Johannes Miholic

Emptying of the gastric substitute, glucagon-like peptide-1 (GLP-1), and reactive hypoglycemia after total gastrectomy

Postprandial glucagon-like peptide-1 (GLP-1), pancreatic glucagon, and insulin were measured in 27 tumor-free patients 43 months (median) after total gastrectomy and in four controls using a99technetium-labeled 100-g carbohydrate solid test meal. Emptying of the gastric substitute was measured by scintigraphy. Fourteen patients suffered from early dumping symptoms, and five of them also reported symptoms suggestive of reactive hypoglycemia (late dumping). The median emptying half-time (T1/2) of the gastric substitute was 480 sec. Sigstads dumping score was 8.5±1.6 (mean±se) in patients with rapid emptying (T1/2<480 sec), and 3.0±1.5 in patients with slow emptying of the gastric substitute (P=0.02). The peak postprandial concentration of GLP-1 was 44±20 pmol/liter in controls, 172±50 in patients without reactive hypoglycemia, and 502±116 in patients whose glucose fell below 3.8 mmol/liter during the second postprandial hour. Plasma GLP-1 concentrations peaked at 15 min, and insulin concentrations at 30 min after the end of the meal. A close correlation between integrated GLP-1 responses and integrated insulin responses (r=0.68) was observed. Multiple regression revealed that three factors were significantly associated with the integrated glucose concentrations during the second hour (60–120 min): Early (first 30 min) integrated GLP-1 (inverse correlation;P=0.006), age (P=0.006), and early integrated pancreatic glucagon (P=0.005). There was a close (inverse) relationship ofT1/2 with early integrated GLP-1 and pancreatic glucagon, but not with insulin. Gel filtration of pooled postprandial plasma of gastrectomized individuals revealed that all glucagon-like immunoreactivity eluted atKd 0.30 (Kd, coefficient of distribution), the elution position of glicentin. Almost all of the GLP-1 like immunoreactivity eluted atKd 0.60, the elution position of gut GLP-1. The authors contend that GLP-1-induced insulin release and inhibition of pancreatic glucagon both contribute to the reactive hypoglycemia encountered in some patients following gastric surgery. Rapid emptying seems to be one causative factor for the exaggerated GLP-1 release in these subjects.

Risk factors for severe bacterial infections after valve replacement and aortocoronary bypass operations: analysis of 246 cases by logistic regression

Risk factors for severe bacterial infections, that is, deep sternal wound infection, pneumonia, septicemia, and prosthetic valve endocarditis, were evaluated in 246 consecutive patients undergoing valve replacement (N = 84) or aortocoronary bypass operation (N = 162). Multiple logistic regression analysis was applied to determine the ability of putative risk factors to predict infection. The risk factors considered were age, sex, diabetes mellitus, duration of cardiopulmonary bypass (CPB), duration of operation, amount of blood restored on the day of operation, repeat thoracotomy for bleeding, intraaortic balloon pumping, reoperation, emergency operation, and the professional status of the surgeon. Severe infections occurred in similar frequency after valve replacement (8/84; 9.5%) and aortocoronary bypass (11/162; 6.8%). For patients who had a bypass procedure, repeat thoracotomy was the only factor significantly associated with infection (p = 0.0004). However, the classification analysis revealed that this variable alone is too unspecific for a reliable prediction. Univariate analysis indicated that restoration of more than 2,500 ml of blood (p = 0.0001), reoperation (p = 0.0821), duration of operation (p = 0.0061), duration of CPB (p = 0.0318), and intraaortic balloon pumping (p = 0.0281) were associated with infection following valve replacement. A model with three variables emerged from the multiple logistic regression: after correction for blood restoration, reoperation, and duration of CPB, no other variable was of additional predictive value. For patients who underwent valve replacement, the model performed well in predicting complications. The classification analysis revealed a high correspondence between observed and predicted instances of infection: it correctly predicted 75% of the patients with infection and 96% of those without infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic factors in adenocarcinoma of the cardia

BACKGROUND The optimal extent of resection for adenocarcinomas of the gastroesophageal junction is controversial. This study was conducted to examine whether the extent of resection is an independent prognostic factor in cardia cancer. METHODS The records and survival data of 125 patients who underwent resection for cancer of the cardia were retrospectively analyzed. Multiple regression was used to evaluate prognostic factors in patients who underwent proximal gastric resection (PR) or total gastrectomy (TG) for cancer of the cardia. RESULTS Seventy-five patients underwent PR and 50 TG. The 5-year survival was 40% for tumors confined to the esophageal wall (T1, T2), and 13% in more advanced cases (T1, T2; P = 0.0001). Twenty-two percent of the patients with tumor-free margins, 10% of those with microscopic residual tumor, and none with macroscopic residual tumor survived longer than 5 years (P = 0.0001 for any residual tumor versus no residual tumor). Lymph node involvement (P = 0.002) and stage (P = 0.0001) were also significant in the univariate analysis. Five-year survival was 18% after TG, and 17% after PR (P = NS). CONCLUSION Multiple regression identified residual tumor and penetration depth as independent predictors of survival (P = 0.0002, and P = 0.0001, respectively). After correction for these factors, none of the following variables were of additional significance: extent of resection (TG versus PR), lymph node involvement, age, or Laurens classification. In 19 of 20 cases with microscopic incomplete resection, it was the oral margin that was positive. We conclude that the extent of resection (TG versus PR) does not influence survival in adenocarcinoma of the gastroesophageal junction.

Emptying of the gastric substitute after total gastrectomy. Jejunal interposition versus Roux-y esophagojejunostomy.

Emptying of the gastric substitute and small bowel transit time of a 99mTc-labeled solid test meal were measured in 20 tumor-free patients 13 to 63 (median, 35) months after total gastrectomy with Roux-y (n = 11) and jejunal interposition (n = 9) reconstruction. The emptying half-times ranged from 2 minutes to greater than 20 minutes. Rapid emptying was associated with dumping symptoms (p less than 0.03) and shorter orocoecal transit-time (p less than 0.05). Serum glucose concentrations rose more quickly in jejunal interposition, but the areas under the curve were identical in both groups. The median insulin-to-glucose ratio (areas under the curve) during the 20 minutes after the meal was 11.4 in jejunal interposition and 7.1 in Roux-y esophagojejunostomy (NS). Interposition cases had regained a significantly higher percentage (89%) of their premorbid weight than patients with Roux-y (78%; p less than 0.05). The weight/height2 ratio was above the 50th centile in 45% of interpositions, but below the 50th centile in all patients after the Roux-y mode of reconstruction (p less than 0.05). It is concluded that the emptying velocity of the gastric substitute has no impact on postoperative weight gain. The authors contend that the concept of a gastric substitute pouch is not supported by the findings of this study.

Postprandial Release of Glucagon-Like Peptide-1, Pancreatic Glucagon, and Insulin after Esophageal Resection

Postprandial concentrations of glucose and the immunoreactivity of insulin, glucagon-like peptide-1 (GLP-1), and pancreatic glucagon were measured in 10 patients who had undergone esophageal resection (ER) and replacement by the stomach. Emptying of the esophageal substitute was assessed by scintigraphy using a 99Tc-labeled solid test meal. The data were compared with measurements performed in 14 controls, in 7 of whom gastric emptying was measured. The gastric emptying half time was 6.8 +/- 6.2 min (median 144 s) in ER cases, significantly shorter than in controls: 70 +/- 29 min (median 51 min). The early integrated (first 30 min) and total integrated insulin and GLP-1 concentrations were significantly higher than in controls. In 3 of 10 esophagectomy patients the blood glucose concentration fell below 3.8 mmol/l postprandially. High GLP-1 concentrations in the first 30 min were associated with low serum glucose during the 2nd h postprandially when all the hypoglycemic episodes occurred. It is concluded that rapid emptying of the esophageal substitute induces the exaggerated GLP-1 response, which is a main factor for reactive hypoglycemia.

Bone resorption is decreased postprandially by intestinal factors and glucagon-like peptide-2 is a possible candidate

Objective. Food intake inhibits bone resorption by a mechanism thought to involve gut hormones, and the intestinotrophic glucagon-like peptide 2 (GLP-2) is a candidate because exogenous GLP-2 inhibits bone resorption in humans. The purpose of the study was to investigate patients with short-bowel syndrome (SBS) or total gastrectomy in order to elucidate whether the signal for the meal-induced reduction of bone resorption is initiated from the stomach or the intestine. Material and methods. Bone resorption was assessed from the serum concentration of collagen type I C-telopeptide cross-links (s-CTX) and compared with the plasma concentrations of GLP-2. Bone formation was assessed from serum osteocalcin concentrations. Seven SBS patients with a preserved colon and 7 with SBS and colectomy and 7 healthy controls were given a breakfast test meal (936 kcal). Eight patients who had undergone total gastrectomy had an oral glucose load (75 g in 150 ml). Results. The SBS patients without a colon showed no reduction in bone resorption (s-CTX) to a meal, whereas SBS patients with a colon had an intermediate response with a 27% (p<0.05) reduction of s-CTX from baseline after 120 min as compared with 66% (p<0.001) for normal controls. A significant reduction of 53% (p<0.001) was seen in gastrectomized patients after receiving oral glucose, which is comparable with the published data for the oral glucose tolerance test (OGGT) in healthy subjects (50% reduction over 120 min). Bone formation was unchanged for both SBS and gastrectomy patients. GLP-2 concentrations increased significantly in all groups with the exception of the SBS plus colectomy group. Conclusions. An intestinal factor is responsible for the postprandial reduction in bone resorption, and our findings are compatible with such a function for GLP-2.

Early Prediction of Deep Sternal Wound Infection after Heart Operations by Alpha-1 Acid Glycoprotein and C-reactive Protein Measurements

Serum C-reactive protein (CRP) and alpha 1-acid glycoprotein (AAG) levels were studied in 188 patients undergoing heart operations with cardiopulmonary bypass. Mediastinitis or osteomyelitis of the sternum or both developed in 10 patients on postoperative day 4 to 13 (median, day 9). The mean CRP levels on day 2 were lower in patients with later deep sternal wound infection (9.1 +/- 1.5 mg/dl [mean +/- standard error]) compared with patients without major infections (14.0 +/- 0.8 mg/dl; p = 0.103 [univariate logistic regression]). AAG levels on day 2 reacted in a similar manner, yielding 78.2 +/- 5.5 mg/dl and 100.9 +/- 2.7 mg/dl, respectively (p = 0.0004). No correlation was found between CRP or AAG and duration of cardiopulmonary bypass, number of blood transfusions, or total protein levels on day 2. The white blood cell count (WBC) on day 2 was 13.1 +/- 1.7 X 10(3)/microliter for patients with infection and 9.7 +/- 0.3 for those without infection. Multivariate logistic regression analysis revealed that AAG, WBC, and CRP on day 2 were significant risk factors sufficiently predicting the probability of a deep sternal infection. After adjustment for these three variables, other variables (age, sex, total protein on day 2, diabetes mellitus, type of operation, duration of cardiopulmonary bypass, length of operation, repeat thoracotomy for bleeding, number of blood transfusions on the day of operation, intraaortic balloon pumping, reoperation, emergency operation, and surgeons professional status) were not of additional significance. The goodness of fit of the statistical model was confirmed by a high correspondence between predicted and observed cases of deep sternal infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Gastric emptying of glucose solution and associated plasma concentrations of GLP-1, GIP, and PYY before and after fundoplication

BackgroundThis study was designed to assess the relationship between gastric emptying of glucose solution and the ensuing plasma concentrations of glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and glucose-dependent insulinotropic polypeptide (GIP) in patients having undergone fundoplication for gastroesophageal reflux (GERD).Subjects and methodsIn 10 male patients the emptying of 50% glucose solution was determined scintigraphically and its relationship with plasma glucose, GLP-1, PYY, and GIP concentrations was studied before and 3 months after fundoplication.ResultsIn the first 30 min after glucose ingestion, emptying was significantly (p = 0.048) faster after fundoplication than before. Emptying and GLP-1 and GIP correlated: the faster the emptying during the first 30 min the greater the concentrations integrated over that period (p = 0.04; p = 0.01; p = 0.02). Emptying and PYY concentrations were unrelated. In the 120–180 min. period, blood glucose concentrations were lower the faster the emptying in the initial 30 min (p = 0.06) and the entire 50-min recording period (p = 0.03) had been. The GLP-1 concentrations integrated over the first 30 min correlated inversely with the integrated plasma glucose during the third hour after ingestion (p = 0.004).ConclusionsAfter fundoplication, gastric emptying may, if accelerated in its initial phases, give rise to greater and earlier increases in plasma glucose, GLP-1, and GIP concentrations and thus to reactive hypoglycemia.

Bedeutung des präoperativen Gewichtsverlusts für die perioperative Stoffwechseladaptation und das Operationsrisiko bei Patienten mit Tumoren im oberen Gastrointestinaltrakt

SummaryBody composition and energy expenditure were investigated before and 10–14 days after surgery in 44 patients with upper gastrointestinal cancer (23 esophageal and 21 gastric cancer) in order to assess the impact of preoperative weight loss on metabolic adaptation to the surgical trauma and on postoperative complications. Patients were divided in three groups with I: 0–5%, II: 5–10% and III: > 10% preoperative weight loss related to the usual body weight. 50% of the patients presented with no or just minor weight loss. Even in case of weight loss > 10% no decrease below the ideal body weight was observed. Body cell mass and fat mass were significantly (p < 0.05) reduced in group III when compared with I. Since energy expenditure and substrate oxidation rates were rather normal in most patients weight loss was considered to be due to tumor related stenosis and dysphagia. More than 50% of the energy requirements were gained from fat oxidation. General criteria of malnutrition were not fulfilled. Perioperative weight loss was lowest (1.6 ± 4.9 kg) in patients of group III related to group I (2.9 ± 1.7 kg) and II (5.0 ± 6.9 kg). Similar elevation of energy expenditure and lipid oxidation with concomitant reduction in glucose oxidation was observed in all groups of patients. This led to a similar decrease of body cell mass. Independant of preoperative weight loss major complications occurred in 8 cases — pneumonia in 6 and leakage of the anastomosis in 2 patients; no patient died. From this study can be concluded that with regard to perioperative weight loss the metabolic response to surgical trauma is adequate even in patients with marked preoperative weight loss. These patients remain compensated and preoperative weight loss is without major effect on postoperative complication rate.ZusammenfassungZur Frage des Einflusses des präoperativen Gewichtsverlusts auf die metabolische Adaptation an das Operationstrauma und auf die Häufigkeit postoperativer Komplikationen wurden 44 Patienten mit Karzinomen des oberen Gastrointestinaltrakts (23 Ösophagus-und 21 Magenkarzinome) 10–14 Tage prä- und postoperativ im Ernährungsstatus, der Körperzusammensetzung und der Stoffwechsellage untersucht. Die Patienten wurden entsprechend dem präoperativen Gewichtsverlust in den letzten 6 Monaten vor der stationären Aufnahme in 3 Gruppen unterteilt: I: Abnahme um 0–5% des Ausgangsgewichts, II: 5–10% und III: > 10%. 50% der Patienten wiesen präoperativ keinen oder nur einen geringen Gewichtsverlust auf. Auch bei hohem Gewichtsverlust wurde das jeweils errechnete ideale Körpergewicht nicht unterschritten. Körperzellund Fettmasse waren in Gruppe III signifikant (p < 0,05) niedriger als in Gruppe I. Da der Ruheenergieverbrauch bei den meisten Patienten nicht erhöht war, müssen als Ursache des Gewichtsverlusts Tumorstenose und Dysphagie, jedoch nicht ein Hypermetabolismus, angesehen werden. Mehr als 50% des Energiebedarfs wurden durch Lipidoxidation gedeckt. Insgesamt erfüllten selbst die Patienten in Gruppe III nicht die Kriterien einer Mangelernährung. Der perioperative Gewichtsverlust war in der Gruppe III am niedrigsten (1,6 ± 4,9 kg) im Vergleich zu den Gruppen I und II mit 2,9 ± 1,7 bzw. 5,0 ± 6,9 kg. In allen Gruppen wurde eine Erhöhung des Energieverbrauchs und der Fettoxidationsrate, einhergehend mit einer Hemmung der Glukoseoxidation, beobachtet. Dies resultierte in einer Verminderung der Körperzellmasse. Unabhängig vom präoperativen Gewichtsverlust kam es bei 8 Patienten zu schwerwiegenden Komplikationen mit Pneumonie in 6 und Anastomoseninsuffizienz in 2 Fällen. Kein Patient verstarb. Die metabolische Reaktion auf das Operationstrauma ist auch bei Patienten mit ausgeprägtem präoperativem Gewichtsverlust adäquat. Diese Patienten bleiben kompensiert und der präoperative Gewichtsverlust ist ohne signifikanten Einfluß auf die postoperative Komplikationsrate.

Small bowel function after surgery for chronic radiation enteritis

The retention of the gamma-emitting 75Se-homotaurocholic acid (SeHCAT) after 72 and 168 h was assessed in 10 patients after ileal resection for radiation injury (group I). 6 patients suffering from chronic postirradiation diarrhea (group II) and 6 patients in whom the ileum had been resected for other indications (group III) were also examined. The retention of SeHCAT was abnormally low (less than 50%) in all cases after 72 h and below 20% in 19 out of 21 cases after 168 h. The length of resected small bowel (groups I and III) was inversely related with SeHCAT retention after 72 h (r = 0.63; p = 0.015), but not after 168 h. There was no correlation between the diarrhea score and the extent of bowel resection, SeHCAT retention or xylose absorption. Hydrogen breath test with lactulose revealed a significantly shortened orocecal transit time in group I, compared to groups II and III. Xylose absorption was significantly reduced in patients with positive 5 g xylose-H2 breath test. In groups I and III, however, xylose absorption tended to improve with increasing time interval following resection (r = 0.79; p = 0.003). It is concluded that radiation injury in addition to small-bowel resection contributes significantly to malabsorption and diarrhea in patients after ileal resection for radiation sequelae. The chronic radiation damage seems to act mainly through impaired motility.