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.

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.

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.

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.

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.

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.

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.

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.

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.

Short-chain fatty acids stimulate mucosal cell proliferation in the closed human rectum after Hartmann's procedure.

Hartmann's procedure in humans results in a closed rectum deprived of its natural short-chain fatty acid source. This induces atrophy of the entire rectal wall. Ki-67 is a monoclonal antibody directed towards proteins in the cell nucleus that are present only during cell proliferation. This study investigated the effects of short-chain fatty acids on mucosal cell proliferation in the human rectum after Hartmann's procedure by means of Ki-67. Eight patients in whom Hartmann's procedure was performed were treated with placebo and then short-chain fatty acids for 14 days. Biopsies specimens were taken from the rectum before and after treatment; these were prepared with Ki-67 and labeling index was determined. The treatment was found significantly to increase proliferative activity in the rectal mucosa (P<0.01); the increase was principally in the middle (P<0.01) and upper crypt (P<0.05) compartments.

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.

Effect of moderate exercise on blood flow in the gastrointestinal tract in trained conscious miniature swine.

AIM: To examine how moderate exercise affects the blood flow in the gastrointestinal tract. MATERIALS AND METHODS: Twelve miniature swine weighing 38-43 kg were used. All animals were trained on a cardiac exercise treadmill. Blood flow measurements were done on conscious animals using labeled microspheres with a diameter of 16.5 +/- 0.1 (SD) microm. The first flow was measured while the animal was awake and resting, the second flow after 15 min of exercise, the third flow after 30 min of rest. RESULTS: Flow in the oesophagus at rest was 19.5 +/- 1.3 (SEM) ml/min/100 g. During exercise the flow decreased to 13.3 +/- 1.2 (SEM) ml/min/100 g (ns). After 30 min of rest the flow was 9.9 +/- 1.2 (SEM) ml/min/100 g (p < 0.05 when comparing the flow before and after exercise). Flow in the cardia at rest was 23.1 +/- 1.3 (SEM) ml/min/100 g. During exercise the flow decreased to 14.0 +/- 1.2 (SEM) ml/min/100 g (p < 0.05). After 30 min of rest the flow was 15.0 +/- 1.2 (SEM) ml/min/100 g. Flow in the pylorus at rest was 38.9 +/- 1.1 (SEM) ml/min/100 g. During exercise the flow decreased to 24.6 +/- 1.1 (SEM) ml/min/100 g (p < 0.01). After 30 min of rest the flow was 26.9 +/- 1.2 (SEM) ml/min/100 g. Blood flow in the small and large intestine was mainly unaffected by moderate exercise. CONCLUSION: Under moderate exercise, blood flow in the upper part of the gastrointestinal tract declines while it is mainly unaffected in the duodenum, small and large intestine.

Aseptic laparoscopic colon resection with intraabdominal anastomosis. An experimental study in pigs.

BACKGROUND: We evaluated a new aseptic method for laparoscopic left colon resection in terms of technical feasibility and outcome. METHODS: Ten pigs were operated on under general anesthesia. Pre- and postoperative body weight, stools, behavior, and need for analgesics were recorded. Fourteen days later, the animals were killed. At autopsy, the degree of intraabdominal adhesions was noted. The anastomoses were sent for histological examination. The entire procedure was performed intracorporeally, and no antibiotics were given. After division of the mesocolon, the segment to be resected was invaginated down through the colon. This was facilitated by a custom-made instrument that was introduced into the bowel via the anus; it consisted of a pull-out device and a modified diathermy wire. The anastomosis was completed at the invagination fold by a row of hernia staples that were covered by an interrupted suture. Then the invaginated bowel was transected by the diathermy wire and delivered through the anus. RESULTS: One animal was killed before completion of the operation because of a colonic perforation. The remaining nine animals had an uneventful and rapid recovery. They ate from the 1st postoperative day and gained weight rapidly. Stools were normal after 2 days (median), and normal behaviour was noted in all animals from the 1st postoperative day. At the postmortem examination, intraabdominal adhesions were observed in two animals. In one case, the adhesions extended from a hematoma in the mesentery to the abdominal wall. There were no adhesions to the anastomosis or the colon. In the other case, the anastomosis adhered to the right uterine tube and a loop of small intestines. CONCLUSIONS: The method is technically feasible, but a modification is suggested for cases where the invagination is impossible. Recovery after the operation is rapid.

Validation of a new transit time ultrasound flowmeter for measuring blood flow in colonic mesenteric arteries.

OBJECTIVE: To validate a transit time ultrasound flowmeter (CardioMed CM 4000) for measuring blood flow in isolated colonic mesenteric arteries. DESIGN: Experimental and clinical study. SETTING: Teaching hospital, Denmark. ANIMALS AND SUBJECTS: One female pig, and 6 patients being operated on for carcinoma of the sigmoid colon and rectum. INTERVENTIONS: Volume blood flow measured by Cardiomed CM 4000 and pump withdrawal flow recordings. MAIN OUTCOME MEASURES: Correlation between the two methods. RESULTS: There was good agreement between transit time flow recordings and pump withdrawal flow recordings (correlation coefficient of 1.0). Of the differences between the two methods, 95% were between -0.16 ml min(-1) and 1.29 ml min(-1), mean 0.57 ml min(-1), or (in percentages) 105, 95% lying between 97-115. There was also good reproducibility in transit time flow recordings, the mean difference between repeated measurements being 0.06 ml min(-1), 95% lying between -0.66 ml min(-1) and 0.78 ml min(-1). CONCLUSION: Ultrasound transit time flow recordings gave precise measurements of blood flow in isolated colonic mesenteric arteries.

The role of [Ca2+]i, membrane potential and pHi in the relaxation of rat mesenteric arteries to hyperosmolar acetate.

In vitro both acetate and hyperosmolarity cause vasodilation, which could be physiologically important during food ingestion and during peritoneal dialysis. The purpose of this study was to investigate the role of the intracellular calcium concentration ([Ca2+]i, measured with fura-2), membrane potential (measured with glass microelectrodes) and intracellular pH [pHi, measured with bis-carboxyethylcarboxyfluorescein (BCECF)] in the vasodilation. Hyperosmolar sodium acetate (30 mM) concentration dependently relaxed noradrenaline-precontracted arteries. This response was associated with hyperpolarization and a fall in [Ca2+]i. In arteries precontracted with 50 mM K+ the relaxation was associated with a decrease of [Ca2+]i but no change in membrane potential. Isoosmolar sodium acetate neither relaxed or affect [Ca2+]i of K+-precontracted arteries, but induced a small relaxation with no reduction in [Ca2+]i in noradrenaline-precontracted arteries. Hyperosmolar acetate caused a transient reduction of pHi that was unrelated to relaxation. It is concluded that the mechanisms responsible for the relaxation to hyperosmolar acetate involve a decrease of [Ca2+]i, which is only partly explained by hyperpolarization and probably a decrease in the sensitivity of the contractile proteins to [Ca2+]i. pHi seems not to play a role in these effects.

Transmural trophic effect of short chain fatty acid infusions on atrophic, defunctioned rat colon.

PURPOSE: This study was designed to investigate and quantify trophic alterations in the defunctioned, atrophic rat colon after short chain fatty acid (SCFA) treatment was administered in a clinically relevant way. METHODS: Diverting colostomy with exclusion of distal colon was performed on adult female rats (58), and treatment was started four weeks later. Enemas of either a SCFA solution of sodium-acetate, sodium-propionate and sodium-butyrate (concentration, 780 mM), or isotonic saline (placebo) were instilled through the anus into the defunctioned colon. This was done twice daily for 7 or 14 days before death. RESULTS: After SCFA instillation for 14 days, the colonic wet weight was 18 percent higher compared with placebo (P < 0.01), and there was a similarly significant difference in dry weight (P < 0.05). Using stereologic assessment to determine the histologic composition of defunctioned colon, we found significant increases among SCFA-treated rats in the weight of the mucose (P < 0.05), the submucosa (P < 0.05), and the muscularis propria (P < 0.05) and a 30 percent increase in the mucosal surface area compared with placebo-treated in the mucosal surface area compared with placebo-treated rats (P < 0.05). Measurements of breaking strength and hydroxyproline content showed no differences between treatment groups. CONCLUSIONS: SCFA enemas have a transmural trophic effect and preserve mucosal surface area of defunctioned and atrophic colon in rats.