Prevalence of microsatellite instable and Epstein-Barr Virus-driven gastroesophageal cancer in a large Belgian cohort.

Introduction: Patients with gastroesophageal adenocarcinoma (GEC) with microsatellite instability-high (MSI-H) or Epstein Barr Virus positivity (EBV+) might be good candidates for immunotherapy. Incidences of about 10% have been reported for both features, but are dependent on geographical region and disease stage. Aim: The aim is to study the prevalence of MSI-H and EBV+ in a Belgian single center cohort of patients with GEC. Methods: We retrospectively assessed the files of all patients with a newly diagnosed GEC between August, 1st 2018 and February, 29th 2020 at the University Hospitals Leuven, Belgium. Microsatellite instability (MSI) status was determined using immunohistochemistry (IHC) and polymerase chain reaction (PCR). EBV+ was assessed using in situ hybridization (ISH). A case report is provided to illustrate the importance of testing for MSI in GEC. Results: 247 gastroesophageal adenocarcinomas were included in this analysis. 62 (56% stage IV) of those were tested for EBV, but only 1 turned out to be EBV positive (1.6%). 116 patients (44.0% stage IV) were tested for MSI, of which 11 were MSI-H (9.5%). Half of the MSI-H tumors identified were at the gastroesophageal junction (GEJ). A patient with MSI-H metastatic GEC obtained a complete response with nivolumab, which persisted after discontinuation of treatment. Conclusion: While we confirm that about 10% of GECs are MSI-H, the incidence of EBV+ in our cohort (1.6%) is clearly lower than expected. Given the important prognostic and predictive implications, every gastroesophageal cancer should be tested for MSI.

Expert opinion on management of pancreatic exocrine insufficiency in pancreatic cancer.

Pancreatic exocrine insufficiency (PEI) is a common condition in patients with pancreatic cancer (PC). PEI can be due to the tumor, which, if located in the head, causes obstruction of the pancreatic duct with subsequent atrophy of the pancreatic parenchyma, or it can be the consequence of pancreatic surgical resection. The standard treatment of PEI is pancreatic enzyme replacement therapy (PERT). Clinical data to support the use of PERT in PC are however limited. There are very few randomized clinical trials that evaluated PERT in PC. Most data come from observational studies. Despite this limited clinical evidence, PERT treatment for PEI is an essential part of supportive therapy to ensure optimal nutritional status in PC patients who will receive surgery, neoadjuvant/adjuvant or palliative treatment. The objective of this review is to increase the awareness about PEI in PC patients and to provide expert recommendations on the use of PERT in resected, borderline resectable and unresectable patients, based on clinical experience and literature review.

Evaluation of the fissure sealants applied to erupting permanent molars in accordance to eruption stages: A prospective study.

BACKGROUND: The aim of this study is to evaluate the clinical success of different fissure sealants applied to erupting permanent first molars by taking into consideration the stages of tooth eruption. MATERIALS AND METHODS: Two hundred healthy children between ages 5 and 8 with the inclusion criteria were examined. The erupting permanent first molars were evaluated and those at stage 3 or 4 were selected. An investigator placed three different fissure sealants (giomer, hydrophilic, and hydrophobic resin-based). At the end of 18 months, retention loss, development of new dental caries, localization of retention losses, marginal integrity, and marginal discoloration were evaluated. RESULTS: The rate of tooth with total retention at stage 3 was significantly higher (P < 0.05). The development of dental caries in teeth at stage 4 was found to be significantly higher than that of stage 3 (P < 0.05). In terms of marginal integrity, the difference between stages of tooth eruption is similar (P > 0.05). Regarding marginal discoloration, fissure sealants applied at stage 3 were considered to be more successful than those applied at stage 4 (P < 0.05). CONCLUSIONS: We may conclude that the tooth eruption affects clinical success and giomer-based fissure sealants may not be an alternative for resin-based fissure sealants in erupting teeth.

The PDGFRα-laminin B1-keratin 19 cascade drives tumor progression at the invasive front of human hepatocellular carcinoma.

Human hepatocellular carcinomas (HCCs) expressing the biliary/hepatic progenitor cell marker keratin 19 (K19) have been linked with a poor prognosis and exhibit an increase in platelet-derived growth factor receptor α (PDGFRα) and laminin beta 1 (LAMB1) expression. PDGFRα has been reported to induce de novo synthesis of LAMB1 protein in a Sjogren syndrome antigen B (La/SSB)-dependent manner in a murine metastasis model. However, the role of this cascade in human HCC remains unclear. This study focused on the functional role of the PDGFRα-La/SSB-LAMB1 pathway and its molecular link to K19 expression in human HCC. In surgical HCC specimens from a cohort of 136 patients, PDGFRα expression correlated with K19 expression, microvascular invasion and metastatic spread. In addition, PDGFRα expression in pre-operative needle biopsy specimens predicted poor overall survival during a 5-year follow-up period. Consecutive histological staining demonstrated that the signaling components of the PDGFRα-La/SSB-LAMB1 pathway were strongly expressed at the invasive front. K19-positive HCC cells displayed high levels of α2ß1 integrin (ITG) receptor, both in vitro and in vivo. In vitro activation of PDGFRα signaling triggered the translocation of nuclear La/SSB into the cytoplasm, enhanced the protein synthesis of LAMB1 by activating its internal ribosome entry site, which in turn led to increased secretion of laminin-111. This effect was abrogated by the PDGFRα-specific inhibitor crenolanib. Importantly LAMB1 stimulated ITG-dependent focal adhesion kinase/Src proto-oncogene non-receptor tyrosine kinase signaling. It also promoted the ITG-specific downstream target Rho-associated coiled-coil containing protein kinase 2, induced K19 expression in an autocrine manner, invadopodia formation and cell invasion. Finally, we showed that the knockdown of LAMB1 or K19 in subcutaneous xenograft mouse models resulted in significant loss of cells invading the surrounding stromal tissue and reduced HepG2 colonization into lung and liver after tail vein injection. The PDGFRα-LAMB1 pathway supports tumor progression at the invasive front of human HCC through K19 expression.

Is current perioperative practice in hepatic surgery based on enhanced recovery after surgery (ERAS) principles?

BACKGROUND: The worldwide introduction of multimodal enhanced recovery programs has also changed perioperative care in patients who undergo liver resection. This study was performed to assess current perioperative practice in liver surgery in 11 European HPB centers and compare it to enhanced recovery after surgery (ERAS) principles. METHODS: In each unit, 15 consecutive patients (N = 165) who underwent hepatectomy between 2010 and 2012 were retrospectively analyzed. Compliance was classified as "full," "partial," or "poor" whenever ≥ 80, ≥ 50, or <50 % of the 22 ERAS protocol core items were met. The primary study end point was overall compliance with the ERAS core program per unit and per perioperative phase. RESULTS: Most patients were operated on for malignancy (91 %) and 56 % were minor hepatectomies. The median number of implemented ERAS core items was 9 (range = 7-12) across all centers. Compliance was partial in the preoperative (median 2 of 3 items, range = 1-3) and perioperative phases (median 5 of 10 items, range: 4-7). Median postoperative compliance was poor (median 2 of 9 items, range = 0-4). A statistically significant difference was observed between median length of stay and median time to recovery (7 vs. 5 days, P < 0.001). CONCLUSION: Perioperative care among centers that perform liver resections varied substantially. In current HPB surgical practice, some elements of the ERAS program, e.g., preoperative counselling and minimal fasting, have already been implemented. Elements in the perioperative phase (avoidance of drains and nasogastric tube) and postoperative phase (early resumption of oral intake, early mobilization, and use of recovery criteria) should be further optimized.

The prognostic relevance of tumor hypoxia markers in resected carcinoma of the gallbladder.

BACKGROUND: Intratumoral hypoxia has been suggested to drive more aggressive tumor behavior. Our aim was to define whether markers of tumor hypoxia are predictors of outcome in patients with gallbladder carcinoma. PATIENTS AND METHODS: From 1996 to 2006, 34 patients underwent resection for gallbladder carcinoma. The median follow-up was 12.6 months. Immunohistochemical stains for VEGF, HIF1α, GLUT1, GLUT3, CA9 and EGFR were performed on archival tissue. Immunohistochemical results were correlated with clinical and histopathological parameters. Cumulative overall survival (OS) rates were estimated using the Kaplan-Meier method. Multivariable Cox regression models were used to identify predictors of OS. RESULTS: The median OS was 11.9 (IQR: 3.4-22.0) months. Ubiquitous VEGF staining was observed in all gallbladder carcinomas. High (>50% of tumor cells) EGFR expression was associated with worse OS (p0.03). CA9 expression was less prevalent in poorly differentiated tumors (p0.02). GLUT3, GLUT1 and HIF1α expression were not associated with survival, but did correlate with the presence of lymph node metastasis (p0.02), tumor differentiation (p0.04) and tumor stage (p0.03) respectively. High EGFR expression, TNM stage and preoperative serum CA19.9 were retained as independent predictors of OS in multivariable analysis. CONCLUSION: In gallbladder cancer high expression of EGFR is an independent predictor of survival.

Results of single-probe microwave ablation of metastatic liver cancer.

AIMS: Microwave ablation (MWA) is the most recent development in the field of local ablative therapies. The aim of this study was to evaluate the variability and reproducibility of single-probe MWA vs. radiofrequency ablation (RFA) of liver metastases smaller than 3cm in patients without underlying liver disease. METHODS: Sixteen liver metastases were treated using MWA, and matched for size and localisation with 13 metastases treated by RFA. Tumour diameters and postoperative ablation diameters were recorded (D1 transverse; D2 antero-posterior; D3 cranio-caudal; mm) on computed tomography scans. RESULTS: Median D1, D2, and D3 ablation diameters after MWA vs. RFA were 18.5 (12-64) vs. 34 (16-41)mm (p=0.003), 26 (14-60) vs. 35 (28-40)mm (p=0.046), and 20 (10-73) vs. 32 (20-45)mm (p=0.025), respectively. As compared to RFA, the variability between the lesions after MWA was significantly higher for D2 (p<0.0001) and D3 (p=0.002) but not for D1 (p=0.15). The ablation diameters were less uniform after MWA than after RFA (p<0.001). CONCLUSION: Ablation diameters after single-probe MWA of metastatic liver tumours are highly variable and suboptimal. Improvements are needed before MWA can be implemented routinely.

Hospital cost categories of one-stage versus two-stage management of common bile duct stones.

BACKGROUND: In the era of cost-conscious healthcare, hospitals are focusing on costs. Analysis of hospital costs per cost category may provide indications for potential cost-saving measures in the management of common bile duct stones (CBDS) with gallbladder in situ. METHODS: Between October 2005 and September 2006, 53 consecutive patients suffering from CBDS underwent either a one-stage procedure [laparoscopic common bile duct exploration (LCBDE) with stone clearance and cholecystectomy (LCCE)] or a two-stage procedure [endoscopic retrograde cholangiopancreatography with sphincterotomy and stone clearance (ERCP/ERS) followed by LCCE]. Costs were defined in different cost categories for each activity centre and were linked to the individual patient via the "bill of activities". Only patients (n = 38) with an uneventful post-procedural course and with available cost data were considered for cost analysis. Total length of hospital stay (LOS) was 2 (0-6) days after one-stage and 8 (3-18) days after two-stage procedure (p < 0.0001). RESULTS: Costs per patient were significantly (p < 0.0001) less after one-stage versus two-stage management, i.e. total hospital costs (euro2,636 versus euro4,608), hospitalisation costs (euro701 versus euro2,190), consumables/pharmacy (euro645 versus euro1,476) and para-medical personnel (euro1,035 versus euro1,860; p = 0.0002). Operation room (OR) costs were comparable for one-stage and two-stage management (euro1,278 versus euro1,232; p = 0.280). Total hospital costs during ERCP were euro2,648 (euro729-4,544), during LCCE without LCBDE were euro2,101 (euro1,033-4,269), and during LCCE with LCBDE were euro2,636 (euro1,176-4,235). CONCLUSION: In the management of patients with CBDS and gallbladder in situ a one-stage procedure is associated with significantly less costs as compared with a two-stage procedure. From the economical point of view these patients should preferably be treated via a one-stage procedure as long as safety and efficacy of this approach are provided.

Patterns of recurrence after curative resection of pancreatic ductal adenocarcinoma.

AIMS: Despite curative surgery for pancreatic ductal adenocarcinoma (PDAC), most patients develop cancer recurrence and die from metastatic disease. Understanding of the patterns of failure after surgery can lead to new insights for novel therapeutic modalities. The aim of the present study is to describe the patterns of recurrence after curative resection of PDAC. METHODS: A retrospective analysis was performed of 145 consecutive resections for PDAC between 1998 and 2005 (M/F 75/70; median (range) age 67 years (32-85 y)). The location of the first and consecutive recurrences, and the time interval to cancer recurrence after surgical resection was studied. The magnitude of tumour-free margin was less than a millimetre in 48 patients, whereas a positive surgical margin was observed in 27 patients. The median duration of follow-up was 18.5 (range 0.3-116.8) months. RESULTS: Cancer recurrence was observed in 110 patients. The first location of recurrence was locoregional in 19, extra-pancreatic in 66, and combined locoregional and extra-pancreatic in 25 patients. Extra-pancreatic recurrence developed in the liver in 57, peritoneal in 35, pulmonary in 15, and retroperitoneal in 5 patients. The median (95% CI) overall (OS) and disease-free (DFS) survival was 18.7 (15.7-23.5) and 9.8 (7.5-12.4) months, respectively. The type of cancer recurrence did not significantly influence OS, while the resection margin status had a prognostic effect. CONCLUSION: The vast majority of patients who undergo potentially curative surgery for PDAC develop cancer recurrence located in the abdominal cavity. Surgical resection margins with tumour involvement and tumour-free margins of less then 1mm are negative prognostic factors. Further research on better local surgical control, peri-operative locoregional treatment, and more effective adjuvant systemic therapy is necessary to improve long-term survival of patients with curable PDAC.

Clinical models are inaccurate in predicting bile duct stones in situ for patients with gallbladder.

BACKGROUND: The probability that a patient has common bile duct stones (CBDS) is a key factor in determining diagnostic and treatment strategies. This prospective cohort study evaluated the accuracy of clinical models in predicting CBDS for patients who will undergo cholecystectomy for lithiasis. METHODS: From October 2005 until September 2006, 335 consecutive patients with symptoms of gallstone disease underwent cholecystectomy. Statistical analysis was performed on prospective patient data obtained at the time of first presentation to the hospital. Demonstrable CBDS at the time of endoscopic retrograde cholangiopancreatography (ERCP) or intraoperative cholangiography (IOC) was considered the gold standard for the presence of CBDS. RESULTS: Common bile duct stones were demonstrated in 53 patients. For 35 patients, ERCP was performed, with successful stone clearance in 24 of 30 patients who had proven CBDS. In 29 patients, IOC showed CBDS, which were managed successfully via laparoscopic common bile duct exploration, with stone extraction at the time of cholecystectomy. Prospective validation of the existing model for CBDS resulted in a predictive accuracy rate of 73%. The new model showed a predictive accuracy rate of 79%. CONCLUSION: Clinical models are inaccurate in predicting CBDS in patients with cholelithiasis. Management strategies should be based on the local availability of therapeutic expertise.

Laparoscopic versus open liver resection of hepatic neoplasms: comparative analysis of short-term results.

BACKGROUND: Concerns have been raised regarding outcome after laparoscopic resection of hepatic neoplasms. This prospective study compared morbidity and adequacy of surgical margins in laparoscopic (LLR) versus open liver resection (OLR). METHODS: Outcome in 359 consecutive patients [male/female ratio 187/172; median age 60 years (range 18-84 years)] who underwent partial hepatectomy was analysed. Cirrhosis was present in 32 patients and preoperative chemotherapy was administered in 141 patients. Comparative analyses were performed using propensity scores for all and for matched patients (n=76 per group). RESULTS: Complications occurred in 68/250 (27.2%) patients after OLR and in 6/109 (5.5%) after LLR [odds ratio (OR) 0.16; 95% confidence interval (CI) 0.07-0.37; p<0.0001]. Median intraoperative blood loss was 500 ml (range 10-7,000 ml) in OLR and 100 ml (range 5-4,000 ml) in LLR (p<0.0001). Postoperative hospital stay was 8 days (range 0-155 days) after OLR and 6 days (range 0-41 days) after LLR (p<0.0001). In patients treated for liver malignancy, the surgical resection margin was positive on histopathological examination in 5/237 after OLR and in 1/77 after LLR. The magnitude of the resection margin was 7.5 mm (range 0-45 mm) in OLR and 10.0 mm (range 0-30 mm) in LLR (p=0.087). CONCLUSIONS: LLR for hepatic neoplasms seems to be noninferior to OLR regarding adequacy of surgical margins, and superior to OLR regarding short-term postoperative outcome.

The size of endothelial fenestrae in human liver sinusoids: implications for hepatocyte-directed gene transfer.

Fenestrae allow the passage of gene transfer vectors from the sinusoidal lumen to the surface of hepatocytes. We have previously shown that the diameter of fenestrae correlates with species and strain differences of transgene expression following intravenous adenoviral transfer. In the current study, we demonstrate that the diameter of fenestrae in humans without liver pathology is 107+/-1.5 nm. This is similar to the previously reported diameter in New Zealand White (NZW) rabbits (103+/-1.3 nm) and is significantly smaller than in C57BL/6 mice (141+/-5.4 nm) and Sprague-Dawley rats (161+/-2.7 nm). We show that the diameter of fenestrae in one male NZW rabbit and its offspring characterized by a more than 50-fold increase of transgene expression after adenoviral gene transfer is significantly (113+/-1.5 nm; P<0.001) larger than in control NZW rabbits. In vitro filtration experiments using polycarbonate filters with increasing pore sizes demonstrate that a relatively small increment of the diameter of pores potently enhances passage of adenoviral vectors, consistent with in vivo data. In conclusion, the small diameter of fenestrae in humans is likely to be a major obstacle for hepatocyte transduction by adenoviral vectors.

Yield of routine imaging after curative colorectal cancer treatment.

BACKGROUND/AIM: The use of imaging in the follow-up of patients after curative colorectal cancer resection is much debated. The American Society of Colon and Rectal Surgeons did not recommend routine imaging. This retrospective study assesses the yield of routine imaging to detect recurrent disease. METHODS: In 1998, 108 consecutive patients underwent curative resection for colorectal carcinoma. Minimum followup in our institution was 3 years. Multidisciplinary follow-up at a joint clinic consisted out of a history, clinical examination, serum carcinoembryonic antigen (CEA), chest X-ray and abdominal ultrasound, at least every 6 months. Colonoscopy was performed within 1 year after operation and every 3 to 5 years thereafter. The incidence, timing, means of detection and resectability of recurrence were studied. RESULTS: The recurrence rate was 22% (24 patients): liver metastases (11), extra-hepatic recurrence (10) and combined recurrence (3). Recurrent disease occurred in stage II or III cancer, except for two patients. It was diagnosed at a median of 21.5 months (range 4-79) after surgery. Means of detection were: symptoms in 2 (peritoneal disease, 8%), increasing CEA in 15 (63%), routine imaging in 6 (25%), and abdominal CT-scan in one patient. Curative resection of recurrent disease was possible in ten patients (42%): in 6/15 recurrences detected by CEA, in 3/6 recurrences detected by routine imaging, in 1 liver metastasis detected by CT and in none of the symptomatic patients. CONCLUSIONS: A CEA level increasing above 5.0 microg/L was the most important diagnostic tool. However, one quarter of the recurrences were detected by routine imaging and half of them could be resected for cure. These data support routine imaging during follow-up.

Determinants of complications and adequacy of surgical resection in laparoscopic versus open total gastrectomy for adenocarcinoma.

BACKGROUND: The role of laparoscopic total gastrectomy (LTG) in the treatment of gastric cancer is controversial. The present study analyzed the morbidity and adequacy of resection in LTG versus open total gastrectomy (OTG) for gastric adenocarcinoma. METHODS: Between 2003 and 2006, clinical data of 38 consecutive patients who underwent LTG for gastric adenocarcinoma were collected prospectively. The same data-entry form was used for retrospective data collection from 22 consecutive patients who underwent OTG within the same time period. Logistic regression models were used in univariate and multivariate analyses to identify the optimally combined factors related to the occurrence of postoperative complications and to the number of harvested lymph nodes. RESULTS: Postoperative complications occurred in 24 patients with subsequent mortality in two. Median (range) length of hospital stay was 11 (6-73) days and comparable after LTG versus OTG (p = 0.847). The occurrence of postoperative complications was related (p = 0.004) to the first year of surgery and patients' medical condition before surgery [American Society of Anaesthesiologists (ASA) physical status III]. Microscopic tumor-free margins were obtained in all but two patients. The number of harvested lymph nodes was 17 (0-90), and determined by tumor wall penetration (p = 0.001). CONCLUSIONS: The occurrence of complications after total gastrectomy is determined by the patients' medical condition before surgery and the surgical expertise, but not by the approach. LTG and OTG can result in adequate tumor-free resection margins and lymph node yield, which is related to the tumor wall penetration. The role of LTG in gastric cancer needs further evaluation in randomized controlled trials with large patient series.

Laparoscopic common bile duct stone clearance with flexible choledochoscopy.

BACKGROUND: Laparoscopic common bile duct exploration (LCBDE) is as safe and efficient as endoscopic retrograde cholangiopancreatography (ERCP) in achieving bile duct clearance from stones. No clear guidelines are available on LCBDE with respect to indications for trans-cystic approach versus choledochotomy, or regarding when to use either flexible choledochoscopy (FCD) or intraoperative cholangiography (IOC) guidance. METHODS: From January 2001 until November 2006, 113 consecutive patients with common bile duct stones (CBDS) and gallbladder in situ were enrolled in a prospective non-randomized study to undergo laparoscopic cholecystectomy with LCBDE on an intention-to-treat basis. Twenty-three patients were aged 80 years or older with severe comorbidity. Preoperative ERCP with attempted stone clearance was performed in 24 patients. Laparoscopic common bile duct exploration was attempted for CBDS in the presence of acute cholecystitis in 24 patients. Laparoscopic common bile duct exploration was performed via the trans-cystic approach in 83 patients and via choledochotomy in 30 patients. Flexible choledochoscopy was used in 79 patients and IOC guidance in 34 patients. RESULTS: No mortality occurred. Postoperative complications were encountered in nine patients. Laparoscopic stone clearance of the bile duct was successful in 91.8% of the patients. Median length of hospital stay (LOS) was two days (range, 0 to 24 days) after trans-cystic LCBDE and six days (range, 2 to 34 days) after stone clearance via choledochotomy (p < 0.0001). Choledochotomy was performed for CBDS measuring an average of 11.5 mm (range, 5 to 30 mm) in diameter while trans-cystic LCBDE was successful for stones measuring an average of 5 mm (range, 2 to 14 mm) (p < 0.0001). Mean duration of surgery was 75 minutes (range, 30 to 180 minutes) when FCD was used, and 107 minutes (range, 45 to 240 minutes) in patients undergoing LCBDE under IOC guidance (p < 0.0001). CONCLUSION: Laparoscopic cholecystectomy and LCBDE with stone extraction can be performed with high efficiency, minimal morbidity and without mortality. A trans-cystic approach is feasible in most patients, whereas choledochotomy should be restricted to large bile duct stones that cannot be extracted through the cystic duct. The use of flexible choledochoscopy is preferable to IOC guidance.

Hospital cost-categories of pancreaticoduodenectomy.

AIMS: In the era of cost-conscious healthcare, hospitals are focusing on costs. Analysis of hospital costs per cost-category may provide indications for potential cost saving measures in pancreaticoduodenectomy (PD). METHODS: Between January 2004 and June 2005, 109 consecutive patients underwent curative PD for a pancreatic or peri-ampullary tumour. Costs were defined in different cost categories for each activity centre and were linked to the individual patient via the 'bill of activities'. RESULTS: Postoperative complication rate was 46.8%, postoperative pancreatic fistula (POPF) 12.8%, and mortality rate 1.8%. The overall median LOS was 17 (range 7-52) days. The length of hospital stay (LOS) was significantly (p < 0.0001) different between patients with POPF, those with other complications, and patients without complications i.e. 26 (10-36) vs. 21 (8-52) vs. 14 (7-33) days, respectively. Median hospital cost per patient was 10406 (5570-30999) euros. The total hospital costs were significantly related to the LOS (p < 0.0001). The increase of total hospital costs was influenced by the hospitalization (p < 0.0001) and medical staff (p < 0.0001) costs, but not by the cost for the operation room (p = 0.233). CONCLUSION: Postoperative complications, in particular POPF, are associated with increased LOS and higher hospital costs. Any measure to reduce the incidence and severity of complications after PD will save hospital costs.

Effect of centralization of pancreaticoduodenectomy on nationwide hospital mortality and length of stay.

BACKGROUND: Despite the persistence of large differences in operative mortality rates between centres, the value of centralization of pancreaticoduodenectomy (PD) remains under debate. This cohort study analysed the effect of centralization of PD on nationwide hospital mortality and length of hospital stay in Belgium. METHODS: Data on in-hospital mortality and duration of hospital stay after PD from 2000 to 2004 were obtained from the Belgian national registry database. Analysis of mortality and hospital stay was based on 1842 PDs from all 126 hospitals. Logistic regression analysis was used to assess the effect of patient referral on the national mortality rate. RESULTS: The national mortality rate was 8.4 per cent and the median duration of hospital stay after operation was 21.6 (range 3-117) days. There was a significant relationship between the annual number of PDs per hospital and both mortality rate (P = 0.005) and hospital stay (P = 0.027). Application of a cut-off volume of ten PDs per year per centre would necessitate 56.8 per cent of all patients being referred, resulting in an expected national mortality rate of 6.0 per cent. CONCLUSION: Referral of patients to more experienced centres for PD is expected to result in a significant reduction in hospital mortality rate and duration of hospital stay, regardless of the experience of the referring centre. Action towards centralization should be undertaken nationwide.

Laparoscopic intrahepatic Glissonian approach for right hepatectomy is safe, simple, and reproducible.

BACKGROUND: Hemorrhage from portal and hepatic veins is a major concern with laparoscopic right hepatectomy (LRH). The standard hilar approach is dissection of the portal pedicle outside the liver parenchyma with separate transection of the right hepatic artery, portal vein, and bile duct. Variations in anatomy can hamper vascular and biliary control. The intrahepatic Glissonian access avoids these risks by en masse ligation of the portal structures without dissection for each separately. This technique was performed laparoscopically for the last 2 among 10 LRHs, and the results are presented. METHODS: Total LRH was performed under ultrasound assistance for two patients with malignancy. After lymph node sampling at the hepatoduodenal ligament, dissection was started with the incision of liver parenchyma posterior and anterior to the hilum, then continued outside the portal pedicle bifurcation toward the right and left sheaths. An endoscopic vascular stapling device was placed to transect the right portal pedicle en masse under direct laparoscopic vision and cholangiography guidance. Parenchymal transection and vascular control of the right hepatic vein was accomplished with harmonic scalpel, cavitron ultrasonic aspirator, bipolar diathermy, clips, and endoscopic stapling device, as appropriate. No Pringle's maneuver was used. The specimen was extracted through a suprapubic incision using an endobag. RESULTS: The operative times for the two patients were, respectively, 180 and 240 min. No blood loss occurred during the intrahepatic Glissonian dissection. Intraoperative blood loss (from the right hepatic vein) of 700 and 800 ml, respectively, was controlled laparoscopically. The postoperative periods were uneventful, with discharge, respectively, on days 6 and 7. The surgical resection margins were free of tumor. CONCLUSIONS: The laparoscopic intrahepatic Glissonian approach used for right hepatectomy is safe, simple, and reproducible. It facilitates the hepatic hilar dissection with minimal operative risk. Further implementation of this technique is encouraged to improve the outcome for patients undergoing laparoscopic liver resection.