Treating an oft-unrecognized and troublesome entity: using gastric electrical stimulation to reduce symptoms of malignancy-associated gastroparesis.

PURPOSE: Malignancy-associated gastroparesis (MAG) is a cause of morbidity in cancer patients but therapies are lacking. Gastric electrical stimulation (GES) is a novel treatment for MAG. Here, we describe 19 patients with MAG who underwent temporary GES placement. PATIENTS AND METHODS: Nineteen patients (6 males, 13 females) with various malignancies were reviewed for symptom scores and physiologic measures at baseline and after temporary GES placement. Symptoms were scored by three variables: nausea (N), vomiting (V), and GI total symptom score (TSS). Physiologic profiles were measured by solid and liquid phase gastric emptying scans (GET) at 1, 2, and 4 h and cutaneous electrogastrogram (EGG) and mucosal electrogram (EG) frequencies. Symptoms were measured for 5 days after temporary endoscopic GES placement, and measures were repeated post GES placement. RESULTS: Baseline GET results displayed delayed gastric emptying in 16 of 19 patients (mean solid retention 21.7 % at 4 h, normal <10 %; mean liquid retention 10.4 % at 4 h, normal <5 %). Cutaneous EGG (mean frequency 5.5 cpm) and EG (mean proximal frequency 5.1 cpm; mean distal frequency 5.1 cpm) showed evidence of neuromuscular dysfunction (normal 2.5-3.3 cpm). Symptom scores in N, V, and TSS showed statistically significant reduction after GES placement. CONCLUSION: A small sample of patients with MAG and receiving temporary GES experienced symptom improvement, with less change on gastric emptying time or gastric electrical amplitude or frequency. GES may provide a potential therapeutic option for symptomatic management of MAG and evaluation of these MAG patients after permanent GES placement is ongoing. Prospective studies of MAG using temporary and permanent GES may be warranted.

Temporary Endoscopic Stimulation in Gastroparesis-like Syndrome.

BACKGROUND/AIMS: Gastroparesis-like syndrome (GLS) is defined as gastroparesis-like symptoms with normal gastric scintigraphy. While the efficacy of gastric electrical stimulation (GES) in gastroparesis is well known, the utility of GES in GLS is largely unknown. Our aim was to clarify the role of GES in GLS. We implanted consecutive patients with symptoms of gastroparesis with temporary gastric electrical stimulation and observed changes in gastric scintigraphy and total symptom score. METHODS: Five hundred and fifty-one patients suffering from symptoms of gastroparesis (nausea, vomiting, bloating/distension, anorexia/early satiety, and abdominal pain) with negative endoscopy underwent gastric scintigraphy with analysis of 1) solid radionuclide gastric emptying at 1, 2, and 4 hours (% remaining); 2) area under the gastric emptying curve (AUC) at 1, 2, and 4 hours; and 3) total gastric emptying test (GET) (the sum of 1, 2, and 4 hour values). Patients were stratified into: delayed gastric emptying, normal gastric emptying, and rapid gastric emptying (Appendix). Of the 551 patients in the larger cohort, 379 had implantation of temporary gastric electrical stimulation (tGES). Gastrointestinal symptoms and gastric emptying were com - pared pre and post tGES implantation. RESULTS: After tGES, 2 hour gastric retention decreased (P < 0.01) for the delayed patients, and increased (P < 0.001) for normal and rapid patients. These changes were accompanied by improvements (P < 0.001) in vomiting, nausea, and total symptom scores in all 3 subgroups. CONCLUSIONS: Gastric electrical stimulation may be an effective therapy for treating the symptoms of gastroparesis with normal gastric emptying. Further exploration of endoscopic electrical stimulation as a treatment for gastroparesis-like symptoms with non-delayed gastric emptying is needed.

Arsenite disrupts mitosis and induces apoptosis in SV40-transformed human skin fibroblasts.

Chronic ingestion of arsenite-contaminated drinking water causes skin, bladder, and liver cancer. The mechanism of arsenite-induced carcinogenesis is unknown. Arsenite is known to disrupt mitosis and to delay transit through M phase in normal diploid fibroblasts. SV40-transformed human fibroblasts were observed to be hypersensitive to the cytotoxic and cytostatic effects of NaAsO(2) compared with normal diploid fibroblasts in concentration-response experiments. Five to 20 microM NaAsO(2) induced cytostasis in cycling normal diploid fibroblasts but not overt lethality in quiescent normal diploid fibroblasts. High concentrations of arsenite were overtly lethal in both cycling and quiescent cells. The IC50 for cycling SV40-transformed fibroblasts was 3.8 and 4.8 microM for the SV40-transformed lines GM4429 and GM0637, respectively, whereas, in cycling normal diploid fibroblasts (GM0024), the IC50 was 24.7 microM. Microscopic examination of NaAsO(2)-treated SV40-transformed fibroblasts suggested a concentration-dependent accumulation of cells in mitosis undergoing apoptosis. Treatment of SV40-transformed fibroblasts with 0-10 microM NaAsO(2) caused a concentration-dependent inhibition of cell proliferation, accumulation of cells having G2/M DNA contents, and increases in the mitotic index. Phase microscopy, annexin V binding, and electron microscopy demonstrated that arrested mitotic cells underwent apoptosis. These results indicate that SV40-transformation sensitizes cells to arsenite-induced mitotic arrest and induction of apoptosis in the mitotic cells.