Arnulf Thiede

Procalcitonin in Early Detection of Postoperative Complications

Background: A prospective clinical study was performed to assess the accuracy of procalcitonin in 70 patients with elective colorectal or aortal surgery and to compare it with inflammatory mediators. Also the early prediction of complications and the outcome of these patients was taken into account. Methods: Laboratory variables and cytokine determination were obtained preoperatively, on the day of operation and postoperatively on a daily basis from day 1 to 5, and on days 7 and 10 in the colorectal group and in the aortal surgery group at different times on the operation day after aortal clamping. The main outcome criteria were early recognition of complications and alterations in the production of procalcitonin and cytokines in order to detect severe infective complications. Results: Procalcitonin was closely related to postoperative complications with significantly elevated levels at day 1 after surgery. The plasma concentrations of IL-6 increase on days 1–3 without a difference in the groups, also C-reactive protein demonstrates no differences. Conclusion: Procalcitonin presents itself as a new parameter of infection and sepsis. In the postoperative period PCT seems to be an interesting marker of early prediction of infective complications when high postoperative levels are found. Under routine conditions procalcitonin is a valid reproducible and detectable parameter.

Growth of human gastric cancer cells in nude mice is delayed by a ketogenic diet supplemented with omega-3 fatty acids and medium-chain triglycerides

BackgroundAmong the most prominent metabolic alterations in cancer cells are the increase in glucose consumption and the conversion of glucose to lactic acid via the reduction of pyruvate even in the presence of oxygen. This phenomenon, known as aerobic glycolysis or the Warburg effect, may provide a rationale for therapeutic strategies that inhibit tumour growth by administration of a ketogenic diet with average protein but low in carbohydrates and high in fat enriched with omega-3 fatty acids and medium-chain triglycerides (MCT).MethodsTwenty-four female NMRI nude mice were injected subcutaneously with tumour cells of the gastric adenocarcinoma cell line 23132/87. The animals were then randomly split into two feeding groups and fed either a ketogenic diet (KD group; n = 12) or a standard diet (SD group; n = 12) ad libitum. Experiments were ended upon attainment of the target tumor volume of 600 mm3 to 700 mm3. The two diets were compared based on tumour growth and survival time (interval between tumour cell injection and attainment of target tumour volume).ResultsThe ketogenic diet was well accepted by the KD mice. The tumour growth in the KD group was significantly delayed compared to that in the SD group. Tumours in the KD group reached the target tumour volume at 34.2 ± 8.5 days versus only 23.3 ± 3.9 days in the SD group. After day 20, tumours in the KD group grew faster although the differences in mean tumour growth continued significantly. Importantly, they revealed significantly larger necrotic areas than tumours of the SD group and the areas with vital tumour cells appear to have had fewer vessels than tumours of the SD group. Viable tumour cells in the border zone surrounding the necrotic areas of tumours of both groups exhibited a glycolytic phenotype with expression of glucose transporter-1 and transketolase-like 1 enzyme.ConclusionApplication of an unrestricted ketogenic diet enriched with omega-3 fatty acids and MCT delayed tumour growth in a mouse xenograft model. Further studies are needed to address the impact of this diet on other tumour-relevant functions such as invasive growth and metastasis.

Morbidity of Temporary Loop Ileostomy in Patients With Colorectal Cancer

PurposeThis study was designed to quantify the temporary loop ileostomy-related morbidity in patients with colorectal cancer and contrast the morbidity rates after ileostomy closure before, during, and after the start of adjuvant therapy.MethodsBetween 1997 and 2004, 120 patients with colorectal carcinoma underwent colorectal resection and creation of a temporary loop ileostomy to protect the low anastomosis. Stoma-related complications and perioperative morbidity after ileostomy closure were assessed retrospectively by reviewing the medical records.ResultsSixteen of the 120 patients (13.3 percent) suffered stoma-related complications, requiring early ileostomy closure in three. After ileostomy closure, anastomotic leakage of the ileoileostomy occurred in 3 of the 120 patients (2.5 percent), 2 of them died postoperatively (1.7 percent). The rate of minor complications (16.7 percent in all patients) was much higher in patients undergoing adjuvant chemotherapy or radiochemotherapy (25.5 percent) than in patients receiving no additional therapy (9.2 percent). In the former patients, there was a trend toward fewer complications when ileostomy closure was performed before (12.5 percent), rather than during (42.9 percent) or after (21.2 percent), the start of adjuvant therapy.ConclusionsThe morbidity following closure of a temporary loop ileostomy in colorectal cancer patients is much higher in patients receiving adjuvant chemotherapy or radiochemotherapy. The morbidity, however, might possibly be lowered to the level of patients receiving no additional therapy if ileostomy closure is performed before the start of adjuvant therapy.

Long-term benefits of Roux-en-Y pouch reconstruction after total gastrectomy: a randomized trial.

Objective:Roux-en-Y reconstruction with and without jejunal pouch was compared in a randomized controlled trial to identify the optimal reconstruction procedure in terms of quality of life. Background Data:Randomized trials comparing techniques of reconstruction after total gastrectomy have shown controversial results. Methods:One hundred and thirty-eight patients with gastric cancer were intraoperatively randomized for Roux-en-Y reconstruction with pouch (n = 71) or without pouch (n = 67) after gastrectomy and stratified into curative or palliative resection. Intra- and postoperative complications were recorded. Body weight and quality of life were determined every 6 months with a follow-up of up to 12 years. Results:Both groups were comparable for age, sex, incidence of concomitant disease, and staging. There were no differences in operative time, postoperative complications, and mortality. Short- and long-term weight loss was similar in both groups. In the first postoperative year, there were no benefits of pouch reconstruction in terms of quality of life, independent of the resection status. In the third, fourth, and fifth year after surgery quality of life was significantly improved for patients with a pouch. Conclusions:Roux-en-Y pouch reconstruction after gastrectomy is simple to perform and safe. Long-term survivors benefit from pouch reconstruction. Therefore, a pouch is recommended for patients with a good prognosis.

CURATIVE-INTENT RADIATION THERAPY IN ANAL CARCINOMA : QUALITY OF LIFE AND SPHINCTER FUNCTION

In 22 colostomy-free survivors of curative-intent radiation therapy or chemoradiation for anal carcinoma, measurement of the Gastrointestinal Quality of Life Index (GIQLI) revealed a mean 114 of a maximum 144 points, as compared to 121 in healthy volunteers (n = 150) and 113 in patients with benign anorectal diseases (n = 325). Sixteen patients underwent anorectal manometry to determine anal sphincter length (SL), resting pressure (RP), maximum squeeze pressure (MSP), rectal compliance (RC) and relaxation of the internal anal sphincter (RIAS). SL, RP and MSP were significantly lower in anal carcinoma patients than in healthy volunteers. Complete continence was detected in 56% of patients.

Influence of tumor position on accuracy of endorectal ultrasound staging.

Endorectal ultrasound is a well-established method of preoperative staging of rectal neoplastic lesions. PURPOSE: This study was undertaken to evaluate whether tumor site (in terms of height) and position (with respect to the rectal circumference) have an influence on the reliability of endoluminal ultrasound staging. METHODS: From January 1991 to May 1996, 154 consecutive patients with a total of 162 rectal tumors were examined preoperatively using endorectal ultrasound. Apart from staging all tumors using the uT/uN classification, tumor level and tumor position were recorded prospectively. Neoplasms were subdivided into low rectal (0–6 cm from the anal verge), mid rectal (7–12 cm), and higher lesions (>12 cm). Furthermore, the lumen was divided into an anterior, left lateral, posterior, and right lateral position, and all tumors, apart from circular lesions (n=9), were subclassified accordingly. RESULTS: Overall, we found 40 (25 percent) adenomas, 15 (9 percent) T1, 29 (18 percent) T2, 67 (41 percent) T3, and 11 (7 percent) T4 lesions. Overall accuracy was 78 percent. Staging accuracy for low rectal tumors (n=41) was 68 percent, whereas 76 and 88 percent of mid (n=96) and high (n=25) neoplasms were staged correctly, respectively. The difference was not statistically significant. With regard to position, 47 tumors were situated anteriorly (77 percent accuracy), 42 in the left lateral position (69 percent accuracy), 33 posteriorly (73 percent accuracy), and 31 in the right lateral position (81 percent accuracy). Differences did not reach statistical significance. CONCLUSION: Endorectal ultrasound is currently the best method for preoperative assessment of the depth of infiltration of rectal tumors. However, rectal anatomy seems to affect staging accuracy in the lower rectum because the structure of the ampulla recti renders endosonographic examination more difficult. In addition, endosonographic layers are less well defined at this level. Both factors contribute to a lower reliability and predictive value of endorectal ultrasound staging in the lower rectum, although statistical significance was not reached in this study. On the other hand, tumor position with respect to rectal circumference does not influence the predictive value of endorectal ultrasound.

Combination of endoscopic argon plasma coagulation and antireflux surgery for treatment of Barrett's esophagus.

Columnar-lined epithelium with specialized intestinal metaplasia of the esophagus (i.e., Barrett’s esophagus) is a premalignant condition caused by chronic gastroesophageal reflux disease. Progression of intestinal metaplasia may be avoided by antirefiux surgery, whereas regeneration of esophageal mucosa could be achieved by endoscopic argon plasma coagulation (EAPC). The aim of this prospective study was to show the early results of a combination of EAPC and antireflux surgery. Thirty patients with Barrett’s esophagus were treated between August 1996 and December 1999. Regeneration of esophageal mucosa was achieved with several sessions of EAPC under general anesthesia. All patients were receiving a double dose of proton pump inhibitors. Endoscopic follow-up was performed 6 to 8 weeks after the last session. Antireflux surgery (Nissen [n = 26] or Toupet In = 4] fundoplication) followed complete regeneration of the squamous epithelium in the esophagus. One year after laparoscopic fundopfication and EAPC follow-up with endoscopy and quadrant biopsies of the esophagus, 24-h0ur pH monitoring and esophageal manonletry were performed. All 30 patients showed complete regeneration of the squamous epithelium after a median of two sessions (range 1 to 7) of EAPC. Twenty-two patients underwent 1-year follow-up studies. All showed endoscopically an intact fundic wrap. Recurrence of a 1 cm segment of Barrett’s epithelium without dysplasia was present in two patients, both of whom had recurrent acid reflux due to failure of their antireflux procedure. Our results indicate that the combination of EAPC and antireflux surgery is an effective treatment option in patients with Barrett’s esophagus with gastroesophageal reflux disease. Long-term follow-up of this therapy is necessary to evaluate its effect on cancer risk in Barrett’s esophagus.

Overview on compression anastomoses: biofragmentable anastomosis ring multicenter prospective trial of 1666 anastomoses.

Abstract. This study represents a European prospective clinical multicenter trial and was undertaken to evaluate the applicability of the biofragmentable anastomosis ring (BAR) as a routine anastomotic tool in teaching hospitals. The trial results analyzed consisted of 1666 BAR anastomoses performed in 1360 patients from March 1989 to May 1996 in the upper (1042 anastomoses) and lower (624 anastomoses) gastrointestinal (GI) tract. Only patients selected for elective procedures and having previously undergone orthograde bowel cleansing were entered into the trial. In the upper GI tract six anastomoses (0.58%) developed clinically relevant and radiologically detectable leaks with indications for reoperation. In the lower GI tract 42 (6.73%) anastomoses showed a radiologically detectable leak with clinical manifestations in 28 cases (4.48%). Reoperation was performed in 18 cases (2.80%). The overall leakage rate with clinical relevance was 2.04%. Three gastrojejunostomy episodes of bleeding were observed (0.18%) at the BAR anastomotic site. During the early postoperative course there was no ileus due to obstruction of a BAR anastomosis. Reintroduction of diet after the operation was not delayed. In two centers a follow-up evaluation reported no BAR-related late anastomotic stenoses. There were no intraoperative deaths, but 54 patients died postoperatively. Peritonitis following anastomotic leakage was responsible for postoperative deaths in four cases; three of them were related to BAR anastomoses. In conclusion, the BAR anastomotic procedure is an established, rapid, simple to learn, highly standardized, safe technique with the advantage of no persistent foreign material in the anastomotic region and therefore no induction of stenosis. At present, the application of anastomoses in various segments of the GI tract, from the stomach to the middle third of the rectum, can be recommended.

The morphology of islets within the porcine donor pancreas determines the isolation result: successful isolation of pancreatic islets can now be achieved from young market pigs.

Clinical islet allotransplantation has become an increasingly efficient “routine ” therapy in recent years. Shortage of human donor organs leads to porcine pancreatic islets as a potential source for islet xenotransplantation. Yet it is still very difficult to isolate sufficient numbers of intact porcine islets, particularly from young market pigs. In the following study islets were successfully isolated from retired breeders [4806 ± 720 islet equivalents per gram organ (IEQ/g); n = 25; 2–3 years old; RB] and also from young hybrid pigs [2868 ± 260 IEQ/g; n = 65; 4–6 months old; HY] using LiberasePI and a modified version of Ricordis digestion-filtration technique. As expected, isolations from RB showed significantly better results (p < 0.002). A retrospective histological analysis of almost all donor pancreases showed that the majority of organs from RB (80%) contained mainly large islets (diameter >200 μm), in contrast to only 35% of all pancreases from HY. Remarkably, the islet size in situ, regardless whether detected in RB or HY, strongly determined the isolation result. A donor organ with predominantly large islets resulted in significantly higher numbers of IEQs compared with a donor organ with predominantly small islets [RBLarge Islets: 5680 ± 3,318 IEQ/g n = 20); RBSmall Islets: 1353 ± 427 IEQ/g (n = 5); p < 0.02]. In addition, isolation results were strongly influenced by the quality of the LiberasePI batch, and therefore single batch testing is invariably required. Purification was performed using Ficoll or OptiPrep™ density gradient centrifugation manually or in the COBE cell processor. Although islet purity was highest when OptiPrep™ was used, final islet yields did not differ between the different purification methods. Our study demonstrates that islet size in situ is an extremely critical parameter for highly successful islet isolation; consequently, we are now performing a morphological screening of each donor organ prior to the isolation process. Under these conditions highly successful isolations can reliably be performed even from young market pigs.

Inter- and intraindividual reproducibility of anorectal manometry

Background: This study investigates the inter- and intraindividual variability of normal values and, thus, the reproducibility of anorectal manometry. Materials and Methods: Following a standardized protocol, three anorectal manometries were performed 4 h apart on 2 days of investigation, with an interval of 4 weeks, in ten healthy volunteers. Measured parameters in all 60 manometries were: sphincter length (SL), resting pressure (RP), maximum squeeze pressure (MSP), relaxation of the internal anal sphincter (RIAS), and rectal compliance (RC). Interindividual variability was expressed as standard deviation from calculated mean values and intraindividual variability was tested with Wilcoxons test for tied samples and Spearmans rank correlation test. Results: A large interindividual variability was found for all measured parameters, except for SL, reflecting the extensive absolute range of measured values. Median intraindividual variability among the six individual measurements and between both measurement days revealed that MSP, RIAS and RC are parameters which were not reproducible in this volunteer study. A significant correlation between the results of the repetitive measurements and, thus, a good reproducibility was only found for the parameters SL and RP. Conclusions: Anorectal manometry has only limited diagnostic value; although rather exact quantifications of individual para-meters can be achieved, the impact of these measurements should be regarded rather critically, since only SL and RP appeared to be reproducible parameters.