Multicentre study of multidisciplinary team assessment of pancreatic cancer resectability and treatment allocation.

BACKGROUND: Multidisciplinary team (MDT) meetings have been adopted widely to ensure optimal treatment for patients with cancer. Agreements in tumour staging, resectability assessments and treatment allocation between different MDTs were assessed. METHODS: Of all patients referred to one hospital, 19 patients considered to have non-metastatic pancreatic cancer for evaluation were selected randomly for a multicentre study of MDT decisions in seven units across Northern Europe. Anonymized clinical information and radiological images were disseminated to the MDTs. All patients were reviewed by the MDTs for radiological T, N and M category, resectability assessment and treatment allocation. Each MDT was blinded to the decisions of other teams. Agreements were expressed as raw percentages and Krippendorff's α values, both with 95 per cent confidence intervals. RESULTS: A total of 132 evaluations in 19 patients were carried out by the seven MDTs (1 evaluation was excluded owing to technical problems). The level of agreement for T, N and M categories ranged from moderate to near perfect (46·8, 61·1 and 82·8 per cent respectively), but there was substantial variation in assessment of resectability; seven patients were considered to be resectable by one MDT but unresectable by another. The MDTs all agreed on either a curative or palliative strategy in less than half of the patients (9 of 19). Only fair agreement in treatment allocation was observed (Krippendorff's α 0·31, 95 per cent c.i. 0·16 to 0·45). There was a high level of agreement in treatment allocation where resectability assessments were concordant. CONCLUSION: Considerable disparities in MDT evaluations of patients with pancreatic cancer exist, including substantial variation in resectability assessments.

A bridging stent to surgery in patients with esophageal and gastroesophageal junction cancer has a dramatic negative impact on patient survival: A retrospective cohort study through data acquired from a prospectively maintained national database.

This study aimed to assess the impact of esophageal stenting on postoperative complications and survival in patients with obstructing esophageal and gastroesophageal junction (GEJ) cancer. All patients treated without neoadjuvant therapy that had an R0-resection performed for esophageal and GEJ cancer between January 2003 and December 2010 were identified from a prospectively maintained database. Data on stenting, postoperative mortality, morbidity, recurrence-free survival, complications, and length of hospital stay were collected. Kaplan-Meier plots for survival and recurrence-free survival curves were constructed for R0 resected patients. Data were compared between the stent and no-stent group by nonparametric tests. Two hundred seventy three consecutive R0 resected patients with esophageal or GEJ cancer were identified. Of these patients, 63 had a stent as a bridge to surgery. The male/female ratio was 2.64 (198/75) with a median age in the stent group (SG) of 65.1 versus 64.3 in the no stent group (NSG). Patients were comparable with respect to gender, age, smoking, TNM-classification, oncological treatment, hospital stay, tumor location, and histology. The median survival in the SG was 11.6 months compared with 21.3 months for patients treated without a bridging stent (P < 0.001). There were no statistically significant differences in 30-day mortality between the two groups, but NSG patients exhibited a significantly better two-year survival (P = 0.017). The median recurrence-free survival was 9.1 months for the SG compared with 15.2 months for the NSG. The use of a stent as a bridging procedure to surgery in patients treated without neaoadjuvant therapy for an esophageal or GEJ cancer that later underwent R0 resection decreased the two year survival and the recurrence-free survival.

Partial liver ischemia is followed by metabolic changes in the normally perfused part of the liver during reperfusion.

BACKGROUND: Temporary vascular in- and outflow occlusion is an effective technique for bleeding control during liver resection. However, occlusion can result in ischemia/reperfusion (I/R) injury to the liver. The aim of this study in a porcine model was to investigate the effect of in- and outflow occlusion of part of the liver on the metabolism of the normally perfused parenchyma of the same liver measured by microdialysis. METHODS: Eight pigs underwent laparotomy. A microdialysis catheter was inserted into in the left and right part of the liver, respectively. Microdialysis samples were collected every 30 min. Occlusion of the left part of the liver was achieved for 60 min, followed by 5 h of reperfusion. Samples were analyzed for glucose, lactate, pyruvate and glycerol. Blood samples were drawn to determine standard liver and biochemical parameters. RESULTS: Comparing the ischemic part of the liver with the normally perfused part, significant differences in the levels of lactate, pyruvate and glycerol were found. During reperfusion, similar and continuous decreases below baseline levels were observed for lactate and pyruvate in both the ischemic and normally perfused part of the liver. No significant changes in liver parameters or blood glucose levels were seen. CONCLUSIONS: Partial ischemia of the liver is without effects on metabolism in the normally perfused part. Metabolic changes in the ischemic part of the liver were reversible. However, partial liver ischemia was followed by similar continuous decreases in lactate and pyruvate levels in the whole liver, even though the ischemic insult was not detectable in transaminase levels.

Cytokine changes during warm ischemia and reperfusion of the pig liver with or without preconditioning.

BACKGROUND: Hepatic inflow occlusion results in ischemia-reperfusion injury. The aim of the present porcine study was to investigate whether the pro- and anti-inflammatory cytokine response is involved in mediating the protective effect of ischemic preconditioning (IPC) during, and after warm liver ischemia. METHODS: Fifteen randomized pigs--7 non-IPC and 8 (IPC)--underwent laparotomy followed by 60 min of total ischemia with or without IPC continued by 3 h of reperfusion. Plasma cytokines (IL-6, IL-8, IL-10, and TNF-alpha) were measured during the study period as well as liver parameters (alanine-aminotransferase, alkaline phosphatase, bilirubin, and prothrombin time). RESULTS: In the IPC group, IL-6 increased significantly during reperfusion compared to baseline and the non-IPC group. TNF-alpha increased nonsignificantly in the non-IPC group, while the levels remained stable in the IPC group. IL-8 and IL-10 increased in both groups after reperfusion. Only minor differences were observed in liver parameters. CONCLUSIONS: Warm liver ischemia with or without IPC activates inflammatory cytokines. IL-6 increased significantly in the IPC group compared to the non-IPC group, while the opposite was observed for TNF-alpha. These cytokine changes may be involved in the hepatoprotective mechanism induced by IPC.

FDG-PET improves management of patients with colorectal liver metastases allocated for local treatment: a consecutive prospective study.

BACKGROUND AND AIM: Colorectal cancer is a common cancer in the Nordic countries and 50% of the patients develop liver metastases. Liver resection may result in long term survival. Proper staging is therefore essential and CT is the standard imaging modality. We examined whether additional FDG-PET improves therapeutic management of patients with colorectal liver metastases. PATIENTS AND METHODS: Fifty-four consecutive patients were enrolled. Each patient had a treatment plan made based on our standard evaluation. The patients then had a PET scan and the treatment plan was re-evaluated, taking these results into account. RESULTS: In 76% of the cases, PET did not change the treatment plan due to complete concordance with CT. In another 19% of the cases, the plan was altered due to finding of more liver lesions by PET than by CT (four patients), fewer or no liver lesions (three patients), and extrahepatic lesions not visible on CT (three patients). In 5% of the cases, non-concordance between PET and CT did not change the therapeutic plan. CONCLUSION: Pre-treatment FDG-PET, used supplementary to CT, improved the treatment plan in one fifth of the patients with colorectal liver metastases.

Impact of Body Mass Index on Complications and Survival after Surgery for Esophageal and Gastro-Esophageal-Junction Cancer.

BACKGROUND AND AIMS: The impact of body mass index on complications and survival in patients undergoing esophagectomy has been extensively studied with conflicting results. In this study, we assess the impact of body mass index on complications and survival following surgery for esophageal and gastro-esophageal-junction cancer in a Danish population. MATERIAL AND METHODS: We identified 285 consecutive patients, who underwent curative-intended treatment for esophageal and gastro-esophageal-junction cancer in the period 2003-2010. We manually reviewed the electronic medical records of all patients included in the study. Body mass index was calculated as weight in kilograms divided by height in meters squared. We grouped patients according to their body mass index, using the World Health Organization definition, as underweight (body mass index < 18.5 kg/m2), normal weight (body mass index: 18.5-24.9 kg/m2), overweight (body mass index: 25-29.9 kg/m2), and obese (body mass index ⩽ 30 kg/m2). RESULTS: Median age at surgery was 65 years (range: 27-84 years), of which 207 (72.6%) were males. Patients with the lowest body mass index and the obese patients seemed to have a higher frequency of minor complications. Anastomotic leakage occurred in less than 10% of the patients and was equally distributed across the groups as was the other major complications. There were no differences in the 1-, 2-, or 5-year survival rates between the four body mass index groups after adjustment for possible confounders. Five-year survival rates for the four body mass index groups were 31.8%, 28.7%, 27.9%, and 26.1%, respectively. CONCLUSION: Body mass index over 30 or under 18.5 does not seem to affect survival rates or the presence of serious postoperative complications following esophagectomy in patients with esophageal and gastro-esophageal-junction cancers not receiving neoadjuvant oncological treatment.

Diagnostic laparoscopy and ultrasonography for colorectal liver metastases.

BACKGROUND AND AIMS: To evaluate diagnostic laparoscopy (DL) and laparoscopic ultrasonography (LUS) in the diagnostic workout of patients with colorectal liver metastases, who were considered to have resectable disease after multi detector computed tomography (MDCT). MATERIAL AND METHODS: The medical records of 45 patients, 22M/23F, mean age 62.0 (+/-10.6), who were considered to have resectable liver metastases after CT-scan, were analysed. RESULTS: DL and LUS could not be performed in 7 patients (16%) because of adhesions. Unresectable disease was detected by DL in 3 patients (7%), in all cases due to carcinosis. Additional lesions in the liver were detected by DL in 2 cases (4%), none of these making the patient unresectable. LUS showed additional lesions in 3 patients (7%), which in one case (2%) made the patient unresectable. None of the patients in the present study experienced adverse effects to DL or LUS. CONCLUSION: DL and LUS, due to the low efficacy with regard to avoid unnecessary laparotomies and the relative high failure rate because of adhesions, should not be a routine part of the diagnostic work out in patients with colo-rectal liver metastases.

Simultaneous colorectal and liver resections for synchronous colorectal metastases.

BACKGROUND: The surgical strategy for the treatment of colorectal cancer and synchronous hepatic metastases remains controversial. Many surgeons fear anastomotic leakage and intraperitoneal abscesses when performing a one-step procedure. They prefer a two-step procedure with a liver resection 2 to 3 months after resection of the colorectal primary lesion. SUBJECTS AND METHODS: We analysed medical records from April 1994 to April 2002 for a total of 42 patients with colorectal cancer and synchronous liver metastases who underwent simultaneous liver and colorectal resections with a primary anastomosis. Special attention was paid to data on surgical procedures, postoperative morbidity, and mortality. RESULTS: Forty-two patients, 24 men and 18 women, were studied. Median operating time was 6.50 hours (3.75-11.0 hours), and median blood loss was 1522 ml (range 288 to 5650 ml). Postoperative complications included pleural effusion in 4 patients, ileus in 3, anastomotic leakage in 2, intraperitoneal pelvic abscesses in 1, pneumonia in 1, bile leakage in 1, atelectasis in 1, and wound infection in 1. There was no perioperative mortality. CONCLUSION: Simultaneous colorectal resection with a primary anastomosis and hepatectomy for synchronous liver metastases is considered a safe procedure.

Percutaneous cholecystostomy is an effective definitive treatment option for acute acalculous cholecystitis.

AIMS: Acute acalculous cholecystitis can be treated with percutaneous cholecystostomy in critically ill patients unfit for surgery. However, the evidence on the outcome is sparse. We conducted a retrospective analysis of acute acalculous cholecystitis patients treated with percutaneous cholecystostomy during a 10-year study period. METHODS: An observational study of 56 consecutive patients treated with percutaneous cholecystostomy for acute acalculous cholecystitis was conducted in the period from 1 June 2002 to 31 May 2012. All data were obtained by review of medical records. RESULTS: A total of 56 consecutive patients were treated with percutaneous cholecystostomy for acute acalculous cholecystitis. Six patients (10.7%) died within 30 days after the procedure. Percutaneous cholecystostomy could serve as a definitive treatment option in 45 patients (80.4%), whereas 1 patient (1.8%) required cholecystectomy due to recurrence of cholecystitis. Four patients (7.1%) were treated with percutaneous cholecystostomy as a bridging procedure to subsequent elective laparoscopic cholecystectomy within a median of 8.8 months (range: 7.7-33.4 months). There was no significant difference in the risk of cholecystitis recurrence between patients with (6/37) and without (2/3) contrast passage to the duodenum on cholangiography (p = 0.096). CONCLUSION: Percutaneous cholecystostomy is successful as a definitive treatment option in the majority of patients with acute acalculous cholecystitis. It is associated with a low rate of mortality and subsequent cholecystectomy.

Responses to noradrenaline in human subcutaneous resistance arteries are mediated by both alpha 1- and alpha 2-adrenoceptors.

1. In vitro experiments in a microvascular myograph were designed to characterize postjunctional alpha-adrenoceptors of human subcutaneous resistance arteries (normalised internal diameter 143-313 microns). 2. Both the alpha 1-selective agonist phenylephrine in the presence of 0.3 microM yohimbine and the alpha 2-selective agonist B-HT 933 in the presence of 0.3 microM prazosin elicited prominent and concentration-dependent contractions. The maximum response to phenylephrine and B-HT 933 was not different from the response to high K physiological salt solution (125 mM K+), and the pD2 values (-log EC50) were 5.90 and 6.11, respectively. 3. In the presence of the alpha 2-selective antagonist yohimbine (0.3 microM), the alpha 1-selective antagonist prazosin competitively antagonised the responses to phenylephrine; the pA2 of prazosin for the receptor which mediated the response to phenylephrine was 8.41. 4. Blockade of either alpha 2-adrenoceptors with 0.1 microM yohimbine or alpha 1-adrenoceptors with 0.1 microM prazosin caused shifts to the right of the noradrenaline concentration-response curves and the shifts in pD2 were 0.69 and 0.61, respectively. The combination of the two antagonists at the above-mentioned concentrations caused a marked, parallel shift to the right of the noradrenaline concentration-response curve, the shift of the pD2 was 2.68. 5. These results suggest that activation of both alpha 1- and alpha 2-adrenoceptors produces contractions in human subcutaneous resistance arteries, and that responses to noradrenaline in these vessels are mediated by both alpha-adrenoceptor subtypes.

Effects of short-chain fatty acids on in vitro bacterial growth of Bacteroides fragilis and Escherichia coli.

Short-chain fatty acids (SCFA) are produced in the large bowel of nonruminant mammals by bacterial anaerobic fermentation. The aim of the present study was to investigate the effects of SCFA on the in vitro growth of Bacteroides fragilis and Escherichia coli. B. fragilis and E. coli isolated from fresh human clinical samples and a reference strain for each species were incubated in a meat infusion broth with increasing amounts of SCFA and grown under anaerobic conditions at a temperature of 37 degrees C. Bacterial growth was estimated by spectrophotometry. Rate of growth was calculated from the logarithmic growth phase. SCFA, in concentrations normally found in the human colon, had a significant (p<0.01) inhibitory effect of the in vitro growth rate for E. coli, while they were without effect on the in vitro growth rate of B. fragilis. It may be concluded that under in vitro conditions SCFA had growth-inhibitory effects on E. coli, while they had no effect on B. fragilis.

Short-chain fatty acid enemas stimulate plasminogen activator inhibitor-1 after abdominal aortic graft surgery: a double-blinded, placebo-controlled study.

Colonic ischaemia may complicate aortic graft surgery with high mortality from associated colonic necrosis. Loss of the mucosal barrier function due to ischaemia may promote translocation of endotoxins with secondary systemic disseminated coagulation leading to multiple organ failure. Short-chain fatty acids (SCFAs) stimulate the microcirculation in the human rectum. The aim of this study was to investigate whether SCFA enemas influence systemic endotoxinaemia and fibrinolytic activity during and after elective aortic graft surgery for arteriosclerosis. Thirty-two patients were randomized to SCFA or placebo enemas twice daily from the day before surgery to 7 days after. Blood samples for endotoxin, plasminogen activator inhibitor-1 (PAI-1) activity, tissue-type plasminogen activator (t-PA) antigen, and cross-linked fibrin degradation products (XL-FDP) were drawn before, during, and 7 days after surgery. Four patients, two in each treatment group, developed postoperative endotoxinaemia. PAI-1 was significantly higher on days 2 and 4 in SCFA-treated patients, whereas t-PA was comparable Petween the groups. During the postoperative course, a progressive and near-identical XL-FDP increase was found in the two groups. In elective aortic graft surgery for arteriosclerosis, SCFA enemas likely stimulate systemic PAI-1 activity by promoting colonic tissue reperfusion following aortic unclamping. Endotoxinaemia and fibrinolytic shutdown are uncommon findings.

[Alternative treatment forms used by patients with muscular atrophy. A questionnaire study of the use of alternative treatment by 345 patients with muscular atrophy]. / Muskelsvindramtes brug af alternativ behandling. En enqueteundersøgelse af 345 muskelsvindramtes brug af alternative behandlinger.

An investigation about the use of alternative treatment by a group of persons with muscular atrophy revealed that 24% had employed alternative treatment during the period 1.1.1983-1.4.1986. This is probably a greater proportion than in the Danish population as a whole. Patients with muscular atrophy were subdivided into three groups on the basis of their ability to function in daily life. No significant connection was found between the degree of loss of function and alternative treatment as regards the frequencies of alternative treatment and the numbers of treatments employed. A given form form of treatment was most frequently recommended by an unaffected acquaintance. Physical forms of treatment such as zone therapy and chiropractics were employed more frequently than chemical forms of therapy. Less than half of the patients were satisfied with the results of treatment. Treatment was often concluded in a negative manner. Patients considered that, in contrast to the alternative therapist, the doctor performs the best and most thorough examination and provides them with the best information about their condition.

[Referral to a department of medical gastroenterology. A study of the content of the referral letter and the reasons for referral]. / Henvisning til en medicinsk gastroenterologisk afdeling. En undersøgelse af henvisningernes indhold og henvisningsårsager.

Knowledge concerning factors that affect referrals of patients by general practitioners to hospitals is important in view of optimal utilization of the resources. Out of 108 referrals from general practitioners to a medical department of gastroenterology, information about the medical history was insufficient in about half the cases, and in 3/4 of the cases information about medicine was absent. Information about allergy and social conditions was found in only a few cases. The reason for referral was in most cases to establish a diagnosis and treatment. It is concluded, that if functions in a medical department of gastroenterology are to be moved to the general practitioners, more education in diagnostic procedures and treatment is needed. Further investigations are needed to solve these problems.

Radiofrequency ablation of colorectal liver metastases: long-term survival.

PURPOSE: To evaluate the results of radiofrequency ablation (RFA) therapy with regard to long-term survival and rate of complications in patients with liver metastases from colorectal carcinoma. MATERIAL AND METHODS: A total of 102 patients were included and treated with RFA. In 100 patients, resection was not possible; two patients refused surgery. The patients had a total of 332 colorectal liver metastases. Pre- and post-treatment evaluation was performed with contrast-enhanced computed tomography. Survival from time of diagnosis of liver metastases was calculated by Kaplan-Meier analysis. Complications were recorded as minor or major in accordance with the definitions of the Society for Cardiovascular and Interventional Radiology. RESULTS: Estimated median survival from time of diagnosis of liver metastases was 52 months (95% CI 34-82). Estimated 1-, 2-, 3-, 4-, and 5-year survival was 96%, 79%, 64%, 52%, and 44%, respectively. Minor complications were recorded following seven RFA treatments (4.0%) and major complications following 12 RFA treatments (6.9%). CONCLUSION: RFA is an effective method to treat liver metastases from colorectal carcinoma. Survival is improved and comparable with survival following surgical resection. The rate of complications is low.

Differential distribution of postjunctional alpha 2 adrenoceptors in human omental small arteries.

A pharmacologic characterization of the postjunctional alpha adrenoceptors of human omental small arteries was performed using a microvascular myograph. Both the alpha 1-selective agonist phenylephrine in the presence of yohimbine (0.3 microM, alpha 2-selective antagonist) and the alpha 2-selective agonist B-HT 933 in the presence of prazosin (0.3 microM, alpha 1-selective antagonist) evoked strong vasoconstriction. The responses to phenylephrine were competitively antagonized by prazosin, whereas the responses to B-HT 933 were competitively antagonized by yohimbine; the pA2-values were 9.24 and 8.34, respectively. An inverse relationship of the maximum response to B-HT 933 (r = -0.53; p less than 0.001), but not to phenylephrine or to norepinephrine (NE), against artery caliber was observed. The shifts of the NE concentration-response curves caused by yohimbine (0.1 microM) were more marked in the smaller rather than the larger vessels (r = -0.71; p less than 0.01), whereas the opposite was observed using 0.1 microM prazosin (r = 0.84; p less than 0.001). These data suggest that both alpha 1 and alpha 2 adrenoceptors are present in the human omental small arteries, but whereas postjunctional alpha 2 adrenoceptors appear to be located predominantly in the resistance arteries, postjunctional alpha 1 adrenoceptors appear to be distributed evenly along the arterial tree.

Short chain fatty acids relax isolated resistance arteries from the human ileum by a mechanism dependent on anion-exchange.

Ileal resistance arteries (internal diameter 184-337 microns) were discussed out under microscope and mounted in a microvascular myograph for isometric tension recording. Experiments were designed to test compounds trophic to the small intestine, namely, epidermal growth factor, glutamine and the three short chain fatty acids, acetic, propionic and butyric acid, for effects on vascular tone. Glutamine in concentrations up to 30 mM and epidermal growth factor in concentrations up to 1 microM had no contractile or relaxant effects on the resistance arteries. The three short chain fatty acids alone and in combination, however, caused a concentration-dependent (range 0.1-30 mM) relaxation of resistance arteries precontracted with 50 mM KCl. This relaxant effect was significantly inhibited by the presence of the anion-exchange inhibitor 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid whereas it was unaffected by removal of the endothelium, presence of indomethacin, propranolol or phentolamine. These data suggest that the trophic effects of glutamine and epidermal growth factor on the small intestinal mucosa cannot be explained through actions on the resistance vasculature. In contrast, the relaxant effect of short chain fatty acid on resistance arteries in vitro suggests that these compounds may be able to improve the microcirculation in vivo. An improved microcirculation will, all things considered, facilitate the growth of the small intestinal mucosa.

Heterogeneity of postjunctional alpha-adrenoceptors in isolated mesenteric resistance arteries from rats, rabbits, pigs, and humans.

Mesenteric resistance arteries (internal diameter 174-337 microns) from rats, rabbits, pigs, and humans were isolated and mounted in a myograph. In all preparations, phenylephrine (alpha 1-adrenoceptor agonist) evoked concentration-dependent contractions that were antagonized by prazosin (alpha 1-adrenoceptor antagonist). B-HT 933 (alpha 2-adrenoceptor agonist), however, did not evoke contractions in any rat or rabbit vessels. In contrast, this agonist elicited contractions in some (five of 15) porcine and all (18) human vessels; in the vessels responsive to B-HT 933, the maximum responses amounted to 53 +/- 7 and 79 +/- 6%, respectively, of the responses to high potassium. The affinities of yohimbine (alpha 2-adrenoceptor antagonist) for the receptors mediating responses to B-HT 933 were 7.46 +/- 0.13 (pKB) and 7.57 +/- 0.10 (pA2), respectively. Prazosin (10(-8) M) antagonized the responses to norepinephrine in all preparations, whereas yohimbine (10(-7) M) caused significant inhibition of these responses in human vessels only; moreover, the inhibition in these vessels of the responses to norepinephrine caused by the combination of these two antagonists was greater than the antagonism caused by either antagonist alone. These results suggest the presence of postjunctional alpha 1-adrenoceptors that are involved in responses to norepinephrine in mesenteric resistance arteries from all species examined. Functional, postjunctional alpha 2-adrenoceptors appear to be present in porcine and human vessels, but this receptor seems to be involved in responses to norepinephrine in human vessels only.