Genetic variation in TERT modifies the risk of hepatocellular carcinoma in alcohol-related cirrhosis: results from a genome-wide case-control study.

OBJECTIVE: Hepatocellular carcinoma (HCC) often develops in patients with alcohol-related cirrhosis at an annual risk of up to 2.5%. Some host genetic risk factors have been identified but do not account for the majority of the variance in occurrence. This study aimed to identify novel susceptibility loci for the development of HCC in people with alcohol related cirrhosis. DESIGN: Patients with alcohol-related cirrhosis and HCC (cases: n=1214) and controls without HCC (n=1866), recruited from Germany, Austria, Switzerland, Italy and the UK, were included in a two-stage genome-wide association study using a case-control design. A validation cohort of 1520 people misusing alcohol but with no evidence of liver disease was included to control for possible association effects with alcohol misuse. Genotyping was performed using the InfiniumGlobal Screening Array (V.24v2, Illumina) and the OmniExpress Array (V.24v1-0a, Illumina). RESULTS: Associations with variants rs738409 in PNPLA3 and rs58542926 in TM6SF2 previously associated with an increased risk of HCC in patients with alcohol-related cirrhosis were confirmed at genome-wide significance. A novel locus rs2242652(A) in TERT (telomerase reverse transcriptase) was also associated with a decreased risk of HCC, in the combined meta-analysis, at genome-wide significance (p=6.41×10-9, OR=0.61 (95% CI 0.52 to 0.70). This protective association remained significant after correction for sex, age, body mass index and type 2 diabetes (p=7.94×10-5, OR=0.63 (95% CI 0.50 to 0.79). Carriage of rs2242652(A) in TERT was associated with an increased leucocyte telomere length (p=2.12×10-44). CONCLUSION: This study identifies rs2242652 in TERT as a novel protective factor for HCC in patients with alcohol-related cirrhosis.

Caffeine for intestinal transit after laparoscopic colectomy: randomized clinical trial (CaCo trial).

BACKGROUND: Coffee has been suggested to help postoperative gastrointestinal motility but the mechanism is not known. This trial assessed whether caffeine shortened time to bowel activity after laparoscopic colectomy. METHODS: This was a single-centre, randomized, double-blinded, placebo-controlled superiority trial (October 2015 to August 2020). Patients aged at least 18 years undergoing elective laparoscopic colectomy were assigned randomly to receive 100 mg or 200 mg caffeine, or a placebo (250 mg corn starch) three times a day orally. The primary endpoint was the time to first bowel movement. Secondary endpoints included colonic transit time, time to tolerance of solid food, duration of hospital stay, and perioperative morbidity. RESULTS: Sixty patients were assigned randomly to either the 200-mg caffeine group (20 patients), the 100-mg caffeine group (20) or the placebo group (20). In the intention-to-treat analysis, the mean(s.d.) time to first bowel movement was 67.9(19.2) h in the 200-mg caffeine group, 68.2(32.2) h in the 100-mg caffeine group, and 67.3(22.7) h in the placebo group (P = 0.887). The per-protocol analysis and measurement of colonic transit time confirmed no measurable difference with caffeine. CONCLUSION: Caffeine was not associated with reduced time to first bowel movement. REGISTRATION NUMBER: NCT02510911 (http://www.clinicaltrials.gov).

4/5 Gastrectomy in Patients Undergoing Pancreaticoduodenectomy Reduces Delayed Gastric Emptying.

BACKGROUND: Delayed gastric emptying (DGE) is a frequent complication after pancreaticoduodenectomy (PD), impairing oral food intake and reducing the quality of life. The aim of this study was to investigate the effect of 4/5 gastrectomy on DGE after PD. MATERIALS AND METHODS: Patients undergoing pylorus-preserving PD (ppPD) were compared with PD with 4/5 subtotal gastrectomy, including resection of the gastric fundus (SGPD). The primary endpoint was DGE, according to the International Study Group of Pancreatic Surgery definition. Secondary outcomes included time to solid food intake, time to first flatus, postoperative morbidity, and body weight change 6- and 12-wk after surgery. RESULTS: Sixty patients underwent either ppPD (n = 32) or SGPD (n = 28). Patient characteristics were well balanced between the groups. DGE occurred in 47% after ppPD and 18% after SGPD (P = 0.027). Compared with ppPD, time to solid food intake and time to first flatus were significantly shorter after SGPD (8 d [interquartile range 5-12] versus 5 d [4-6]; P = 0.003 and 5 d [4-7] versus 3 d [2-5]; P = 0.001, respectively). Major postoperative morbidity and hospital stay was similar between the groups. Weight loss at 6 wk was less pronounced after ppPD (-4.8% [-6.3 to -2.7] versus -7.5% [-8.9 to -5.9]; P = 0.013), however, comparable after 3 and 6 mo (ppPD -7.6% [-8.5 to -4.8] versus SGPD -8.4% [-17.3 to -5.2]; P = 0.334 and ppPD -6.0% [-14.5 to 6.0] versus SGPD -9.5% [-11.8 to -7.0], P = 0.414, respectively). CONCLUSIONS: Compared with pylorus preservation, 4/5 gastrectomy significantly reduced the frequency of DGE and led to a faster gastrointestinal passage after PD. However, the benefits of a reduced DGE rate and a faster gastrointestinal passage should be carefully balanced against an increased weight loss after 4/5 gastrectomy in the early postoperative phase.

Role of lymphadenectomy in resectable pancreatic cancer.

BACKGROUND: Pancreatic cancer (PC) remains one of the most devastating malignant diseases, predicted to become the second leading cause of cancer-related death by 2030. Despite advances in surgical techniques and in systemic therapy, the 5-year relative survival remains a grim 9% for all stages combined. The extent of lymphadenectomy has been discussed intensively for decades, given that even in early stages of PC, lymph node (LN) metastasis can be detected in approximately 80%. PURPOSE: The primary objective of this review was to provide an overview of the current literature evaluating the role of lymphadenectomy in resected PC. For this, we evaluated randomized controlled studies (RCTs) assessing the impact of extent of lymphadenectomy on OS and studies evaluating the prognostic impact of anatomical site of LN metastasis and the impact of the number of resected LNs on OS. CONCLUSIONS: Lymphadenectomy plays an essential part in the multimodal treatment algorithm of PC and is an additional therapeutic tool to increase the chance for surgical radicality and to ensure correct staging for optimal oncological therapy. Based on the literature from the last decades, standard lymphadenectomy with resection of at least ≥ 15 LNs is associated with an acceptable postoperative complication risk and should be recommended to obtain local radicality and accurate staging of the disease. Although radical surgery including appropriate lymphadenectomy of regional LNs remains the only chance for long-term tumor control, future studies specifically assessing the impact of neoadjuvant therapy on extraregional LNs are warranted.

Role of lymphadenectomy, adjuvant chemotherapy, and treatment at high-volume centers in patients with resected pancreatic cancer-a distinct view on lymph node yield.

PURPOSE: While the importance of lymphadenectomy is well-established for patients with resectable pancreatic cancer, its direct impact on survival in relation to other predictive factors is still ill-defined. METHODS: The National Cancer Data Base 2006-2015 was queried for patients with resected pancreatic adenocarcinoma (stage IA-IIB). Patients were dichotomized into the following two groups, those with 1-14 resected lymph nodes and those with ≥ 15. Optimal number of resected lymph nodes and the effect of lymphadenectomy on survival were assessed using various statistical modeling techniques. Mediation analysis was performed to differentiate the direct and indirect effect of lymph node resection on survival. RESULTS: A total of 21,912 patients were included; median age was 66 years (IQR 59-73), 48.9% were female. Median number of resected lymph nodes was 15 (IQR 10-22), 10,163 (46.4%) had 1-14 and 11,749 (53.6%) had ≥ 15 lymph nodes retrieved. Lymph node positivity increased by 4.1% per lymph node up to eight examined lymph nodes, and by 0.6% per lymph node above eight. Five-year overall survival was 17.9%. Overall survival was better in the ≥ 15 lymph node group (adjusted HR 0.91, CI 0.88-0.95, p < 0.001). On a continuous scale, survival improved with increasing LNs collected. Patients who underwent adjuvant chemotherapy and were treated at high-volume centers had improved overall survival compared with their counterparts (adjusted HR 0.59, CI 0.57-0.62, p < 0.001; adjusted HR 0.86, CI 0.83-0.89, p < 0.001, respectively). Mediation analysis revealed that lymphadenectomy had only 18% direct effect on improved overall survival, while 82% of its effect were mediated by other factors like treatment at high-volume hospitals and adjuvant chemotherapy. DISCUSSION: While higher number of resected lymph nodes increases lymph node positivity and is associated with better overall survival, most of the observed survival benefit is mediated by chemotherapy and treatment at high-volume centers.

Posterior enucleation of the pancreatic head: an alternative route of access for parenchyma-sparing pancreatic resection.

BACKGROUND: Enucleation has become an alternative treatment in benign or low-malignant cystic tumors, including intraductal papillary mucinous neoplasms (IPMN). For enucleation to be a safe alternative to the standard procedures, there must be good access to the resection area. In this report, we present such a route for dorsally situated IPMNs. METHODS: The head of the pancreas was exposed by an extended Kocher maneuver to the left lateral edge of the aorta. Stay sutures were placed along the second part of the duodenum to allow maximal rotation of the pancreatic head to the left, which exposed the posterior aspect of the pancreatic head. The cystic lesion was then enucleated followed by a protective pancreaticojejunostomy on the resection cavity. RESULTS: Two consecutive patients with IPMNs of the dorsal pancreatic head successfully underwent dorsal enucleation. The postoperative course was uneventful in the first patient, while the course of the second patient was complicated by a clinically relevant pancreatic fistula, delayed gastric emptying, and hospital discharge on day 35. CONCLUSION: This study shows the feasibility of a dorsal approach to the pancreatic head for enucleation as well as reconstruction by means of posterior Roux-en-Y pancreaticojejunostomy. In very selected cases in specialized centers, cystic lesions in the posterior aspect of the pancreatic head will become amenable to enucleation with preservation of pancreatic functionality. However, more research is needed to clarify postoperative outcomes of this approach.

Perioperative blood transfusions do not impact overall and disease-free survival after curative rectal cancer resection: a propensity score analysis.

OBJECTIVE: To assess the putative impact of perioperative blood transfusions on overall and disease-free survival in patients undergoing curative resection of stage I-III rectal cancer by applying propensity-scoring methods. BACKGROUND: Whether perioperative blood transfusions negatively impact survival remains a matter of great debate. METHODS: In a single-center study, 401 patients undergoing open curative resection of stage I-III rectal cancer between 1996 and 2008 were assessed. The median follow-up was 34.2 months. Patients who did and did not receive perioperative blood transfusions were compared using Cox regression and propensity score analyses. RESULTS: Overall, 217 patients (54.1%) received blood transfusions. Patients' characteristics were highly biased concerning transfusions (propensity score 0.77±0.23 vs. 0.28±0.25; P<0.001). In unadjusted analysis, blood transfusions were associated with a 119% increased risk of mortality [hazard ratio (HR): 2.19, 95% confidence interval (CI): 1.34-3.57, P=0.001]. In propensity score-adjusted Cox regression (HR: 1.02, 95% CI: 0.65-1.58, P=0.970), blood transfusions did not increase the risk of overall survival. Similarly, in propensity score-adjusted Cox regression (HR: 0.86, 95% CI: 0.60-1.23, P=0.672), blood transfusions were not associated with an increased risk of recurrence. CONCLUSIONS: This is the first propensity score-based analysis providing compelling evidence that worse oncological outcomes after curative rectal cancer resection in patients receiving perioperative blood transfusions are caused by the clinical circumstances requiring transfusions, not due to the blood transfusions themselves. Therefore, concerns about overall and disease-free survival should be no issue in the decision-making regarding perioperative blood transfusions in patients undergoing curative rectal cancer resection.

Allogeneic blood transfusion does not affect outcome after curative resection for advanced cholangiocarcinoma.

PURPOSE: To assess the impact of perioperative blood transfusion on overall and disease-free survival in patients undergoing curative resection for cholangiocarcinoma. METHODS: In a single-center study, 128 patients undergoing curative resection for cholangiocarcinoma between 2001 and 2010 were assessed. The median follow-up period was 19 months. Transfused and nontransfused patients were compared by Cox regression and propensity score analyses. RESULTS: Overall, 38 patients (29.7 %) received blood transfusions. The patient characteristics were highly biased with respect to receiving transfusions (propensity score 0.69 ± 0.22 vs. 0.11 ± 0.16, p < 0.001). In the unadjusted analysis, blood transfusion was associated with a 105 % increased risk of mortality [hazard ratio (HR) 2.05, 95 % CI 1.19-3.51, p = 0.010]. In the multivariate (HR 1.14, 95 % CI 0.52-2.48, p = 0.745) and the propensity score-adjusted Cox regression (HR 1.02, 95 % CI 0.39-2.62, p = 0.974), blood transfusion had no influence on overall survival. Similarly, in the propensity score-adjusted Cox regression (HR 0.62, 95 % CI 0.24-1.58, p = 0.295), no relevant effect of blood transfusion on disease-free survival was observed. CONCLUSIONS: To our knowledge, this is the first propensity score-based analysis providing compelling evidence that the worse oncological outcome after curative resection for advanced cholangiocarcinoma in patients receiving perioperative blood transfusions is caused by the clinical circumstances requiring the transfusions, not by the blood transfusions themselves.

Use of human fibrin glue (Tisseel) versus staples for mesh fixation in laparoscopic transabdominal preperitoneal hernioplasty (TISTA): a randomized controlled trial (NCT01641718).

BACKGROUND: Inguinal hernia repair is one of the most common surgical procedures worldwide. This procedure is increasingly performed with endoscopic techniques (laparoscopy). Many surgeons prefer to cover the hernia gap with a mesh to prevent recurrence. The mesh must be fixed tightly, but without tension. During laparoscopic surgery, the mesh is generally fixed with staples or tissue glue. However, staples often cause pain at the staple sites, and they can cause scarring of the abdominal wall, which can lead to chronic pain. We designed a trial that aims to determine whether mesh fixation with glue might cause less postoperative pain than fixation with staples during a transabdominal preperitoneal patch plastic repair. METHODS/DESIGN: The TISTA trial is a prospective, randomized, controlled, single-center trial with a two-by-two parallel design. All patients and outcome-assessors will be blinded to treatment allocations. For eligibility, patients must be male, ≥18 years old, and scheduled for laparoscopic repair of a primary inguinal hernia. One group comprises patients with a unilateral inguinal hernia that will be randomized to receive mesh fixation with either tissue glue or staples. The second group comprises patients with bilateral inguinal hernias. They will be randomized to receive mesh fixation with tissue glue either on the right or the left side and with staples on the other side. The primary endpoint will be pain under physical stress, measured at 24 h after surgery. Pain will be rated by the patient based on a numeric rating scale from 0 to 10, where 10 equals the worst pain imaginable. A total of 82 patients will be recruited (58 patients with unilateral inguinal hernias and 24 patients with bilateral hernias). This number is estimated to provide 90% power for detecting a pain reduction of one point on a numeric rating scale, with a standard deviation of one. DISCUSSION: Patients with bilateral hernias will receive two meshes, one fixed with glue, and the other fixed with staples. This design will eliminate the inter-individual bias inherent in comparing pain measurements between two groups of patients. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01641718.

Blood transfusion does not adversely affect survival after elective colon cancer resection: a propensity score analysis.

PURPOSE: The aim of this study was to assess the putative impact of perioperative blood transfusions on overall survival in patients undergoing curative resection for stage III colon cancer by applying propensity scoring methods. METHODS: In a single-center study, a total of 309 patients who underwent open curative resection for stages I-III colon cancer from 1996-2008 were assessed. The mean follow-up period was 47 ± 38 months. Transfused and non-transfused patients were compared using both Cox regression and propensity score analyses. RESULTS: Overall, 148 patients (47.9 %) received blood transfusions. The patient characteristics were highly biased toward transfusions (propensity score 0.68 ± 0.22 vs. 0.30 ± 0.22, p <0.001). In the unadjusted analysis, blood transfusions were associated with a 90 % increased risk of overall mortality (hazard ratio 1.90, 95 % CI: 1.19-3.04, p = 0.001). The 5-year survival for patients receiving blood transfusions was 64.5 % (95 % CI: 56.0-74.3 %) compared with 80.1 % (95 % CI: 72.8-88.2 %) in those not receiving blood transfusions. In the propensity score-adjusted Cox regression analysis (hazard ratio: 0.85, 95 % CI = 0.53-1.37, p = 0.501), blood transfusions did not increase the risk of overall mortality. After risk adjustment, the 5-year survival rate for patients receiving blood transfusions was 66.6 % (95 % CI: 57.4-77.3 %) compared with 61.8 % (95 % CI: 51.9-73.7 %) for those who did not. CONCLUSION: This study is the first propensity score-based analysis that provides evidence that poor oncological outcomes after curative colon cancer resection in patients receiving perioperative blood transfusions are due to the clinical circumstances that require the transfusions and are not due to the blood transfusions.

IPMN: surgical treatment.

PURPOSE: Cystic pancreatic tumors are being detected more frequently, and particularly, intraductal papillary mucinous neoplasia (IPMN) has recently attracted increased attention. The detection rate of IPMN has increased over the last decade; however, management of this neoplasm remains controversial. METHODS: Based on a review of the relevant literature and the international guidelines, we discuss the diagnostic evaluation of IPMN, its treatment, and prognosis. RESULTS: While IPMN represents only a distinct minority of all pancreatic cancers, they appear to be a relatively frequent neoplastic form of pancreatic cystic neoplasm. It may not be possible to differentiate main duct disease from branch duct disease (MD-IPMN vs. BD-IPMN) prior to surgery. This distinction has not only an impact on treatment but also on prognosis, as MD-IPMN is more often malignant. IPMN has updated consensus guideline indications for conservative and surgical resection. CONCLUSIONS: Since patients with IPMN of the pancreas are at risk of developing recurrent IPMN and pancreatic ductal adenocarcinoma in the remnant pancreas and extrapancreatic malignancies, early recognition, treatment, and systemic surveillance are of great importance. No conclusions can be drawn from the available evidence with respect to the efficacy of surveillance and follow-up treatment programs. A better understanding of the natural course of IPMN and the biology of pancreatic cancer is mandatory to enable further diagnostic and treatment improvements.

Study protocol for a randomized, double-blind, placebo-controlled trial of a single preoperative steroid dose to prevent nausea and vomiting after thyroidectomy: the tPONV study.

BACKGROUND: Postoperative nausea and vomiting after general anesthesia is not only an unpleasant problem affecting 20-30% of surgical patients but may also lead to severe postoperative complications. There is a particularly high incidence of postoperative nausea and vomiting following thyroidectomy. Dexamethasone has been described as highly effective against chemotherapy-induced nausea and vomiting and has been proposed as a first-line method of postoperative nausea and vomiting prophylaxis. Despite this possible beneficial effect, the prophylactic administration of dexamethasone before surgery to prevent or ameliorate postoperative nausea and vomiting has not been established. A bilateral superficial cervical plexus block during thyroid surgery under general anesthesia significantly reduces pain. Of even greater clinical importance, this block prevents the need for postoperative opioids. Therefore, patients undergoing thyroidectomy and a bilateral superficial cervical plexus block are an ideal group to investigate the efficacy of dexamethasone for postoperative nausea and vomiting. These patients have a high incidence of postoperative nausea and vomiting and do not require opioids. They have no abdominal surgery, which can cause nausea and vomiting via a paralytic ileus. Combined with the highly standardized anesthesia protocol in use at our institution, this setting allows all known biases to be controlled. METHODS/DESIGN: We will perform a parallel two-arm, randomized (1:1), double-blind, placebo-controlled, single-center trial. Adults (≥18 years) scheduled for primary partial or total thyroidectomy because of a benign disease will be eligible for inclusion. The participants will be randomized to receive a single, intravenous preoperative dose of either 8 mg of dexamethasone in 2 ml saline (treatment group) or saline alone (placebo group). All the patients will receive a bilateral superficial cervical plexus block and standardized anesthesia. The primary outcome will be the incidence of postoperative nausea and vomiting. A total of 152 patients will be recruited, providing 80% power to detect a 50% reduction in the incidence of postoperative nausea and vomiting. Any patients who require opioid treatment will be excluded from the per-protocol analysis. DISCUSSION: In the present protocol, we reduced bias to the greatest extent possible. Thus, we expect to definitively clarify the efficacy of dexamethasone for postoperative nausea and vomiting prophylaxis. TRIAL REGISTRATION: http://www.clinicaltrials.gov: NCT01189292.

Safe and early discharge after colorectal surgery due to C-reactive protein: a diagnostic meta-analysis of 1832 patients.

OBJECTIVE: To assess the predictive value of C-reactive protein (CRP) level for postoperative infectious complications after colorectal surgery. BACKGROUND: Postoperative infectious complications after colorectal surgery are frequent and associated with relevant short- and long-term sequelae. Therefore, the identification of a diagnostic tool for early recognition of postoperative infectious complications is of cardinal importance. METHODS: A meta-analysis was performed for diagnostic studies evaluating CRP as a predictor for postoperative infectious complications on days 1 to 5 after colorectal surgery. RESULTS: Six studies including a total of 1832 patients were identified. The best performance of CRP to predict postoperative infectious complications was on postoperative day 4, on which the mean CRP cutoff value was 135 mg/L (SD: 10 mg/L), the pooled sensitivity 68% (95% CI: 57%-79%), the specificity 83% (95% CI: 77%-90%) and the negative predictive value 89% (95% CI: 87%-92%). The pooled area under the receiver operating characteristic curve was 0.81 (95% CI: 0.73-0.89). CONCLUSIONS: This diagnostic meta-analysis of 1832 patients--the first in the literature--provides compelling evidence that C-reactive protein on postoperative day 4 has a high negative predictive value for infectious complications of 89%. Therefore, CRP measurement allows safe and early discharge of selected patients after colorectal surgery.

Pancreatic surgery: beyond the traditional limits.

Pancreatic cancer is one of the five leading causes of cancer death for both males and females in the western world. More than 85 % pancreatic tumors are of ductal origin but the incidence of cystic tumors such as intrapapillary mucinous tumors (IPMN) or mucinous cystic tumors (MCN) and other rare tumors is rising. Complete surgical resection of the tumor is the mainstay of any curative therapeutic approach, however, up to 40 % of patients with potentially resectable pancreatic cancer are not offered surgery. This is despite 5-year survival rates of up to 40 % or even higher in selected patients depending on tumor stage and histology. Standard procedures for pancreatic tumors include the Kausch-Whipple- or pylorus-preserving Whipple procedure, and the left lateral pancreatic resection (often with splenectomy), and usually include regional lymphadenectomy. More radical or extended pancreatic operations are becoming increasingly utilised however and we examine the data available for their role. These operations include major venous and arterial resection, multivisceral resections and surgery for metastatic disease, or palliative pancreatic resection. Portal vein resection for local infiltration with or without replacement graft is now well established and does not deleteriously affect perioperative morbidity or mortality. Arterial resection, however, though often technically feasible, has questionable oncologic impact, is not without risk and is usually reserved for isolated cases. The value of extended lymphadenectomy is frequently debated; the recent level I evidence demonstrates no advantage. Multivisceral resections, i.e. tumors, often in the tail of the pancreas, with invasion of the colon or stomach or other surrounding tissues, while associated with an increased morbidity and a longer hospital stay, do however show comparable mortality-and survival rates to those without such infiltration and therefore should be performed if technically feasible. Routine resection for metastatic disease however does not seem to show any advantage over palliative treatment but may be an option in selected patients with easily removable metastases. In conclusion pancreatic surgery beyond the traditional limits is established in tumors infiltration the venous system and may be a considered approach in selected patients with locally infiltrating pancreatic cancer or metastasis.

Diagnostic study and meta-analysis of C-reactive protein as a predictor of postoperative inflammatory complications after gastroesophageal cancer surgery.

PURPOSE: This study assessed the diagnostic accuracy of C-reactive protein (CRP) after gastroesophageal cancer resection for postoperative inflammatory complications (PIC). METHODS: The clinical data and CRP values of patients operated on for gastroesophageal cancer surgery between 1997 and 2009 were retrospectively analyzed. The results of this study were compared with published data using a meta-analytic approach for diagnostic outcomes. RESULTS: Of 210 patients included in the study, 59 developed PIC (28.1 %; 95 % CI: 22.5-34.5 %). On the postoperative day (POD) 4 and 7, CRP had the best diagnostic accuracy for PIC (AUC 0.77; 95 % CI, 0.64-0.91, AUC 0.81; 95 % CI, 0.71-0.91). Using a cut-off value of 141 mg/L (95 % CI, 131-278 mg/L) for CRP on POD 4, the sensitivity was 0.78 (95 % CI, 0.55-0.91), the specificity was 0.70 (95 % CI, 0.53-0.83) and the NPV was 0.89 (95 % CI, 0.77-0.95). The in-hospital mortality rate was 3.3 % (95 % CI, 1.5-6.9 %). In a diagnostic meta-analysis that included two additional studies, CRP had a significant predictive value after POD 3. CONCLUSION: There is limited evidence for the diagnostic accuracy of CRP levels for PIC after gastroesophageal cancer surgery. CRP levels on POD 4 might be useful to rule out PIC, but its diagnostic accuracy is moderate at best. For clinical routine use CRP levels are clearly not sufficient to predict PIC and have to be interpreted in the context of the whole clinical picture.

Hepatocellular carcinoma: current management and perspectives for the future.

OBJECTIVE: To review the literature on current management of hepatocellular carcinoma (HCC). BACKGROUND: Hepatocellular carcinoma represents one of the most common malignancies worldwide with a rising incidence in western countries. There have been substantial advances in the surgical and medical treatment of HCC within the past 2 decades. METHODS: A literature review was performed in the MEDLINE database to identify studies on the management of HCC. On the basis of the available evidence recommendations for practice were graded using the Oxford Centre for Evidence-based Medicine classification. RESULTS: Advances in surgical technique and perioperative care have established surgical resection and orthotopic liver transplantation (OLT) as primary curative therapy for HCC in noncirrhotic and cirrhotic patients, respectively. Primary resection and salvage OLT may be indicated in cirrhotics with preserved liver function. Selection criteria for OLT remain debated, as slight expansion of the Milan criteria may not worsen prognosis but is limited by organ shortage and prolonged waiting time with less favorable outcome on intention-to-treat analyses. Strategies of neoadjuvant treatment before OLT require evaluation within prospective trials. Transarterial chemoembolization is the primary therapy in patients with inoperable HCC and compensated liver function. Although systemic chemotherapy is not effective in patients with advanced HCC, there is recent evidence that these patients benefit from new molecular targeted therapies. If these agents are also effective in the neoadjuvant and adjuvant setting is currently being investigated. Furthermore, selective intra-arterial radiation therapy represents a promising new approach for treatment of unresectable HCC. CONCLUSIONS: Recent developments in the surgical and medical therapy have significantly improved outcome of patients with operable and advanced HCC. A multidisciplinary approach seems essential to further improve patients' prognosis.

Liver tissue sparing resection using a novel planning tool.

PURPOSE: Accurate preoperative prediction of liver function, volume, and vessel anatomy is essential in preventing postoperative liver failure, optimizing safety, and ensuring optimal outcome in patients undergoing hepatic surgery. We propose that preoperative resection planning provides useful anatomical and volumetric data, allowing for sparing of liver tissue in surgical resections. The purpose of the present study was to evaluate the use of a novel resection planning tool. METHODS: Thirteen patients undergoing hemihepatectomy were included. Preoperative resection planning was performed using the commercially available software Mint Liver. During resection planning, virtual resections were calculated based on Couinaud classification, Cantlie's line (standard), and individually by the operating surgeon (individual). Intraoperatively, volume and weight of the resected specimen were measured. A 14-day follow-up was conducted, and laboratory parameters were collected. Statistical analysis was performed, comparing virtual resection volumes (i.e., standard vs. individual) and secondarily virtual vs. actual resection volume. RESULTS: We found a significant difference (p = 0.001) in the comparison of standard vs. individual in all 13 cases, with an average 92.8 mL smaller resected volume, sparing 11.3% of liver parenchyma with virtual resection. No patients suffered from acute liver failure. Perioperative mortality was 0%. CONCLUSION: Mint Liver is capable of acquiring exact anatomical and volumetric knowledge prior to hepatic resections. Liver parenchyma can be spared by preoperative assessment of the resection plan. We propose that this tool could be an important addition to preoperative patient evaluation, especially in complex liver surgery and living donor liver transplantation where precise volumetry is the decisive factor.

Exact CT-based liver volume calculation including nonmetabolic liver tissue in three-dimensional liver reconstruction.

Exact preoperative determination of the liver volume is of great importance prior to hepatobiliary surgery, especially in living donated liver transplantation (LDLT) and extended hepatic resections. Modern surgery-planning systems estimate these volumes from segmented image data. In an experimental porcine study, our aim was (1) to analyze and compare three volume measurement algorithms to predict total liver volume, and (2) to determine vessel tree volumes equivalent to nonmetabolic liver tissue. Twelve porcine livers were examined using a standardized three-phase computed tomography (CT) scan and liver volume was calculated computer-assisted with the three different algorithms. After hepatectomy, livers were weighed and their vascular system plasticized followed by CT scan, CT reconstruction and re-evaluation of total liver and vessel volumes with the three different algorithms. Blood volume determined by the plasticized model was at least 1.89 times higher than calculated by multislice CT scans (9.7% versus 21.36%, P=0.028). Analysis of 3D-CT-volumetry showed good correlation between the actual and the calculated liver volume in all tested algorithms with a high significant difference in estimating the liver volume between Heymsfield versus Heidelberg (P=0.0005) and literature versus Heidelberg (P=0.0060). The Heidelberg algorithm reduced the measuring error with deviations of only 1.2%. The present results suggest a safe and highly predictable use of 3D-volumetry in liver surgery for evaluating liver volumes. With a precise algorithm, the volume of remaining liver or single segments can be evaluated exactly and potential operative risks can therefore be better calculated. To our knowledge, this study implies for the first time a blood pool, which corresponds to nonmetabolic liver tissue, of more than 20% of the whole liver volume.

A single-center experience of 500 liver transplants using the modified piggyback technique by Belghiti.

Over the past 4 decades, the surgical techniques of liver transplantation (LTx) have permanently evolved and been modified. Among these, the modified piggyback (MPB) technique by Belghiti offers specific advantages. The objective of this study was to present our single-center experience with the MPB technique in 500 cases. Recipients' perioperative data were prospectively collected and evaluated. Postoperative and specific complications, stay in the intensive and intermediate care unit, and the mortality rate with cause of death were analyzed. Most recipients were classified as Child C (49.1%). For the patients who underwent LTx for the first time, alcoholic (23.9%) and viral (22.2%) cirrhosis and hepatocellular carcinoma (15.1%) were the prevalent indications. The overall median warm ischemia time, anastomosis duration, and operative time were 45, 108, and 320 minutes, respectively. The median intraoperative blood loss was 1500 mL. A venovenous bypass was never needed to maintain hemodynamic stability. Only in a few cases was temporary inferior vena cava clamping necessary. Most prominent surgical complications were hemorrhage, hematoma, and wound dehiscence. Renal failure occurred in 6.2% of patients. The overall median stay in the intensive and intermediate care unit was 14 days. The mortality rates within 30 and 90 days were 6.3% and 13.3%, respectively. No technique-related death occurred. The MPB technique by Belghiti is a feasible and simple LTx technique. The caval flow is preserved during the anhepatic phase, and this minimizes the need for venovenous bypass or portocaval shunt. This technique requires only 1 caval anastomosis, which is easy to perform with a short anhepatic phase. To minimize the risk of outflow obstruction, attention should be paid by doing a wide cavocavostomy cranially to the donor inferior vena cava in a door-lock manner. This technique can be applied in almost all patients undergoing LTx for the first time and liver retransplantation as well.

Validation of prognostic scoring systems for patients undergoing resection of colorectal cancer liver metastases.

BACKGROUND: Several prognostic scoring systems have been established for patients undergoing resection of colorectal cancer (CRC) liver metastases; however, comparative analyses of their prognostic relevance is still lacking in the literature. The aim of the present study was to assess the predictive value of five published scoring systems in an independent patient cohort for the purpose of external validation. METHODS: A total of 281 patients underwent liver resection for CRC liver metastases at our institution between January 2002 and January 2008. The predictive value of the Nordlinger score, Memorial Sloan-Kettering Cancer Center (MSKCC) score, Iwatsuki score, Basingstoke index, and Mayo scoring system was assessed in this patient set. Furthermore, clinical and pathologic parameters included in the assessed scoring systems were analyzed by means of univariate and multivariate analyses. RESULTS: The disease-specific survival at 1, 3, and 5 years was 94.6%, 61.8%, and 33.7%, respectively. Of the assessed scoring systems, only the MSKCC score (P = .006) and the Iwatsuki score (P = .01) provided a statistically significant stratification of patients with regard to survival. The predictive value was particularly evident for patients grouped within the high-risk categories. None of these patients was alive at 3 years after surgery. The 3-year survival rates for high-risk patients in the remaining three scoring systems was > 50%. CONCLUSIONS: In our patient cohort, survival was only predicted by MSKCC and Iwatsuki scores. These findings highlight the importance of validating scoring systems in independent patient groups.