined simultaneously were found to independently influence the median survival rate in these patients: (1) elevated alkaline phosphatase (p = 0.0004), (2) elevated serum bilirubin level (p = 0.0005), (3) location of hepatic metastases (unilateral or bilateral, p = 0.0022), (4) number of metastatic nodes involved (0, 1-5, greater than 5; p = 0.0148), (5) depressed serum albumin (p = 0.0217), (6) whether or not the primary colorectal tumor was resected (p = 0.0013), and (7) chemotherapy (given or withheld, p = 0.0439). The prothrombin time, serum lactic dehydrogenase, and the number of hepatic metastases also correlated with survival, but they did not independently predict survival rates after other more dominant factors were accounted for. A mathematical equation for predicting an individual patient's clinical course once they developed hepatic metastases was derived from this statistical analysis. In addition, a simple and clinically useful guide for predicting outcome was developed that integrated the two most important risk factors, alkaline phosphatase and bilirubin.

Background Gastric electric stimulation (GES) at a high-frequency, low-energy setting is an option for treating refractory gastroparesis. The currently available commercial stimulator, the Enterra neurostimulator (Medtronic Inc, Minneapolis, MN), however, requires surgical implantation and is powered by a nonrechargeable battery. Objective To develop and test a miniature wireless GES device for endoscopic implantation in an experimental model. Design In-vivo gastric signals were recorded and measured in a nonsurvival swine model (n = 2; 110-lb animals). Intervention An endoscopically placed, wireless GES device was inserted into the stomach through an overtube; the two GES electrodes were endoscopically attached to the gastric mucosa and secured with endoclips to permit stimulation. Main Outcome Measurements Stable electrogastrogram measures were observed during GES stimulation. Results Electrogastrogram recordings demonstrated that gastric slow waves became more regular and of constant amplitudes when stomach tissues were stimulated, in comparison with no stimulation. The frequency-to-amplitude ratio also changed significantly with stimulation. Limitation Nonsurvival pig studies. Conclusion Gastric electric stimulation is feasible by our endoscopically implanted, wireless GES device.