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Biomedical subjects

Dirk J Gouma

Publications and source records attributed to Dirk J Gouma.

At least 19 recordsLinked to original sources
PubMed2005

Locally advanced pancreatic cancer treated with radiation and 5-fluorouracil: a first step to neoadjuvant treatment?

AIM OF THE STUDY: In two institutions, a retrospective analysis was performed on patients with histologically proven locally advanced pancreatic cancer without distant metastases. The aim of this analysis is to assess whether chemoradiotherapy provides survival benefit for patients with locally advanced pancreatic cancer. METHODS: Forty-five patients from the Erasmus Medical Centre (Erasmus MC), Rotterdam, received 5-fluorouracil (5-FU) and radiotherapy and, 38 patients from the Academic Medical Centre Amsterdam (AMC) were offered the best supportive care. Radiotherapy consisted of 50 Gy external upper abdomen radiation in two courses, concomitant with intravenous 5-FU 25 mg/kg/ 24 h continuously on the first 4 days of each treatment course. RESULTS: The treatment protocol was completed in 38 of 45 patients (84%) without complications. Radiological response was evaluated in 38 patients. Ten patients (26%) showed a partial response, stable disease was seen in 6 (16%) patients and progressive disease in 22 (58%) patients. A second-look operation was performed in 8 of 10 patients (72%) showing a radiological response, in 3 patients the tumour could be resected. Median overall survival time for the Erasmus MC group (n = 45) was 9.8 months compared to 7.6 months when the best supportive care was given (AMC group, p = 0.04). CONCLUSION: Although overall survival remains poor, treatment with 5-FU and radiotherapy might benefit some patients with locally advanced pancreatic cancer.

Adenocarcinoma↗
PubMed2005

Value of CT criteria in predicting survival in patients with potentially resectable pancreatic head carcinoma.

BACKGROUND AND OBJECTIVE: Survival is often poor after resection of pancreatic tumors. We correlated the pre-operative CTs with survival to find criteria that have prognostic value. To establish the prognostic value of CT in patients with potentially resectable pancreatic head carcinoma. METHODS: In 71 consecutive patients with potentially resectable pancreatic head carcinoma, prognostic factors on CT were scored, for example, tumor size, peripancreatic infiltration, grades of vascular encasement, and local irresectability. All patients underwent surgical exploration. CT findings were compared with results of surgery and histopathology. Prognostic factors for resected and unresected tumors were analyzed using single and multivariate analysis. RESULTS: Forty-one of 71 tumors were resected (24 radical). The sensitivity, specificity, and positive predictive value of CT for surgical irresectability were 0.67, 0.63, and 0.57, respectively. For a non-radical resection, these were 0.62, 0.75, and 0.83, respectively. The median survival was 21 months for resectable tumors and 9.7 months for unresectable tumors. For resected tumors, a tumor diameter of > 3 cm (relative hazard 3.8) and CT signs of local unresectability showed a poor survival. The median survival of resected tumors <2 cm was nearly 30 months. CONCLUSION: CT signs of local irresectability and a tumor diameter of >3 cm predict a poor survival after resection.

Adult↗
PubMed2005

Incidence and management of biliary leakage after hepaticojejunostomy.

This study analyzes the change in the management of biliary leakage after hepaticojejunostomy. Between 1993 and 2003 all patients (n = 1033) were studied with a hepaticojejunostomy as part of a pancreatoduodenectomy (n = 486), proximal bile duct resection (without liver resection) (n = 35), and biliodigestive bypass for malignant (n = 302) and benign (n = 210) disease. Biliary leakage was defined as the presence of bile-stained fluid (>50 mL) in the abdominal drain more than 24 hours after surgery, proven radiologically or at relaparotomy. The studied patients were divided into two equal periods to analyze the change in management. Overall, 24 of 1033 patients (2.3%) had biliary leakage. In multivariate analysis, a body mass index greater than 35 kg/m2 (P = .012), endoscopic biliary drainage (P = .044), and an anastomosis on the segmental bile ducts (P < .001) were independent predictors of leakage. Management in the first half of the study period (1993-1998) versus the second half (1999-2003) was maintenance of operatively placed drains (18% vs. 15%, respectively, P = 1.000), percutaneous transhepatic biliary drainage (18% vs. 69%, respectively, P = .012), surgical drainage (55% vs. 8%, respectively, P = .023), and re-hepaticojejunostomy (9% vs. 8%, respectively, P = 1.000). There was no mortality in the patients with biliary leakage. Leakage after a hepaticojejunostomy is a relatively rare complication without mortality and can safely be managed with percutaneous transhepatic biliary drainage.

Biliary Tract Diseases↗
PubMed2005

Delayed massive hemorrhage after pancreatic and biliary surgery: embolization or surgery?

OBJECTIVE: To analyze the management of delayed massive hemorrhage (DMH) after major pancreatic and biliary surgery. SUMMARY BACKGROUND DATA: Despite a decreased mortality rate for pancreatic and biliary surgery, DMH is still an important cause of postoperative mortality. The aim of the present study was to analyze the management of DMH after pancreatic and biliary surgery, and specifically to assess the role of embolization and surgical intervention. METHODS: The study group (SG) consisted of 1010 patients from 1994 to 2002 who underwent pancreatic or biliary surgery (cholecystectomy excluded). Patients from a previous study (1983-1993, n = 686) were used as a historical control group (HCG). RESULTS: The incidence of DMH (SG 2.3% vs. HCG 3.2%) declined somewhat but did not differ significantly between both periods. The number of patients with a septic complication (SG 74% vs. HCG 50%) and a sentinel bleed (SG 78% vs. HCG 100%) before the onset of DMH did not differ significantly. Embolization (SG 2 of 2 patients vs. HCG 0 of 2 patients) was not used frequently. Successful outcome after surgical intervention (SG 14 of 16 patients vs. HCG 8 of 14 patients) and the surgical procedures performed to obtain hemostasis were comparable and overall mortality (SG 22% vs. HCG 29%) was comparable. CONCLUSIONS: The incidence of DMH declined somewhat from 3.2% to 2.3% over the past years. Most patients present with septic complications and a sentinel bleed before onset of DMH. Despite general acceptance of embolization in our unit, it was used infrequently in patients with DMH. Aggressive surgical intervention was the treatment of choice in patients with DMH after pancreatic or biliary surgery.

Adult↗
PubMed2005

Hospital volume and mortality after pancreatic resection: a systematic review and an evaluation of intervention in the Netherlands.

OBJECTIVES: To evaluate the best available evidence on volume-outcome effect of pancreatic surgery by a systematic review of the existing data and to determine the impact of the ongoing plea for centralization in The Netherlands. SUMMARY BACKGROUND DATA: Centralization of pancreatic resection (PR) is still under debate. The reported impact of hospital volume on the mortality rate after PR varies. Since 1994, there has been a continuous plea for centralization of PR in The Netherlands, based on repetitive analysis of the volume-outcome effect. METHODS: A systematic search for studies comparing hospital mortality rates after PR between high- and low-volume hospitals was used. Studies were reviewed independently for design features, inclusion and exclusion criteria, cutoff values for high and low volume, and outcome. Primary outcome measure was hospital or 30-day mortality. Data were obtained from the Dutch nationwide registry on the outcome of PR from 1994 to 2004. Hospitals were divided into 4 volume categories based on the number of PRs performed per year. Interventions and their effect on mortality rates and centralization were analyzed. RESULTS: Twelve observational studies with a total of 19,688 patients were included. The studies were too heterogeneous to allow a meta-analysis; therefore, a qualitative analysis was performed. The relative risk of dying in a high-volume hospital compared with a low-volume hospital was between 0.07 and 0.76, and was inversely proportional to the volume cutoff values arbitrarily defined. In 5 evaluations within a decade, hospital mortality rates were between 13.8% and 16.5% in hospitals with less than 5 PRs per year, whereas hospital mortality rates were between 0% and 3.5% in hospitals with more than 24 PRs per year. Despite the repetitive plea for centralization, no effect was seen. During 2001, 2002, and 2003, 454 of 792 (57.3%) patients underwent surgery in hospitals with a volume of less than 10 PRs per year, compared with 280 of 428 (65.4%) patients between 1994 and 1996. CONCLUSIONS: The data on hospital volume and mortality after PR are too heterogeneous to perform a meta-analysis, but a systematic review shows convincing evidence of an inverse relation between hospital volume and mortality and enforces the plea for centralization. The 10-year lasting plea for centralization among the surgical community did not result in a reduction of the mortality rate after PR or change in the referral pattern in The Netherlands.

Chi-Square Distribution↗
PubMed2004

Recurrent disease after microscopically radical (R0) resection of periampullary adenocarcinoma in patients without adjuvant therapy.

The survival rate after microscopically radical resection of pancreatic duct adenocarcinoma is still poor. Patients with ampulla of Vater and distal common bile duct adenocarcinoma indicate a much more favorable prognosis. Controversy exists as to whether adjuvant therapy could improve the outcome in these patients after resection. The aim of the present study was to analyze the pattern of recurrence in patients with periampullary adenocarcinoma after pancreatoduodenectomy. Between January 1992 and December 2002, all patients with an R0 resection were identified and used for this analysis. A total of 190 patients underwent a microscopically radical resection and received no adjuvant therapy. Of those, 72 patients were diagnosed with pancreatic duct adenocarcinoma, 86 patients were diagnosed with ampulla of Vater adenocarcinoma, and 31 patients were diagnosed with distal common bile duct adenocarcinoma. Recurrent disease was indicated in 81% of the patients with pancreatic duct adenocarcinoma, 50% of the patients with ampulla of Vater adenocarcinoma, and in 74% of the patients with bile duct adenocarcinoma. Multivariate analysis revealed that lymph node metastases were prognostic for recurrent disease in patients with pancreatic duct adenocarcinoma (P = 0.038). The depth of invasion (T4, P < 0.032) and lymph node metastases (P < 0.001) were prognostic in patients with ampulla of Vater adenocarcinoma. Poor tumor differentiation (P < 0.001) was prognostic in patients with distal bile duct adenocarcinoma. Selected patients with periampullary malignancies exhibited a high recurrence rate and should be encouraged to enroll in clinical trials for adjuvant treatment including local therapy (radiotherapy) according to the identified prognostic factors.

Ampulla of Vater↗
PubMed2004

Hand-assisted laparoscopic versus open restorative proctocolectomy with ileal pouch anal anastomosis: a randomized trial.

OBJECTIVE: The aim of the study was to evaluate postoperative recovery after hand-assisted laparoscopic or open restorative proctocolectomy with ileal pouch anal anastomosis for ulcerative colitis and familial adenomatous polyposis in a randomized controlled trial. METHODS: Sixty patients were randomized for hand-assisted laparoscopic (n = 30) or open surgery (n = 30). Primary outcome parameter was postoperative recovery in the 3 months after surgery, measured by quality of life questionnaires (SF-36 and GIQLI). Secondary parameters were postoperative morphine requirement and surgical parameters, viz. operating time, morbidity, hospital stay, and costs. RESULTS: There was no difference between the 2 procedures in quality of life assessment in the 3 months after surgery. There was a significant decline in quality of life on all scales of the SF-36 (P < 0.001) and total GIQLI score (P < 0.001) in the first 2 weeks in both groups (no significant difference between the groups). Quality of life returned to baseline levels after 4 weeks. Operating times were longer in the laparoscopic group compared with the open group (210 and 133 minutes, respectively; P < 0.001). No significant differences were found in morphine requirement. Neither morbidity nor postoperative hospital stay differed between the laparoscopic and open group (20% versus 17%, in 10 versus 11 days, respectively). Median overall costs were 16.728 for the hand-assisted laparoscopic procedure and 13.406 for the open procedure (P = 0.095). CONCLUSIONS: Recovery measured using quality of life questionnaires is comparable for hand-assisted laparoscopic or open restorative proctocolectomy with ileal pouch anal anastomosis. The laparoscopic approach is as safe, but more costly than the open procedure.

Adult↗
PubMed2004

The role of antibiotic prophylaxis in prevention of wound infection after Lichtenstein open mesh repair of primary inguinal hernia: a multicenter double-blind randomized controlled trial.

OBJECTIVE: To determine whether the use of prophylactic antibiotics is effective in the prevention of postoperative wound infection after Lichtenstein open mesh inguinal hernia repair. SUMMARY BACKGROUND DATA: A recent Cochrane meta-analysis (2003) concluded that "antibiotic prophylaxis for elective inguinal hernia repair cannot be firmly recommended or discarded." METHODS: Patients with a primary inguinal hernia scheduled for Lichtenstein repair were randomized to a preoperative single dose of 1.5 g intravenous cephalosporin or a placebo. Patients with recurrent hernias, immunosuppressive diseases, or allergies for the given antibiotic were excluded. Infection was defined using the Centers for Disease Control and Prevention criteria. RESULTS: We included 1040 patients in the study between November 1998 and May 2003. According to the intention-to-treat principle, 1008 patients were analyzed. There were 8 infections (1.6%) in the antibiotic prophylaxis group and 9 (1.8%) in the placebo group (P = 0.82). There was 1 deep infection in the antibiotic prophylaxis group and 2 in the placebo group (P = 0.57). Statistical analysis showed an absolute risk reduction of 0.19% (95% confidence interval, -1.78%-1.40%) and a number needed to treat of 520 for the total number of infections. For deep infection, the absolute risk reduction is 0.20% (95% confidence interval, -0.87%-0.48%) with a number needed to treat of 508. CONCLUSIONS: A low percentage (1.7%) of wound infection after Lichtenstein open mesh inguinal (primary) hernia repair was found, and there was no difference between the antibiotic prophylaxis or placebo group. The results show that, in Lichtenstein inguinal primary hernia repair, antibiotic prophylaxis is not indicated in low-risk patients.

Anti-Bacterial Agents↗
PubMed2004

Preoperative assessment of liver function: a comparison of 99mTc-Mebrofenin scintigraphy with indocyanine green clearance test.

BACKGROUND/AIMS: The indocyanine green (ICG) clearance test is the most frequently used test for preoperative assessment of liver parenchymal function but has its limitations. The aim of this study was to investigate the correlation between ICG clearance test and the liver uptake of 99-Technetium-labelled (99mTc)-Mebrofenin (99mTc-Mebrofenin) as measured with hepatobiliary scintigraphy. METHODS: Fifty-four patients were diagnosed as hepatocellular carcinoma (n=9), hilar tumours (n=20) and 25 patients with non-parenchymal tumours including colorectal metastasis (n=15) and miscellaneous tumours (n=10). One day prior to operation, hepatobiliary 99mTc-Mebrofenin scintigraphy was performed after intravenous injection of 85 MBq and the 15-min clearance rate of ICG (ICG-C15) was measured. RESULTS: The mean ICG-C15 was 86.86+/-1.19% (SEM). The mean 99mTc-Mebrofenin uptake rate was 12.87+/-0.52%/min. A significant correlation was obtained between 99mTc-Mebrofenin uptake rate by scintigraphy and ICG-C15 (r=0.73, P<0.0001). The mean clearance capacity of the right liver segments (79.83+/-1.63, range 47.75-95.97%) was larger than that of the left segments (20.24+/-1.55, range 6.51-52.51%). CONCLUSION: 99mTc-Mebrofenin uptake rate as assessed by scintigraphy is an efficient method for determining liver function and correlates well with ICG clearance. At the same time, 99mTc-Mebrofenin scintigraphy provides information of segmental functional liver tissue, which is of additional use when planning liver resection.

Adult↗
PubMed2003

Cholestatic interleukin-6-deficient mice succumb to endotoxin-induced liver injury and pulmonary inflammation.

Circulating and hepatic interleukin (IL)-6 levels are strongly increased during clinical and experimental cholestasis. Cholestatic liver injury is associated with increased susceptibility to endotoxin-induced toxicity. To determine the role of IL-6 herein, extrahepatic cholestasis was induced by bile duct ligation (BDL) in IL-6-gene deficient (IL-6(-/-)) and normal (IL-6(+/+)) mice. BDL elicited increased levels of hepatic IL-6 mRNA and protein in normal mice. Hepatocellular injury 2 weeks after BDL was similar in IL-6(-/-) and IL-6(+/+) mice as demonstrated by clinical chemistry and histopathology. Administration of endotoxin to cholestatic mice 2 weeks after BDL was associated with enhanced cytokine release, severe liver damage, and death when compared with sham-operated mice. Effects of endotoxin were largely similar in sham-operated IL-6(-/-) and IL-6(+/+) mice, but cholestatic IL-6(-/-) mice were more susceptible to the toxic effects of endotoxin, as reflected by increased cytokine release, more profound liver injury and lung inflammation, and higher mortality. Although endogenous IL-6 is not important in the development of liver injury after experimentally induced obstructive jaundice, this cytokine plays an important role in decreasing hypersensitivity to endotoxin in cholestatic mice.

Animals↗
PubMed2003

Interferon-gamma increases monocyte HLA-DR expression without effects on glucose and fat metabolism in postoperative patients.

Tissue injury is associated with decreased cellular immunity and enhanced metabolism. Immunodepression is thought to be counteracted by interferon (IFN)-gamma, which increases human leukocyte antigen (HLA)-DR expression. Hypermetabolism could be enhanced by IFN-gamma because cytokines induce a hypermetabolic response to stress. In healthy humans, IFN-gamma enhanced HLA-DR expression without effects on glucose and fat metabolism. In the present study, we evaluated whether IFN-gamma lacks potential harmful side effects on metabolic and endocrine pathways while maintaining its beneficial effects on the immune system under conditions in which the inflammatory response system is activated. In 13 patients scheduled for major surgery, we studied HLA-DR expression on peripheral blood monocytes before surgery and postoperatively randomized the patients into an intervention and a placebo group. Subsequently, we evaluated the effects of a single dose of IFN-gamma vs. saline on short-term monocyte activation, glucose and lipid metabolism, and glucose and lipid regulatory hormones. HLA-DR expression on monocytes was restored from postoperative levels of 54% (42-60%; median and interquartiles) to 92% (91-96%) 24 h after IFN-gamma administration but stayed low in the placebo-treated patients. IFN-gamma did not affect glucose metabolism (plasma glucose, rate of appearance and disappearance of glucose) and lipid metabolism (plasma glycerol, plasma free fatty acids, and rates of appearance and disappearance of glycerol). IFN-gamma had no effect on plasma cortisol, adrenocorticotropic hormone, growth hormone, insulin, C-peptide, glucagon, epinephrine, and norepinephrine concentrations. We conclude that IFN-gamma exerts a favorable effect on cell-mediated immunity in patients after major surgery without effects on glucose and lipid metabolism.

Aged↗
PubMed2003

Results of postoperative radiotherapy for resectable hilar cholangiocarcinoma.

The aim of this study was to assess the value of radiotherapy, and especially intraluminal brachytherapy, after resection of hilar cholangiocarcinoma by analyzing long-term complications and survival. Between 1983 and 1998, 112 patients underwent resection of a hilar cholangiocarcinoma. Of the 91 patients who survived the postoperative period, 20 patients had no additional radiotherapy, 30 patients had only external radiotherapy (46 +/- 11 Gy), and 41 patients had a combination of external (42 +/- 5 Gy) and intraluminal brachytherapy (10 +/- 2 Gy). Overall, 88% of the patients had late complications, with a significantly higher rate of complications occurring among patients receiving external beam irradiation and brachytherapy. Second to abdominal pain (56%), cholangitis (49%) was the most frequent complication and occurred significantly more often in patients who had received brachytherapy. Retrograde bile leakage after closure of the temporary jejunostomy was a troublesome complication in 24% of patients treated with brachytherapy. Overall median survival after treatment with adjuvant radiotherapy was longer than after resection without additional radiation (24 months versus 8 months, respectively). There was, however, no significant benefit from the use of intraluminal brachytherapy. In conclusion, additional radiotherapy after resection of hilar cholangiocarcinoma significantly improved survival and is recommended by giving external beam irradiation but not intraluminal brachytherapy.

Abdominal Pain↗
PubMed2003

Decrease in core liver temperature with 10 degrees C by in situ hypothermic perfusion under total hepatic vascular exclusion reduces liver ischemia and reperfusion injury during partial hepatectomy in pigs.

OBJECTIVE: We attempted to assess liver ischemia/reperfusion injury under a mild decrease in core liver temperature of 10 degrees C by in situ hypothermic perfusion during ischemia. METHODS: Liver ischemia was induced in pigs by total hepatic vascular exclusion with concomitant in situ perfusion with hypothermic (4 degrees C) Ringer-glucose (cold perfused group, core liver temperature maintained at 28 degrees C), with normothermic (38 degrees C) Ringer-glucose (warm perfused group) or without in situ perfusion (control group). RESULTS: In the cold perfused, warm perfused, and control groups, 24-hour survival was 5/5, 0/5, and 3/5, respectively. Hemodynamic parameters in the cold perfused group remained stable, whereas pigs in both other groups required circulatory support. Plasma AST and interleukin-6 levels were lower in the cold perfused group than in both other groups. Hepatocellular function was best preserved in the cold perfused group as indicated by complete recovery of bile production during reperfusion and no loss of indocyanine green clearance capacity. In both other groups, bile production and indocyanine green clearance capacity were reduced significantly. The hyaluronic acid uptake capacity of pigs in the cold perfused group or control group did not differ, indicating preserved sinusoidal endothelial cell function. Histopathologic injury scores during reperfusion were significantly lower in the cold perfused group when compared to both other groups. CONCLUSIONS: A mild decrease in core liver temperature of 10 degrees C by in situ hypothermic liver perfusion during ischemia protects the liver from ischemia/reperfusion injury. This protection appears to be related to cooling of the liver rather than to the washout of blood during perfusion.

Animals↗
PubMed2003

Effect of in situ hypothermic perfusion on intrahepatic pO2 and reactive oxygen species formation after partial hepatectomy under total hepatic vascular exclusion in pigs.

AIM: This study examined attenuation of ischemia and reperfusion (I/R) induced liver injury during liver resections by hypothermic perfusion of the liver under total hepatic vascular exclusion (THVE). METHOD: Reactive oxygen species (ROS) formation, microcirculatory integrity and endothelial cell damage were investigated. Left hemihepatectomy (LHX) was performed without in situ perfusion (control-LHX, n = 5) or with concomitant in situ perfusion with hypothermic (4 degrees C) Ringer-glucose (cold-LHX, n = 5) or normothermic (38 degrees C) Ringer-glucose (warm-LHX, n = 5). Glutathione (GSH) and malondialdehyde (MDA) concentrations, tissue pO2 levels and hyaluronic acid (HA) uptake capacity were determined. RESULTS: After cold, warm and control-LHX, 24 h survival was 5/5, 0/5 and 3/5, respectively. GSH levels were best preserved after cold-LHX during reperfusion. MDA levels increased in all groups without significant differences between the groups during reperfusion. Tissue pO2 levels increased after cold-LHX whereas after warm-LHX and control-LHX, pO2 levels decreased during reperfusion. HA uptake capacity remained normal after cold-LHX. After warm-LHX and control-LHX, HA uptake capacity decreased after 6 h of reperfusion but recovered after 24 h of reperfusion in the control-LHX group. CONCLUSION: Moderate hypothermic perfusion protects the liver from I/R injury during LHX under THVE. This protective effect depended on maintenance of liver microcirculation rather than a reduction in ROS formation.

Animals↗
PubMed2003

Laparoscopic staging and subsequent palliation in patients with peripancreatic carcinoma.

OBJECTIVE: To test the hypothesis that laparoscopic staging improves outcome in patients with peripancreatic carcinoma compared to standard radiology staging. SUMMARY BACKGROUND DATA: Diagnostic laparoscopy of peripancreatic malignancies has been reported to improve assessment of tumor stage and to prevent unnecessary exploratory laparotomies in 10% to 76% of patients. METHODS: Laparoscopy and laparoscopic ultrasound were performed in 297 consecutive patients with peripancreatic carcinoma scheduled for surgery after radiologic staging. Patients with pathology-proven unresectable tumors were randomly allocated to either surgical or endoscopic palliation. All others underwent laparotomy. RESULTS: Laparoscopic staging detected biopsy-proven unresectable disease in 39 patients (13%). At laparotomy, unresectable disease was found in another 72 patients, leading to a detection rate for laparoscopic staging of 35%. In total, 145 of the 197 patients classified as having "possibly resectable" disease after laparoscopic staging underwent resection (74%). Average survival in the group of 14 patients with biopsy-proven unresectable tumors randomly allocated to endoscopic palliation was 116 days, with a mean hospital-free survival of 94 days. The corresponding figures were 192 days and 164 days in the 13 patients allocated to surgical palliation. CONCLUSIONS: Because of the limited detection rate for unresectable metastatic disease and the likely absence of a large gain after switching from surgical to endoscopic palliation, laparoscopic staging should not be performed routinely in patients with peripancreatic carcinoma.

Aged↗
PubMed2003

The need for a prophylactic gastrojejunostomy for unresectable periampullary cancer: a prospective randomized multicenter trial with special focus on assessment of quality of life.

OBJECTIVE: To evaluate the effect of a prophylactic gastrojejunostomy on the development of gastric outlet obstruction and quality of life in patients with unresectable periampullary cancer found during explorative laparotomy. SUMMARY BACKGROUND DATA: Several studies, including one randomized trial, propagate to perform a prophylactic gastrojejunostomy routinely in patients with periampullary cancer found to be unresectable during laparotomy. Others suggest an increase of postoperative complications. Controversy still exists in general surgical practice if a double bypass should be performed routinely in these patients. METHODS: Between December 1998 and March 2002, patients with a periampullary carcinoma who were found to be unresectable during exploration were randomized to receive a double bypass (hepaticojejunostomy and a retrocolic gastrojejunostomy) or a single bypass (hepaticojejunostomy). Randomization was stratified for center and presence of metastases. Patients with gastrointestinal obstruction and patients treated endoscopically for more than 3 months were excluded. Primary endpoints were development of clinical gastric outlet obstruction and surgical intervention for gastric outlet obstruction. Secondary endpoints were mortality, morbidity, hospital stay, survival, and quality of life, measured prospectively by the EORTC-C30 and Pan26 questionnaires. It was decided to perform an interim analysis after inclusion of 50% of the patients (n = 70). RESULTS: Five of the 70 patients randomized were lost to follow-up. From the remaining 65 patients, 36 patients underwent a double and 29 a single bypass. There were no differences in patient demographics, preoperative symptoms, and surgical findings between the groups. Clinical symptoms of gastric outlet obstruction were found in 2 of the 36 patients (5.5%) with a double bypass, and in 12 of the 29 patients (41.4%) with a single bypass (P = 0.001). In the double bypass group, one patient (2.8%) and in the single bypass group 6 patients (20.7%) required (re-)gastrojejunostomy during follow-up (P = 0.04). The absolute risk reduction for reoperation in the double bypass group was 18%, and the numbers needed to treat was 6. Postoperative morbidity rates, including delayed gastric emptying, were 31% in the double versus 28% in the single bypass group (P = 0.12). Median postoperative length of stay was 11 days (range 4-76 days) in the double versus 9 days (range 6-20 days) in the single bypass group (P = 0.06); median survival was 7.2 months in the double versus 8.4 months in the single bypass group (P = 0.15). No differences were found in the quality of life between both groups. After surgery most quality of life scores deteriorated temporarily and were restored to their baseline score (t = -1) within 4 months. CONCLUSIONS: Prophylactic gastrojejunostomy significantly decreases the incidence of gastric outlet obstruction without increasing complication rates. There were no differences in quality of life between the two groups. Together with the previous randomized trial from the Hopkins group, this study provides sufficient evidence to state that a double bypass consisting of a hepaticojejunostomy and a prophylactic gastrojejunostomy is preferable to a single bypass consisting of only a hepaticojejunostomy in patients undergoing surgical palliation for unresectable periampullary carcinoma. Therefore, the trial was stopped earlier than planned.

Aged↗
PubMed2003

Interleukin-18 facilitates the early antimicrobial host response to Escherichia coli peritonitis.

To determine the role of endogenous interleukin-18 (IL-18) during peritonitis, IL-18 gene-deficient (IL-18 KO) mice and wild-type mice were intraperitoneally (i.p.) infected with Escherichia coli, the most common causative agent found in septic peritonitis. Peritonitis was associated with a bacterial dose-dependent increase in IL-18 concentrations in peritoneal fluid and plasma. After infection, IL-18 KO mice had significantly more bacteria in the peritoneal lavage fluid and were more susceptible for progression to systemic infection at 6 and 20 h postinoculation than wild-type mice. The relative inability of IL-18 KO mice to clear E. coli from the abdominal cavity was not due to an intrinsic defect in the phagocytosing capacity of their peritoneal macrophages or neutrophils. IL-18 KO mice displayed an increased neutrophil influx into the peritoneal cavity, but these migratory neutrophils were less activate, as reflected by a reduced CD11b surface expression. These data suggest that endogenous IL-18 plays an important role in the early antibacterial host response during E. coli-induced peritonitis.

Animals↗