Jan H.M.B. Stoot

Malignant transformation of hepatocellular adenomas into hepatocellular carcinomas: a systematic review including more than 1600 adenoma cases

BACKGROUND Malignant transformation of hepatocellular adenomas (HCAs) into hepatocellular carcinomas (HCCs) has been reported repeatedly and is considered to be one of the main reasons for surgical treatment. However, its actual risk is currently unknown. OBJECTIVE To provide an estimation of the frequency of malignant transformation of HCAs and to discuss its clinical implications. METHODS A systematic literature search was conducted using the following databases: The Cochrane Hepatobiliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, MEDLINE and EMBASE. RESULTS One hundred and fifty-seven relevant series and 17 case reports (a total of 1635 HCAs) were retrieved, reporting an overall frequency of malignant transformation of 4.2%. Only three cases (4.4%) of malignant alteration were reported in a tumour smaller than 5 cm in diameter. DISCUSSION Malignant transformation of HCAs into HCCs remains a rare phenomenon with a reported frequency of 4.2%. A better selection of exactly those patients presenting with an HCA with an amplified risk of malignant degeneration is advocated in order to reduce the number of liver resections and thus reducing the operative risk for these predominantly young patients. The Bordeaux adenoma tumour markers are a promising method of identifying these high-risk adenomas.

Functional compromise reflected by sarcopenia, frailty, and nutritional depletion predicts adverse postoperative outcome after colorectal cancer surgery

OBJECTIVE To determine the association of sarcopenia with postoperative morbidity and mortality after colorectal surgery. BACKGROUND Functional compromise in elderly colorectal surgical patients is considered as a significant factor of impaired postoperative recovery. Therefore, the predictive value of preoperative functional compromise assessment was investigated. Sarcopenia is a hallmark of functional compromise. METHODS A total of 310 consecutive patients who underwent oncologic colorectal surgery were included in a prospective digital database. Sarcopenia was assessed using the L3 muscle index utilizing Osirix on preoperative computed tomography. Groningen Frailty Indicator and Short Nutritional Assessment Questionnaire scores were used to assess frailty and nutritional compromise. Predictors for anastomotic leakage, sepsis, and mortality were analyzed by logistic regression analysis. RESULTS Age was an independent predictor of mortality [P = 0.04; odds ratio, 1.17; 95% confidence interval (CI), 1.01-1.37]. Thirty-day/in-hospital mortality rate in sarcopenic patients was 8.8% versus 0.7% in nonsarcopenic patients (P = 0.001; odds ratio, 15.5; 95% CI, 2.00-120). Sarcopenia was not predictive for anastomotic leakage or sepsis. Combination of high Short Nutritional Assessment Questionnaire score, high Groningen Frailty Indicator score, and sarcopenia strongly predicted sepsis (P = 0.001; odds ratio, 25.1; 95% CI, 5.11-123), sensitivity, 46%; specificity, 97%; positive likelihood ratio, 13 (95% CI, 4.4-38); negative likelihood ratio, 0.57 (95% CI, 0.33-0.97). CONCLUSIONS Functional compromise in colorectal cancer surgery is associated with adverse postoperative outcome. Assessment of functional compromise by means of a nutritional questionnaire (Short Nutritional Assessment Questionnaire), a frailty questionnaire (Groningen Frailty Indicator), and sarcopenia measurement (L3 muscle index) can accurately predict postoperative sepsis.

The effect of a multimodal fast-track programme on outcomes in laparoscopic liver surgery: a multicentre pilot study

OBJECTIVES This study was conducted to evaluate the added value of an enhanced recovery after surgery (ERAS) programme in laparoscopic liver resections for solid tumours. METHODS Patients undergoing laparoscopic liver resection between July 2005 and July 2008 were included. Indications for resections included presumed benign and malignant liver lesions. Primary outcome was total length of hospital stay (LOS). Secondary outcomes were functional recovery, complications, conversions, blood loss and duration of operation. RESULTS Thirteen patients were treated by laparoscopic liver resections in the ERAS programme in one centre (group 1). Their outcomes were compared with outcomes of 13 laparoscopic procedures performed either before the introduction of the ERAS programme during 2003-2005 in the same centre or during the same period in other centres using traditional care (group 2). Median total LOS was 5.0 days (range 3-10 days) in group 1 and 7.0 days (3-12 days) in group 2. This difference was not statistically significant. Functional recovery occurred 2 days earlier in group 1 (median 3.0 days [range 1-7 days] vs. median 5.0 days [range 2-8 days]; P < 0.044). There were no significant differences in complications, conversions or duration of operation. Blood loss was significantly less in the ERAS group (median 50 ml [range 50-200 ml] vs. median 250 ml [range 50-800 ml]; P < 0.002). CONCLUSIONS This exploratory, multicentre, fast-track laparoscopic liver resection study is the first such study conducted. Although small, the study suggests that a multimodal enhanced recovery programme in laparoscopic liver surgery is feasible, safe and may lead to accelerated functional recovery and reductions in LOS.

Open versus laparoscopic left lateral hepatic sectionectomy within an enhanced recovery ERAS® programme (ORANGE II – Trial): study protocol for a randomised controlled trial

BackgroundThe use of lLaparoscopic liver resection in terms of time to functional recovery, length of hospital stay (LOS), long-term abdominal wall hernias, costs and quality of life (QOL) has never been studied in a randomised controlled trial. Therefore, this is the subject of the international multicentre randomised controlled ORANGE II trial.MethodsPatients eligible for left lateral sectionectomy (LLS) of the liver will be recruited and randomised at the outpatient clinic. All randomised patients will undergo surgery in the setting of an ERAS programme. The experimental design produces two randomised arms (open and laparoscopic LLS) and a prospective registry. The prospective registry will be based on patients that cannot be randomised because of the explicit treatment preference of the patient or surgeon, or because of ineligibility (not meeting the in- and exclusion criteria) for randomisation in this trial. Therefore, all non-randomised patients undergoing LLS will be approached to participate in the prospective registry, thereby allowing acquisition of an uninterrupted prospective series of patients. The primary endpoint of the ORANGE II trial is time to functional recovery. Secondary endpoints are postoperative LOS, percentage readmission, (liver-specific) morbidity, QOL, body image and cosmetic result, hospital and societal costs over 1 year, and long-term incidence of incisional hernias. It will be assumed that in patients undergoing laparoscopic LLS, length of hospital stay can be reduced by two days. A sample size of 55 patients in each randomisation arm has been calculated to detect a 2-day reduction in LOS (90% power and α = 0.05 (two-tailed)).The ORANGE II trial is a multicenter randomised controlled trial that will provide evidence on the merits of laparoscopic surgery in patients undergoing LLS within an enhanced recovery ERAS programme.Trial registrationClinicalTrials.gov NCT00874224.

Sarcopenia is highly prevalent in patients undergoing surgery for gastric cancer but not associated with worse outcomes

Aim of this study was to assess the prevalence of sarcopenia and body composition (i.e., subcutaneous and visceral fat) in gastric cancer surgical patients and its association with adverse postoperative outcome.

Accurate prediction of anastomotic leakage after colorectal surgery using plasma markers for intestinal damage and inflammation

BACKGROUND Anastomotic leakage is a frequent and life-threatening complication after colorectal surgery. Early recognition of anastomotic leakage is critical to reduce mortality. Because early clinical and radiologic signs of anastomotic leakage are often nonspecific, there is an urgent need for accurate biomarkers. Markers of inflammation and gut damage might be suitable, as these are hallmarks of anastomotic leakage. STUDY DESIGN In 84 patients undergoing scheduled colorectal surgery with primary anastomosis, plasma samples were collected preoperatively and daily after surgery. Inflammatory markers, C-reactive protein; calprotectin; and interleukin-6, and intestinal damage markers, intestinal fatty acid binding protein; liver fatty acid binding protein; and ileal bile acid binding protein, were measured. Diagnostic accuracy of single markers or combinations of markers was analyzed by receiver operating characteristic curve analysis. RESULTS Anastomotic leakage developed in 8 patients, clinically diagnosed at median day 6. Calprotectin had best diagnostic accuracy to detect anastomotic leakage postoperatively. Highest diagnostic accuracy was obtained when C-reactive protein and calprotectin were combined at postoperative day 3, yielding sensitivity of 100%, specificity of 89%, positive likelihood ratio = 9.09 (95% CI, 4.34-16), and negative likelihood ratio = 0.00 (95% CI, 0.00-0.89) (p < 0.001). Interestingly, preoperative intestinal fatty acid binding protein levels predicted anastomotic leakage at a cutoff level of 882 pg/mL with sensitivity of 50%, specificity of 100%, positive likelihood ratio = infinite (95% CI, 4.01-infinite), and negative likelihood ratio = 0.50 (95% CI, 0.26-0.98) (p < 0.0001). CONCLUSIONS Preoperative intestinal fatty acid binding protein measurement can be used for anastomotic leakage risk assessment. In addition, the combination of C-reactive protein and calprotectin has high diagnostic accuracy. Implementation of these markers in daily practice deserves additional investigation.

Improving the outcomes in gastric cancer surgery

Gastric cancer remains a significant health problem worldwide and surgery is currently the only potentially curative treatment option. Gastric cancer surgery is generally considered to be high risk surgery and five-year survival rates are poor, therefore a continuous strive to improve outcomes for these patients is warranted. Fortunately, in the last decades several potential advances have been introduced that intervene at various stages of the treatment process. This review provides an overview of methods implemented in pre-, intra- and postoperative stage of gastric cancer surgery to improve outcome. Better preoperative risk assessment using comorbidity index (e.g., Charlson comorbidity index), assessment of nutritional status (e.g., short nutritional assessment questionnaire, nutritional risk screening - 2002) and frailty assessment (Groningen frailty indicator, Edmonton frail scale, Hopkins frailty) was introduced. Also preoperative optimization of patients using prehabilitation has future potential. Implementation of fast-track or enhanced recovery after surgery programs is showing promising results, although future studies have to determine what the exact optimal strategy is. Introduction of laparoscopic surgery has shown improvement of results as well as optimization of lymph node dissection. Hyperthermic intraperitoneal chemotherapy has not shown to be beneficial in peritoneal metastatic disease thus far. Advances in postoperative care include optimal timing of oral diet, which has been shown to reduce hospital stay. In general, hospital volume, i.e., centralization, and clinical audits might further improve the outcome in gastric cancer surgery. In conclusion, progress has been made in improving the surgical treatment of gastric cancer. However, gastric cancer treatment is high risk surgery and many areas for future research remain.

Improving the outcomes in oncological colorectal surgery

During the last several decades, colorectal cancer surgery has experienced some major perioperative improvements. Preoperative risk-assessment of nutrition, frailty, and sarcopenia followed by interventions for patient optimization or an adapted surgical strategy, contributed to improved postoperative outcomes. Enhanced recovery programs or fast-track surgery also resulted in reduced length of hospital stay and overall complications without affecting patient safety. After an initially indecisive start due to uncertainty about oncological safety, the most significant improvement in intraoperative care was the introduction of laparoscopy. Laparoscopic surgery for colon and rectal cancer is associated with better short-term outcomes, whereas long-term outcomes regarding survival and recurrence rates are comparable. Nevertheless, long-term results in rectal surgery remain to be seen. Early recognition of anastomotic leakage remains a challenge, though multiple improvements have allowed better management of this complication.

Life-threatening hemorrhage from adenomas in the liver during pregnancy.

A primi gravida at term was admitted to a peripheral hospital with sudden right upper abdominal pain and diagnosed as having pre-eclampsia. Labor was induced and she was referred to our hospital because of increasing pain and decreasing hemoglobin levels. At admission, ultrasound examination showed a possible liver hematoma and free abdominal fl uid. After delivery of a healthy girl, she remained hemodynamically instable. A contrast-enhanced CT scan revealed four lesions in the liver resembling adenomas and free peritoneal fl uid ( fi g.1 ). The patient could not be stabilized with conservative treatment. Selective embolization of the right hepatic artery was performed successfully ( fi g. 2 ). She was discharged home 2 weeks later. Hemorrhage in pregnancy from ruptured liver adenomas is rare and therefore easily misdiagnosed. Presentation may be with severe pain localized to the epigastrium or right upper quadrant of the abdomen with radiation to the back or right shoulder. These symptoms might be misinterpreted as dyspepsia or cholecystitis. Delay in diagnosing rupture of the liver will contribute to high mortality rates. It is essential to get the diagnosis at once, preferably using contrast-enhanced CT scanning. We suggest that selective arterial embolization is a valuable tool in the acute phase of hepatocellular adenoma bleeding.

A survey in the hepatopancreatobiliary community on ways to enhance patient recovery.

OBJECTIVES Both laparoscopic techniques and multimodal enhanced recovery programmes have been shown to improve recovery and reduce length of hospital stay. Interestingly, evidence-based care programmes are not widely implemented, whereas new, minimally invasive surgical procedures are often adopted with very little evidence to support their effectiveness. The present survey aimed to shed light on experiences of the adoption of both methods of optimizing recovery. METHODS An international, web-based, 18-question, electronic survey was composed in 2010. The survey was sent out to 673 hepatopancreatobiliary (HPB) centres worldwide in June 2010 to investigate international experiences with laparoscopic liver surgery, fast-track recovery programmes and surgery-related equipoise in open and laparoscopic techniques and to assess opinions on strategies for adopting laparoscopic liver surgery in HPB surgical practice. RESULTS A total of 507 centres responded (response rate: 75.3%), 161 of which finished the survey completely. All units reported performing open liver resections, 24.2% performed open living donor resections, 39.1% carried out orthotopic liver transplantations, 87.6% had experience with laparoscopic resections and 2.5% performed laparoscopic living donor resections. A median of 50 (range: 2-560) open and 9.5 (range: 1-80) laparoscopic liver resections per surgical unit were performed in 2009. Patients stayed in hospital for a median of 7 days (range: 2-15 days) after uncomplicated open liver resection and a median of 4 days (range: 1-10 days) after uncomplicated laparoscopic liver resection. Only 28.0% of centres reported having experience with fast-track programmes in liver surgery. The majority considered the instigation of a randomized controlled trial or a prospective register comparing the outcomes of open and laparoscopic techniques to be necessary. CONCLUSIONS Worldwide dissemination of laparoscopic liver resection is substantial, although laparoscopic volumes are low in the majority of HPB centres. The adoption of enhanced recovery programmes in liver surgery is limited and should be given greater attention.