Motility Disorders after Roux-en-Y Gastrojejunostomy

About 30% of patients who have a Roux-en-Y gastrojejunostomy after gastrectomy suffer from abdominal pain, nausea, vomiting of food and bloating made worse by eating. This syndrome, called the Roux stasis syndrome, is caused, in part, by a motility disorder of the Roux limb. Transection of the jejunum during the construction of the limb separates the limb from the natural small intestinal pacemaker located in the duodenum. Ectopic pacemakers then appear in the limb and trigger retrograde contractions in its proximal portion. These contractions slow transit through the limb and result in Roux stasis. Current nonsurgical treatment of the syndrome includes the use of prokinetic agents and intestinal pacing, neither of which has demonstrated long-term benefits. A near-total gastrectomy may speed upper gastrointestinal transit somewhat, but stasis in the Roux limb often persists. Our current approach aims at preventing the syndrome by the use of an ‘uncut’ Roux limb, an operation which preserves myoneural continuity between the duodenal pacemaker and the Roux limb and so prevents the appearance of ectopic pacemakers and stasis in the limb.     

Helicobacter pylori-induced diarrhea post-ileogastrostomy

A retrospective study of all ileogastrostomy procedures (n=26) performed in 1993 by one surgeon (IGMC) was carried out to investigate the hypothesis that Helicobacter pylori may be implicated in certain severe cases of postoperation nausea and diarrhea. Ten of 26 persons (38.5%) displayed nausea and notable diarrhea (greater than or equal to ten bowel movements per day), seven of which warranted upper GI investigation. One hundred per cent (seven of seven) of these persons were found to possess H. pylori upon C-14 breath test. In four of six cases eradication therapy (1 g amoxicillin b.i.d./20 mg omeprazole b.i.d. for 2 weeks) corresponded with a resolution of severe nausea and diarrhea (one additional case involved omeprazole use only), suggesting that H. pylori should be considered as a possible cause of these symptoms post-ileogastrostomy. Additionally, in four of seven cases persons were re-tested (C-14 breath analysis) at least 1 month post-therapy and in this group three persons were found to be free of the organism. All three cases of notable diarrhea and nausea resolved with treatment, providing the strongest evidence for a possible association between infection and these symptoms.     

Gallbladder Findings after Cholecystectomy in Morbidly Obese Patients

Morbidly obese patients constitute a high risk group for the development of gallbladder disease. In our series 70 consecutive patients underwent vertical gastroplasty in an effort to manage morbid obesity. The mean age was 37 years (range 20-60), and the mean excess body weight was 92 kg (range 52-265). Six patients (8.5%) had undergone cholecystectomy before bariatric surgery because of symptomatic cholelithiasis. The remaining 64 patients underwent cholecystectomy at the time of vertical gastroplasty. Ninety-seven percent of the removed gallbladders had gross or histologic abnormalities, including cholelithiasis 18.5% (13 patients), and cholesterolosis 31% (22 patients). Histologically, chronic cholecystitis was present in all patients with cholelithiasis and cholesterolosis. Chronic cholecystitis alone was found in 27 patients (38.5%) and only two patients (3%) had normal findings. The mean excess body weight of the patients with cholesterolosis (96 kg) was not significantly greater than that of patients with cholelithiasis (89 kg) or chronic cholecystitis (88 kg). Our findings suggest that cholecystectomy should be performed in all morbidly obese patients concomitant with vertical gastroplasty.     

Primary colorectal non-Hodgkin's lymphoma

Background: The gastrointestinal tract is the most common site of extranodal involvement in non-Hodgkin's lymphoma (NHL). Primary colorectal NHL comprises 13–18% of all gastrointestinal NHL but is not commonly reported as a separate entity. Methods: This was a retrospective review of the medical records of 19 patients over a 16-year period to evaluate the clinical features and behavior of colorectal NHL. Results: A pediatric group of seven male patients presented at an early stage with acute symptomatology. The primary tumor was located in the ileocecum in all cases and intussusception was common. An adult group of 12 patients presented at a later stage with chronic symptomatology. Staging study results were positive by bone marrow biopsy in four of 16 patients (25%), by lymphangiography in six of 11 patients (54.5%), and by gallium scan in eight of 10 patients (80%). Seven patients relapsed a median of 8 months after treatment. Three other patients died during treatment, one died of other causes, and one died without receiving treatment. The remaining seven patients are alive from 41 to 231 months without evidence of disease. Five of these patients are in the pediatric group, where the median survival was >72 months. The overall median survival was 45 months. Conclusion: Colorectal NHL is a disease that affects both the pediatric and adult population. Although pediatric patients have an excellent prognosis with anticipated long-term survival after treatment, long-term survival can be expected in 50% of adult patients. In both groups of patients, multimodality therapy with surgery, chemotherapy, and radiation is the treatment of choice.Presented at the 46th Annual Cancer Symposium of The Society of Surgical Oncology, Los Angeles, California, March 18–21, 1993.     

Selective attenuation of neuropeptide-Y-mediated contractile responses in blood vessels from patients with diabetes mellitus

Vascular smooth muscle contractile responses to neuropeptide Y, ,ß-methyleneATP and noradrenaline were studied in circular segments of isolated vessels with intact endotheliumin vitro from 12 patients with diabetes mellitus type 2 (NIDDM) and 12 control subjects. The dilatory effect of acetylcholine was used to test the function of the endothelium. Subcutaneous arteries and veins (diameter 0.1–1.1 mm) were obtained during surgery. There was no difference in contractile responses to noradrenaline or ,ß-methyleneATP between diabetic and control vessels. The contractile response to neuropeptide Y, however, was markedly reduced in the diabetic group. The maximal contractile effect (46.0 ± 14.0%,p < 0.05) but not the sensitivity to neuropeptide Y was significantly less in diabetic veins compared to control (107.5 ± 19.6%). Thus, the attenuation of neuropeptide Y responses was present in humans as previously observed in alloxan-induced diabetes mellitus in rabbits. There was no difference in the dilator effect of acetylcholine between the diabetic and the control group in any of the vessel types, indicating that the difference in vascular reactivity to neuropeptide Y was not endothelium-dependent. In conclusion, the present study has shown that the postjunctional effects of neuropeptide Y, a co-transmitter of the peripheral sympathetic nervous system, is selectively attenuated in diabetes mellitus.     

Comparison of autonomic function using Valsalva ratio and 30:15 postural ratio prior to and after haemodialysis treatment

In published studies of chronic haemodialysis patients, the frequency of autonomic dysfunction varies widely. One reason for the variation may be the time of testing with respect to time of dialysis. The current study tests the hypothesis that autonomic function — as measured by heart rate responses to the Valsalva manoeuvre (Valsalva ratio) and 30:15 electrocardiogram (ECG) R—R interval to upright posture (postural ratio) — is different when patients are above dry weight (predialysis) than when they are at or below dry weight (postdialysis). The study also reviews available literature to analyze other factors that may affect the results of autonomic testing in this population. A total of 25 chronic haemodialysis patients underwent standard Valsalva and 30:15 R—R interval postural autonomic testing prior to and after haemodialysis. In addition, pre- and postdialysis orthostatic responses were measured and compared with a control population. The 30:15 ratio increased after dialysis (p = 0.001). The Valsalva ratio did not change with dialysis. Out of 25 subjects, seven had an abnormal 30:15 ratio prior to dialysis decreasing to two out of 25 patients postdialysis (p < 0.03). Orthostatic responses predialysis did not differ from those in the control group. Review of the literature shows great variability in definition of normal Valsalva and postural (30:15 R—R interval) ratios. Diabetic patients in the current and prior studies were more likely to have abnormal responses. In conclusion, the prevalence of autonomic dysfunction in chronic dialysis patients as determined by Valsalva and 30:15 ECG postural ratios may be influenced by the following factors: when subjects are studied with respect to their dialysis treatment; the number of subjects with diabetes; and the cut-off point used to define abnormal test results. Abnormal Valsalva ratios are less frequent when measured postdialysis.     

Hyposensitivity of peripheral α-adrenoceptors in respiratordependent amyotrophic lateral sclerosis assessed by intravenous norepinephrine infusion

Intravenous norepinephrine infusion test was performed in eight patients with amyotrophic lateral sclerosis (ALS) supported by respirators and nine control subjects, to examine -adrenoceptor function of peripheral resistant blood vessels. Baseline plasma norepinephrine concentrations in ALS patients were significantly higher than those in control subjects, indicating basal sympathetic hyperactivity (normal 218.2 ± 59.7 pg/ml; ALS 450.0 ± 288.4 pg/ml). The stimulus-response curves in the patients were similar to those in control subjects, and there were no significant differences between mean gains of the stimulus—response curves in both groups (normal 18.7 ± 5.5; ALS 15.2 ± 11.2). However, three ALS patients, two of whom had circulatory fluctuation and sympathetic hyperactivity, revealed lower gain levels than the mean minus 2 SD in control subjects (4.7, 1.1 and 3.7). This indicates hyposensitivity or down-regulation of the -adrenoceptor function of peripheral blood vessels in these ALS patients. For early detection of sympathetic hyperactivity and prediction of circulatory collapse, it would be useful to measure the plasma norepinephrine concentration and the gain of the norepinephrine infusion curve in respirator-dependent ALS patients.     

Molecular genetic studies of early breast cancer evolution

Summary In the past few years there has been an explosion in the number of patients diagnosed with hyperplastic breast disease andin situ breast cancer. Based on epidemiological data, these morphologically defined lesions may be categorized as those with little malignant potential (e.g. typical hyperplasia or proliferative disease without atypia [PDWA]), those with significant malignant potential which may already be initiated (e.g. atypical ductal hyperplasia [ADH]), and early transformed lesions which are malignant but not yet invasive (e.g. ductal carcinomain situ [DCIS]). They may represent sequential evolutionary stages in the ontogeny of invasive breast cancer, with each morphologically defined stage resulting from accumulating genetic changes culminating in a transformed clonal lineage capable of invasion and metastasis. Using loss-of-heterozygosity (LOH) analysis, we are studying the genetic changes associated with these lesions in archival tissue samples. 50% (6/12) of the proliferative lesions (PDWA and ADH) and 80% of the DCIS shared their LOH patterns with more advanced lesions from the same breast, strongly supporting a precursor/product relationship between these lesions and the cancers they accompany.     

Measurement of gastric and duodenal mucosal protein turnover in humans

Conventional measurement of mucosal turnover is based on labeling cellular DNA with [³H]thymidine, but because of the risk of genetic damage, this technique is not suitable for studies in normal human subjects. Consequently, we have measured mucosal protein turnover by a primed/continuous intravenous infusion of tracer quantities of [1¹⁴C]leucine and measured its incorporation into mucosal protein at 4 hr in nine healthy adult volunteers. Mucosal samples were obtained by standard endoscopic techniques from the distal duodenum and gastric antrum. In addition, duodenal villous height and width were measured by microscopic micrometric techniques in order to calculate villous growth rate. Results demonstrated a mucosal protein turnover of 57±5%/day in gastric antrum and 39±2%/day in duodenum, suggesting a mucosal replacement rate of 1.8 and 2.6 days, respectively. Average duodenal villous height was 433±77 m, suggesting a villous growth rate of approximately 160 m/day. As our mucosal protein turnover rates are similar to epithelial turnover rates measured by cellular labeling techniques, our results support the intestinal proliferon theory that suggests all mucosal elements follow similar turnover characteristics. In conclusion, the technique should provide a practical alternative method of studying the effect of disease upon mucosal regeneration and repair.