Histopathological growth patterns of colorectal liver metastasis exhibit little heterogeneity and can be determined with a high diagnostic accuracy.

Colorectal liver metastases (CRLM) exhibit distinct histopathological growth patterns (HGPs) that are indicative of prognosis following surgical treatment. This study aims to assess the reliability and replicability of this histological biomarker. Within and between metastasis HGP concordance was analysed in patients who underwent surgery for CRLM. An independent cohort was used for external validation. Within metastasis concordance was assessed in CRLM with ≥ 2 tissue blocks. Similarly, concordance amongst multiple metastases was determined in patients with ≥ 2 resected CRLM. Diagnostic accuracy [expressed in area under the curve (AUC)] was compared by number of blocks and number of metastases scored. Interobserver agreement (Cohen's k) compared to the gold standard was determined for a pathologist and a PhD candidate without experience in HGP assessment after one and two training sessions. Both the within (95%, n = 825) and the between metastasis (90%, n = 363) HGP concordance was high. These results could be replicated in the external validation cohort with a within and between metastasis concordance of 97% and 94%, respectively. Diagnostic accuracy improved when scoring 2 versus 1 blocks(s) or CRLM (AUC = 95.9 vs. 97.7 [p = 0.039] and AUC = 96.5 vs. 93.3 [p = 0.026], respectively), but not when scoring 3 versus 2 blocks or CRLM (both p > 0.2). After two training sessions the interobserver agreement for both the pathologist and the PhD candidate were excellent (k = 0.953 and k = 0.951, respectively). The histopathological growth patterns of colorectal liver metastasis exhibit little heterogeneity and can be determined with a high diagnostic accuracy, making them a reliable and replicable histological biomarker.

Randomized clinical trial of stapler hepatectomy versus LigaSure™ transection in elective hepatic resection.

BACKGROUND: Previous studies have demonstrated stapler hepatectomy and use of various energy devices to be safe alternatives to the clamp-crushing technique in elective hepatic resection. In this randomized trial, the effectiveness and safety of stapler hepatectomy were compared with those of parenchymal transection with the LigaSure™ vessel sealing system. METHOD: Patients scheduled for elective liver resection at two tertiary-care centres were randomized during surgery to stapler hepatectomy or transection with the LigaSure™ device. Total intraoperative blood loss was the primary efficacy endpoint. Transection time, duration of operation, perioperative complications and length of hospital stay were recorded as secondary endpoints. RESULTS: A total of 138 patients were analysed, 69 in the LigaSure™ and 69 in the stapler hepatectomy group. Baseline characteristics were well balanced between the groups. Mean intraoperative blood loss was significantly higher in the LigaSure™ group than the stapler hepatectomy group: 1101 (95 per cent c.i. 915 to 1287) versus 961 (752 to 1170) ml (P = 0·028). The parenchymal transection time was significantly shorter in the stapler group (P = 0·005), as was the total duration of operation (P = 0·027). Surgical morbidity did not differ between the groups, nor did the grade of complications. CONCLUSION: Stapler hepatectomy was associated with reduced blood loss and a shorter duration of operation than the LigaSure™ device for parenchymal transection in elective partial hepatectomy. Registration number: NCT01858987 (http://www.clinicaltrials.gov).

Circulating tumour cells and outcome in non-metastatic colorectal cancer: a prospective study.

BACKGROUND: Circulating tumour cells (CTC) in the blood have been accepted as a prognostic marker in patients with metastatic colorectal cancer (CRC). Only limited data exist on the prognostic impact of CTC in patients with early stage CRC using standardised detection assays. The aim of this study was to elucidate the role of CTC in patients with non-metastatic CRC. METHODS: A total of 287 patients with potentially curable CRC were enrolled, including 239 patients with UICC stage I-III. CTC were measured in the blood using the CellSearch system preoperatively and on postoperative days 3 and 7. The complete patient group (UICC I-IV) and the non-metastatic cohort (UICC I-III) were analysed independently. Patients were followed for 28 (0-53) months. Prognostic factors for overall and progression-free survival were analysed using univariate and multivariate analyses. RESULTS: CTC were detected more frequently in patients with metastatic disease. No clinicopathological variables were associated with CTC detection in non-metastatic patients. CTC detection (⩾1 CTC per 7.5 ml blood) in the blood was significantly associated with worse overall survival (49.8 vs 38.4 months; P<0.001) in the non-metastatic group (UICC I-III), as well as in the complete cohort (48.4 vs 33.6 months; P<0.001). On multivariate analysis CTC were the strongest prognostic factor in non-metastatic patients (hazard ratio (HR) 5.5; 95% confidence interval (CI) 2.3-13.6) as well as in the entire study group (HR 5.6; 95% CI 2.6-12.0). CONCLUSIONS: Preoperative CTC detection is a strong and independent prognostic marker in non-metastatic CRC.

[Lichtenstein's hernia repair]. / Lichtenstein's Hernia Repair.

AIM: Lichtenstein's hernia repair (LHR) is presented as a technically feasible procedure for inguinal hernia. INDICATION: LHR is a standard procedure for open mesh techniques with very good postoperative results. METHOD: We demonstrate an LHR step by step with preservation of the iliohypogastricus and ilioinguinalis nerves. CONCLUSION: LHR is a technically feasible and safe procedure which should have a firm place in a general surgical education.

Randomized clinical trial of stapler versus clamp-crushing transection in elective liver resection.

BACKGROUND: Various devices have been developed to facilitate liver transection and reduce blood loss in liver resections. None of these has proven superiority compared with the classical clamp-crushing technique. This randomized clinical trial compared the effectiveness and safety of stapler transection with that of clamp-crushing during open liver resection. METHODS: Patients admitted for elective open liver resection between January 2010 and October 2011 were assigned randomly to stapler transection or the clamp-crushing technique. The primary endpoint was the total amount of intraoperative blood loss. Secondary endpoints included transection time, duration of operation, complication rates and resection margins. RESULTS: A total of 130 patients were enrolled, 65 to clamp-crushing and 65 to stapler transection. There was no difference between groups in total intraoperative blood loss: median (i.q.r.) 1050 (525-1650) versus 925 (450-1425) ml respectively (P = 0·279). The difference in total intraoperative blood loss normalized to the transection surface area was not statistically significant (P = 0·092). Blood loss during parenchymal transection was significantly lower in the stapler transection group (P = 0·002), as were the parenchymal transection time (mean(s.d.) 30(21) versus 9(7) min for clamp-crushing and stapler transection groups respectively; P < 0·001) and total duration of operation (mean(s.d.) 221(86) versus 190(85) min; P = 0·047). There were no significant differences in postoperative morbidity (P = 0·863) or mortality (P = 0·684) between groups. CONCLUSION: Stapler transection is a safe technique but does not reduce intraoperative blood loss in elective liver resection compared with the clamp-crushing technique. REGISTRATION NUMBER: NCT01049607 (http://www.clinicaltrials.gov).

Randomized clinical trial on the effect of coffee on postoperative ileus following elective colectomy.

BACKGROUND: Postoperative ileus is a common problem after abdominal surgery. It was postulated that coffee intake would decrease postoperative ileus after colectomy. METHODS: This was a multicentre parallel open-label randomized trial. Patients with malignant or benign disease undergoing elective open or laparoscopic colectomy were assigned randomly before surgery to receive either coffee or water after the procedure (100 ml three times daily). The primary endpoint was time to first bowel movement; secondary endpoints were time to first flatus, time to tolerance of solid food, length of hospital stay and perioperative morbidity. RESULTS: A total of 80 patients were randomized, 40 to each group. One patient in the water arm was excluded owing to a change in surgical procedure. Patient characteristics were similar in both groups. In intention-to-treat analysis, the time to the first bowel movement was significantly shorter in the coffee arm than in the water arm (mean(s.d.) 60·4(21·3) versus 74·0(21·6) h; P = 0·006). The time to tolerance of solid food (49·2(21·3) versus 55·8(30·0) h; P = 0·276) and time to first flatus (40·6(16·1) versus 46·4(20·1) h; P = 0·214) showed a similar trend, but the differences were not significant. Length of hospital stay (10·8(4·4) versus 11·3(4·5) days; P = 0·497) and morbidity (8 of 40 versus 10 of 39 patients; P = 0·550) were comparable in the two groups. CONCLUSION: Coffee consumption after colectomy was safe and was associated with a reduced time to first bowel action.

A randomised controlled pilot trial to evaluate and optimize the use of anti-platelet agents in the perioperative management in patients undergoing general and abdominal surgery--the APAP trial (ISRCTN45810007).

PURPOSE: Surgeons are increasingly confronted by patients on long-term low-dose acetylsalicylic acid (ASA). However, owing to a lack of evidence-based data, a widely accepted consensus on the perioperative management of these patients in the setting of non-cardiac surgery has not yet been reached. Primary objective was to evaluate the safety of continuous versus discontinuous use of ASA in the perioperative period in elective general or abdominal surgery. METHODS: Fifty-two patients undergoing elective cholecystectomy, inguinal hernia repair or colonic/colorectal surgery were recruited to this pilot study. According to cardiological evaluation, non-high-risk patients who were on long-term treatment with low-dose ASA were eligible for inclusion. Patients were allocated randomly to continuous use of ASA or discontinuation of ASA intake for 5 days before until 5 days after surgery. The primary outcome was the incidence of major haemorrhagic and thromboembolic complications within 30 days after surgery. RESULTS: A total of 26 patients were allocated to each study group. One patient (3.8%) in the ASA continuation group required re-operation due to post-operative haemorrhage. In neither study group, further bleeding complications occurred. No clinically apparent thromboembolic events were reported in the ASA continuation and the ASA discontinuation group. Furthermore, there were no significant differences between both study groups in the secondary endpoints. CONCLUSIONS: Perioperative intake of ASA does not seem to influence the incidence of severe bleeding in non-high-risk patients undergoing elective general or abdominal surgery. Further, adequately powered trials are required to confirm the findings of this study.

Postoperative course and clinical significance of biochemical blood tests following hepatic resection.

BACKGROUND: Hepatic resection continues to be associated with substantial morbidity. Although biochemical tests are important for the early diagnosis of complications, there is limited information on their postoperative changes in relation to outcome in patients with surgery-related morbidity. METHODS: A total of 835 consecutive patients underwent hepatic resection between January 2002 and January 2008. Biochemical blood tests were assessed before, and 1, 3, 5 and 7 days after surgery. Analyses were stratified according to the extent of resection (3 or fewer versus more than 3 segments). RESULTS: A total of 451 patients (54·0 per cent) underwent resection of three or fewer anatomical segments; resection of more than three segments was performed in 384 (46·0 per cent). Surgery-related morbidity was documented in 258 patients (30·9 per cent) and occurred more frequently in patients who had a major resection (P = 0·001). Serum bilirubin and international normalized ratio as measures of serial hepatic function differed significantly depending on the extent of resection. Furthermore, they were significantly affected in patients with complications, irrespective of the extent of resection. The extent of resection had, however, little impact on renal function and haemoglobin levels. Surgery-related morbidity caused an increase in C-reactive protein levels only after a minor resection. CONCLUSION: Biochemical data may help to recognize surgery-related complications early during the postoperative course, and serve as the basis for the definition of complications after hepatic resection.

Leucocyte-depleted blood transfusion is an independent predictor of surgical morbidity in patients undergoing elective colon cancer surgery-a single-center analysis of 531 patients.

BACKGROUND: Leukocyte-depleted packed red blood cells (PRBC) were introduced to reduce potential immunomodulatory effects and transfusion-associated morbidity. It has, however, remained unclear, if leucocyte depletion prevents negative side effects of blood transfusion. The aim of this analysis was to examine the effects of leukocyte-depleted PRBC on surgical morbidity after elective colon cancer surgery. METHODS: Data were prospectively collected from 531 consecutive patients undergoing elective colon cancer surgery at a single high-volume center (University Hospital) from 2002 to 2008. Potentially predictive factors for surgical morbidity were tested on univariate and multivariate analysis. RESULTS: A total of 531 patients with colon cancer were included. A curative (R0) resection was performed in 497 patients (94%). The mortality rate, overall morbidity rate, and surgical morbidity rate were 1.1, 33, and 21%, respectively. Some 135 patients (25%) received perioperative transfusion of PRBCs. On multivariate analysis age (odds ratio [OR] 1.04, 95% confidence interval [95% CI] 1.02-1.06; P = 0.001), BMI (OR 1.08, 95% CI 1.03-1.13; P = 0.003), and PRBC transfusion (2.4, 1.41-4.11; P = 0.001) were revealed as independent predictors of surgical morbidity. The risk of surgical complications increased continuously with the amount of transfused PRBCs. The adverse impact of PRBC transfusion was neither restricted to the timepoint of transfusion (intraoperative or postoperative), nor to the kind of complication (infectious vs noninfectious complication). CONCLUSION: Perioperative transfusion of leukocyte-depleted PRBCs has a significantly negative effect on surgical morbidity of patients undergoing elective colon cancer surgery. The use of perioperative blood transfusions in these patients should be avoided, whenever possible.

Emergency liver transplantation after umbilical hernia repair: a case report.

We report a rare case of acute liver failure due to embolization of the liver after an umbilical hernia repair in a patient with Child B liver cirrhosis and status posttransjugular intrahepatic portosystemic shunt (TIPSS). This patient initially presented with a symptomatic umbilical hernia. His umbilical vein was open (Cruveilhier-Baumgarten syndrome). After hernia repair the patient developed thrombosis of the umbilical vein with consequent partial embolization to, and acute failure of, the liver. The patient underwent successful emergency liver transplantation. This disease needs close collaboration among surgeons, gastroenterologists, hepatologists, radiologists, nutritionists, and transplant teams to establish an effective treatment plan.

A single center experience of combined liver kidney transplantation.

With advancements in the operative techniques, patient survival following liver transplantation (LTx) has increased substantially. This has led to the acceleration of pre-existing kidney disease because of immunosuppressive nephrotoxicity making additional kidney transplantation (KTx) inevitable. On the other hand, in a growing number of patients on the waiting list to receive liver, long waiting time has resulted in adverse effect of decompensated liver on the kidney function. During the last two decades, the transplant community has considered combined liver kidney transplantation (CLKTx) to overcome this problem. The aim of our study is to present an overview of our experience as well as a review of the literature in CLKTx and to discuss the controversy in this regard. All performed CLKTx (n = 22) at our institution as well as all available reported case series focusing on CLKTx are extracted. The references of the manuscripts were cross-checked to implement further articles into the review. The analyzed parameters include demographic data, indication for LTx and KTx, duration on the waiting list, Model for End-Stage Liver Disease (MELD) score, Child-Turcotte-Pugh (CTP) score, immunosuppressive regimen, post-transplant complications, graft and patient survival, and cause of death. From 1988 to 2009, a total of 22 CLKTx were performed at our institution. The median age of the patients at the time of CLKTx was 44.8 (range: 4.5-58.3 yr). The indications for LTx were liver cirrhosis, hyperoxaluria type 1, polycystic liver disease, primary or secondary sclerosing cholangitis, malignant hepatic epithelioid hemangioendothelioma, cystinosis, and congenital biliary fibrosis. The KTx indications were end-stage renal disease of various causes, hyperoxaluria type 1, polycystic kidney disease, and cystinosis. The mean follow-up duration for CLKTx patients were 4.6 +/- 3.5 yr (range: 0.5-12 yr). Overall, the most important encountered complications were sepsis (n = 8), liver failure leading to retransplantation (n = 4), liver rejection (n = 3), and kidney rejection (n = 1). The overall patient survival rate was 80%. Review of the literature showed that from 1984 to 2008, 3536 CLKTx cases were reported. The main indications for CLKTx were oxalosis of both organs, liver cirrhosis and chronic renal failure, polycystic liver and kidney disease, and liver cirrhosis along with hepatorenal syndrome (HRS). The most common encountered complications following CLKTx were infection, bleeding, biliary complications, retransplantation of the liver, acute hepatic artery thrombosis, and retransplantation of the kidney. From the available data regarding the need for post-operative dialysis (n = 673), a total of 175 recipients (26%) required hemodialysis. During the follow-up period, 154 episodes of liver rejection (4.3%) and 113 episodes of kidney rejection (3.2%) occurred. The cumulative 1, 2, 3, and 5 yr survival of both organs were 78.2%, 74.4%, 62.4%, and 60.9%, respectively. Additionally, the cumulative 1, 2, 3, and 5 yr patient survival were 84.9%, 52.8%, 45.4%, and 42.6%, respectively. The total number of reported deaths was 181 of 2808 cases (6.4%), from them the cause of death in 99 (55%) cases was sepsis. It can be concluded that there is still no definitive evidence of better graft and patient survival in CLKTx recipients when compared with LTx alone because of the complexity of the exact definition of irreversible kidney function in LTx candidates. Additionally, CLKTx is better to be performed earlier than isolated LTx and KTx leading to the avoidance of deterioration of clinical status, high rate of graft loss, and mortality. Shorter graft ischemia time and more effective immunosuppressive regimens can reduce the incidence of graft malfunctioning in CLKTx patients. Providing a model to reliably determine the need for CLKTx seems necessary. Such a model can be shaped based upon new and precise markers of renal function, and modification of MELD system.

Increased expression of ALCAM/CD166 in pancreatic cancer is an independent prognostic marker for poor survival and early tumour relapse.

BACKGROUND: ALCAM (activated leucocyte cell adhesion molecule, synonym CD166) is a cell adhesion molecule, which belongs to the Ig superfamily. Disruption of the ALCAM-mediated adhesiveness by proteolytic sheddases such as ADAM17 has been suggested to have a relevant impact on tumour invasion. Although the expression of ALCAM is a valuable prognostic and predictive marker in several types of epithelial tumours, its role as a prognostic marker in pancreatic cancer has not yet been reported. METHODS: In this study, paraffin-embedded samples of 97 patients with pancreatic cancer undergoing potentially curative resection were immunostained against ALCAM, ADAM17 and CK19. Expression of ALCAM and ADAM17 was semiquantitatively evaluated and correlated to clinical and histopathological parameters. RESULTS: We could show that in normal pancreatic tissue, ALCAM is predominantly expressed at the cellular membrane, whereas in pancreatic tumour cells, it is mainly localised in the cytoplasm. In addition, univariate and multivariate analyses show that increased expression of ALCAM is an adverse prognostic factor for recurrence-free and overall survival. Overexpression of ADAM17 in pancreatic cancer, however, failed to be a significant prognostic marker and was not coexpressed with ALCAM. CONCLUSIONS: Our findings support the hypothesis that the disruption of ALCAM-mediated adhesiveness is a relevant step in pancreatic cancer progression. Moreover, ALCAM overexpression is a relevant independent prognostic marker for poor survival and early tumour relapse in pancreatic cancer.

Meta-analysis of standard, restrictive and supplemental fluid administration in colorectal surgery.

BACKGROUND: Optimal fluid therapy for colorectal surgery remains uncertain. METHODS: A simple model was applied to define standard, restrictive and supplemental fluid administration. These definitions enabled pooling of data from different trials. Randomized controlled trials on fluid amount (standard versus restrictive or supplemental amount) and on guidance for fluid administration (goal-directed fluid therapy by oesophageal Doppler-derived variables versus conventional haemodynamic variables) in patients with colorectal resection were eligible for inclusion. The primary outcome measure was postoperative morbidity. Secondary endpoints were mortality, cardiopulmonary morbidity, wound infection, anastomotic failure, recovery of bowel function and hospital stay. A random-effects model was applied. RESULTS: Nine randomized controlled trials were included. Restrictive fluid amount (odds ratio (OR) 0.41 (95 per cent confidence interval (c.i.) 0.22 to 0.77); P = 0.005) and goal-directed fluid therapy by means of oesophageal Doppler-derived variables (OR 0.43 (95 per cent c.i. 0.26 to 0.71); P = 0.001) significantly reduced overall morbidity. There were no significant differences in the secondary endpoints analysed. CONCLUSION: Using standardized definitions, this meta-analysis suggests that restrictive rather than standard fluid amount according to current textbook opinion, and goal-directed fluid therapy rather than fluid therapy guided by conventional haemodynamic variables, reduce morbidity after colorectal resection.

Systematic review and meta-analysis of the effect of portal triad clamping on outcome after hepatic resection.

BACKGROUND: The effect of portal triad clamping (PTC) on outcome after hepatic resection is uncertain. METHODS: A systematic literature search was conducted to detect randomized controlled trials (RCTs) assessing the effectiveness and safety of PTC alone and of PTC with ischaemic preconditioning (IPC) of the liver. Studies on clamping of the inferior vena cava or hepatic veins were excluded. Endpoints included postoperative overall morbidity and mortality, cardiopulmonary and hepatic morbidity, blood loss, transfusion rates and alanine aminotransferase (ALT) levels. Meta-analyses were performed using a random-effects model. RESULTS: Eight RCTs published between 1997 and 2006 containing a total of 558 patients were eligible for final analysis. The design of the identified studies varied considerably. Analyses of endpoints revealed no difference between intermittent PTC and no PTC. Meta-analyses of PTC with and without previous IPC revealed no differences, but postoperative ALT levels were significantly lower with IPC. CONCLUSION: On currently available evidence, the routine use of PTC does not offer any benefit in perioperative outcome after liver resection. It cannot be recommended as a standard procedure.

Influence of two different resection techniques (conventional liver resection versus anterior approach) of liver metastases from colorectal cancer on hematogenous tumor cell dissemination - prospective randomized multicenter trial.

BACKGROUND: Surgical hepatic resection remains the treatment of choice for patients with liver metastases from colorectal cancer despite the use of alternative therapeutic strategies. Although this procedure provides long-term survival in a significant number of patients, 50-75% of the patients develop intra- and/or extrahepatic recurrence. One possible reason for tumor recurrence may be intraoperative hematogenous tumor cell dissemination due to mechanical manipulation of the tumor during hepatic resection. Surgical technique may have an influence on hematogenous tumor cell spread. We hypothesize that hematogenous tumor cell dissemination may be reduced by using the anterior approach technique compared to conventional liver resection. METHODS/DESIGN: This is a multi-centre prospective randomized controlled, superiority trial to compare two liver resection techniques of liver metastases from colorectal cancer. 150 patients will be included and randomized intraoperatively after surgical exploration just prior to resection. The primary objective is to compare the anterior approach with the conventional liver resection technique with regard to intraoperative haematogenous tumor cell dissemination. As secondary objectives we examine five year survival rates (OS and DFS), blood loss, duration of operation, requirement of blood transfusions, morbidity rate, prognostic relevance of tumor cell detection in blood and bone marrow and the comparison of tumor cell detection by different detection methods. CONCLUSION: This trial will answer the question whether there is an advantage for the anterior approach technique compared to the conventional resection group with regard to tumor cell dissemination. It will also add further information about prognostic differences, safety, advantages and disadvantages of each technique. TRIAL REGISTRATION: Current controlled trials - ISRCTN45066244.