Search

Background: Many centers worldwide are shifting from laparoscopic to robotic minimally invasive hepato-pancreato-biliary resections (MIS-HPB) but large single center series assessing this process are lacking. We hypothesized that the introduction of robot-assisted surgery was safe and feasible in a high-volume center. Methods: Single center, post-hoc assessment of prospectively collected data including all consecutive MIS-HPB resections (January 2010–February 2022). As of December 2018, all MIS pancreatoduodenectomy and liver resections were robot-assisted. All surgeons had participated in dedicated training programs for laparoscopic and robotic MIS-HPB. Primary outcomes were in-hospital/30-day mortality and Clavien-Dindo ≥ 3 complications. Results: Among 1875 pancreatic and liver resections, 600 (32%) were MIS-HPB resections. The overall rate of conversion was 4.3%, Clavien-Dindo ≥ 3 complications 25.7%, and in-hospital/30-day mortality 1.8% (n = 11). When comparing the period before and after the introduction of robotic MIS-HPB (Dec 2018), the overall use of MIS-HPB increased from 25.3 to 43.8% (P < 0.001) and blood loss decreased from 250 ml [IQR 100–500] to 150 ml [IQR 50–300] (P < 0.001). The 291 MIS pancreatic resections included 163 MIS pancreatoduodenectomies (52 laparoscopic, 111 robotic) with 4.3% conversion rate. The implementation of robotic pancreatoduodenectomy was associated with reduced operation time (450 vs 361 min; P < 0.001), reduced blood loss (350 vs 200 ml; P < 0.001), and a decreased rate of delayed gastric emptying (28.8% vs 9.9%; P = 0.009). The 309 MIS liver resections included 198 laparoscopic and 111 robotic procedures with a 3.6% conversion rate. The implementation of robotic liver resection was associated with less overall complications (24.7% vs 10.8%; P = 0.003) and shorter hospital stay (4 vs 3 days; P < 0.001). Conclusion: The introduction of robotic surgery was associated with greater implementation of MIS-HPB in up to nearly half of all pancreatic and liver resections. Although mortality and major morbidity were not affected, robotic surgery was associated with improvements in some selected outcomes. Ultimately, randomized studies and high-quality registries should determine its added value. Graphical Abstract: [Figure not available: see fulltext.]

In the original article Moritz Schmelzle’s last name is spelled wrong. It is correct as reflected here.

Background Preoperative portal vein embolization (PVE) is frequently used to improve future liver remnant volume (FLRV) and to reduce the risk of liver failure after major liver resection. Objective This paper aimed to assess postoperative outcomes after PVE and resection for suspected perihilar cholangiocarcinoma (PHC) in an international, multicentric cohort. Methods Patients undergoing resection for suspected PHC across 20 centers worldwide, from the year 2000, were included. Liver failure, biliary leakage, and hemorrhage were classified according to the respective International Study Group of Liver Surgery criteria. Using propensity scoring, two equal cohorts were generated using matching parameters, i.e. age, sex, American Society of Anesthesiologists classification, jaundice, type of biliary drainage, baseline FLRV, resection type, and portal vein resection. Results A total of 1667 patients were treated for suspected PHC during the study period. In 298 patients who underwent preoperative PVE, the overall incidence of liver failure and 90-day mortality was 27% and 18%, respectively, as opposed to 14% and 12%, respectively, in patients without PVE (p p = 0.005). After propensity score matching, 98 patients were enrolled in each cohort, resulting in similar baseline and operative characteristics. Liver failure was lower in the PVE group (8% vs. 36%, p p p = 0.01), and 90-day mortality (7% vs. 18%, p = 0.03). Conclusion PVE before major liver resection for PHC is associated with a lower incidence of liver failure, biliary leakage, abscess formation, and mortality. These results demonstrate the importance of PVE as an integral component in the surgical treatment of PHC.

Background: Limited evidence exists to guide the management of patients with liver metastases from squamous cell carcinoma (SCC). The aim of this retrospective multicentre cohort study was to describe patterns of disease recurrence after liver resection/ablation for SCC liver metastases and factors associated with recurrence-free survival (RFS) and overall survival (OS). Method: Members of the European-African Hepato-Pancreato-Biliary Association were invited to include all consecutive patients undergoing liver resection/ablation for SCC liver metastases between 2002 and 2019. Patient, tumour and perioperative characteristics were analysed with regard to RFS and OS. Results: Among the 102 patients included from 24 European centres, 56 patients had anal cancer, and 46 patients had SCC from other origin. RFS in patients with anal cancer and non-anal cancer was 16 and 9 months, respectively (P = 0.134). A positive resection margin significantly influenced RFS for both anal cancer and non-anal cancer liver metastases (hazard ratio 6.82, 95 per cent c.i. 2.40 to 19.35, for the entire cohort). Median survival duration and 5-year OS rate among patients with anal cancer and non-anal cancer were 50 months and 45 per cent and 21 months and 25 per cent, respectively. For the entire cohort, only non-radical resection was associated with worse overall survival (hazard ratio 3.21, 95 per cent c.i. 1.24 to 8.30). Conclusion: Liver resection/ablation of liver metastases from SCC can result in long-term survival. Survival was superior in treated patients with liver metastases from anal versus non-anal cancer. A negative resection margin is paramount for acceptable outcome.

Otto Lanz (1865-1935) was a Swiss surgeon trained by Theodore Kocher in Berne. In 1902, he was invited to become professor of surgery at the Binnengasthuis hospital in Amsterdam. He was an outstanding surgeon who was well known for his surgery of the thyroid gland and the appendix. He introduced the eponymous Lanz's point in acute appendicitis and also the girdle incision for appendectomy. He was a strong proponent of 'early' appendectomy, as opposed to the conservative approach, at that time the treatment of choice. He was a great connoisseur and passionate collector of Italian Renaissance art. His Italian works of art have been exhibited in a special 'Lanz Hall' at the Rijksmuseum in Amsterdam. During World War II, his collection was acquired for Hitler's proposed Führermuseum but was returned to Amsterdam after the war. A portrait by Jan Toorop and Lanz's former villa on the Museum Square in Amsterdam remind us of this colourful surgeon.

Background Distal pancreatectomy with celiac axis resection (DP-CAR) is a treatment option for selected patients with pancreatic cancer involving the celiac axis. A recent multicenter European study reported a 90-day mortality rate of 16%, highlighting the importance of patient selection. The authors constructed a risk score to predict 90-day mortality and assessed oncologic outcomes. Methods This multicenter retrospective cohort study investigated patients undergoing DP-CAR at 20 European centers from 12 countries (model design 2000–2016) and three very-high-volume international centers in the United States and Japan (model validation 2004–2017). The area under receiver operator curve (AUC) and calibration plots were used for validation of the 90-day mortality risk model. Secondary outcomes included resection margin status, adjuvant therapy, and survival. Results For 191 DP-CAR patients, the 90-day mortality rate was 5.5% (95 confidence interval [CI], 2.2–11%) at 5 high-volume (≥ 1 DP-CAR/year) and 18% (95 CI, 9–30%) at 18 low-volume DP-CAR centers (P = 0.015). A risk score with age, sex, body mass index (BMI), American Society of Anesthesiologists (ASA) score, multivisceral resection, open versus minimally invasive surgery, and low- versus high-volume center performed well in both the design and validation cohorts (AUC, 0.79 vs 0.74; P = 0.642). For 174 patients with pancreatic ductal adenocarcinoma, the R0 resection rate was 60%, neoadjuvant and adjuvant therapies were applied for respectively 69% and 67% of the patients, and the median overall survival period was 19 months (95 CI, 15–25 months). Conclusions When performed for selected patients at high-volume centers, DP-CAR is associated with acceptable 90-day mortality and overall survival. The authors propose a 90-day mortality risk score to improve patient selection and outcomes, with DP-CAR volume as the dominant predictor. Electronic supplementary material The online version of this article (10.1245/s10434-018-07101-0) contains supplementary material, which is available to authorized users.

Biliary tract carcinoma (BTC) comprises gallbladder and intra-/extrahepatic cholangiocarcinoma (GBC, ICC, EHC), which are currently classified by anatomical origin. Better understanding of the mutational profile of BTCs might refine classification and improve treatment. We performed a systematic review of studies reporting on mutational profiling of BTC. We included articles reporting on whole-exome/whole-genome-sequencing (WES/WGS) and targeted sequencing (TS) of BTC, published between 2000-2017. Pooled mutation proportions were calculated, stratified by anatomical region and sequencing technique. A total of 25 studies with 1806 patients were included. Overall, TP53 was the most commonly mutated gene in BTC. GBC was associated with mutations in PFKFB3, PLXN2 and PGAP1. Mutations in IDH1, IDH2 and FGFR fusions almost exclusively occurred in ICC patients. Mutations in APC, GNAS and TGFBR2 occurred exclusively in EHC patients. In conclusion, subtypes of BTCs exhibit minor differences in mutational profile, which is likely influenced by the cell of origin.

[This corrects the article DOI: 10.1371/journal.pone.0166987.]

Preoperative biliary drainage (PBD) is used routinely in the evaluation of patients with potentially resectable perihilar cholangiocarcinoma to relieve cholestasis and improve the liver's resilience to surgery. Little preclinical or translatational data are, however, currently available to guide the use of PBD in this patient group. The effect of PBD on hepatic gene expression profiles was therefore studied by microarray analysis. Drainage affects inflammatory and fibrotic gene signatures.

Photodynamic therapy for therapy-resistant cancers will greatly benefit from targeted delivery of tumor photosensitizing agents. In this study, a strategy for the site-specific conjugation of single domain antibodies onto liposomes containing the photosensitizer zinc phthalocyanine was developed and tested.

Between around 1620 and the end of the eighteenth century, every surgeon working in Amsterdam was presented with a guild medal on passing their surgeon's exams. These medals actually represented membership of the Surgeon's Guild of Amsterdam and could be used as proof of attendance at meetings of the Guild. From 1864 onwards surgeons also received the Hortus medal, which allowed them entry to the Hortus Medicus. Less common medals include medals for ensuring the surgeon's apprentices attended lectures, funeral medals for ensuring correct procedures regarding casket bearing duties were followed at a funeral, and medals of honour recognising services to the Guild. The collection of 17th and 18th century Amsterdam Surgeon's Guild medals numbers some 230 examples, and is the largest and most varied collection of its kind in the world. A few of the medals that have been preserved actually belonged to surgeons depicted in the famous series of group portraits. We examined who these surgeons were and what the purpose of these medals was

This review is to summarize the current knowledge about preoperative biliary drainage (PBD) in patients with biliary obstruction caused by pancreatic cancer. Most patients with pancreatic carcinoma (85%) will present with obstructive jaundice. The presence of toxic substances as bilirubin and bile salts, impaired liver function and altered nutritional status due to obstructive jaundice have been characterized as factors for development of complications after surgery Whereas PBD was to yield beneficial effects in the experimental setting, conflicting results have been observed in clinical studies. The meta-analysis from relative older studies as well as more importantly a recent clinical trial showed that PBD should not be performed routinely. PBD for patients with a distal biliary obstruction is leading to more serious complications compared with early surgery. Arguments for PBD have shifted from a potential therapeutic benefit towards a logistic problem such as patients suffering from cholangitis and severe jaundice at admission or patients who need extra diagnostic tests, or delay in surgery due to a referral pattern or waiting list for surgery as well as candidates for neoadjuvant chemo(radio)therapy. If drainage is indicated in these patients it should be performed with a metal stent to reduce complications after the drainage procedure such as stent occlusion and cholangitis. Considering a change towards more neoadjuvant therapy regimes improvement of the quality of the biliary drainage concept is still important

Purpose: Preoperative radiological assessment of hepatic steatosis is recommended in patients undergoing a liver resection, but few studies investigated the diagnostic accuracy after neoadjuvant chemotherapy. The aim of this study was to compare diagnostic accuracy of preoperative CT or MRI measurements of steatosis in patients with colorectal liver metastases after induction chemotherapy. Methods: MRI measurements (relative signal intensity decrease; RSID), N = 36, and CT scan measurements (Hounsfield units; HU), N = 32, were compared with histological steatosis assessment. Diagnostic accuracy was determined for detecting any (> 5%) or marked macrovesicular steatosis (> 33%). Results: MRI showed the highest correlation with histology (r = 0.82, P

OBJECTIVE : To determine the result of surgical treatment of patients with hilar cholangiocarcinoma (HCCA) before and after the transition from predominantly local bile duct resections to more extensive resections including partial liver resection in order to achieve complete tumour resection in the Academic Medical Center, Amsterdam (The Netherlands). DESIGN: Retrospective and descriptive. METHODS : In the period 1988-2003, 117 consecutive patients underwent resection due to suspected HCCA. Preoperative work-up included staging laparoscopy, preoperative biliary drainage and short-course radiation therapy (3 x 3.5 Gy) to prevent seeding metastases. A more extended multidisciplinary surgical approach combining bile duct resection with partial liver resection was applied as of 1998. Outcomes of resection including 5-year survival were assessed in patients who had undergone resection before (1988-1997; period 1) and after (1998-2003; period 2) this change in surgical approach. RESULTS : In 18 patients (15.3%) a benign lesion was found in the resection specimen. Among the other 99 patients with microscopically confirmed HCCA, 21 (72%) of 29 patients had undergone bile duct resection in combination with partial liver resection in period 2 as compared to 17 (24%) of 70 patients in period 1. The margin tumour free resection rate increased from 20% in period 1 to 59% in period 2. Five-year survival increased from 20% (SE: 5) in period 1, to 33% (SE: 9) in period 2. Morbidity and mortality in period 2 were 69% and 10%, respectively, as compared to 64% and 17% in period 1. CONCLUSION : More extensive resection of HCCA in combination with partial liver resection in the setting of a multidisciplinary approach led to a higher rate of margin free resections and improved 5-year survival

In a 59-year-old woman with pain in the right upper abdomen, echography and CT-scan revealed adenomatosis of the gallbladder. Her symptoms did not disappear after cholecystectomy, even though echography showed no further abnormality. In a 46-year-old man with fever and weight loss, echography revealed two polyps in the gallbladder. Following cholecystectomy, histopathology revealed cholesterol polyps and an infection with Entamoeba coli. In a 63-year-old man with systemic symptoms, a biopsy of the echographically diagnosed tumour of the gallbladder revealed that he had actually had cholecystitis. The management was wait-and-see and the patient recovered completely. In a 68-year-old woman with jaundice and attacks of abdominal pain, a CT-scan revealed gallstones. The symptoms recurred following an ERCP. Following cholecystectomy, an adenocarcinoma of the gallbladder was found. One year later, a contact metastasis developed forwhich she received radiotherapy. After 4 years she was in good condition. Patients with a tumour in the gallbladder are often diagnosed with gallbladder cancer, which has a poor prognosis. Other diseases should also be considered, since the treatment and prognosis differ greatly. It is important to differentiate at an early stage. Ultrasound, CT and MRI have improved the possibility of differentiating and choosing the correct treatment

The recommendation of Van der Windt et al. in this issue that the diagnosis 'hepatocellular adenoma' can be made only on the basis of imaging studies should be applied with caution. Tissue diagnosis remains the gold standard. Although the real risk of malignant degeneration of hepatocellular adenoma remains unknown, there is agreement that preventive excision is indicated when the size is > 5 cm. In case of bleeding from a hepatocellular adenoma, selective embolisation of the proper hepatic artery is effective. Secondary resection of the adenoma following bleeding is not always necessary. The withdrawal of oral contraceptives is the first recommendation after a diagnosis of hepatocellular adenoma is made, which is often followed by regression of the tumour. The elective embolisation of a hepatocellular adenoma via the hepatic artery is a new, promising form of treatment that can lead to regression. The recommendations made in the article constitute a good point of departure for a national discussion

BACKGROUND: The therapeutic approach to patients with chronic pancreatitis (CP) is complicated by the fact that patients are presented to the physician at different stages of disease and in the presence of varying clinical symptoms. Generally, an expectant approach is justified for patients with asymptomatic CP. At present, patients with symptoms related to gland destruction are initially treated by endoscopic means, while surgical treatment of CP is usually reserved for intractable abdominal pain, suspicion of cancer, and complications such as persistent pseudocysts. AIM: To review the studies currently available evaluating surgical and/or endoscopic management of CP. RESULTS: Improvements in imaging techniques, as well as a better understanding of the pathophysiology of CP and mechanisms causing pain, have led to a more conscious selection of patients for surgery. Type of surgery depends on whether the pancreatic duct is dilated, presence of an inflammatory mass and occurrence of complications (pseudocysts, gastric outlet obstruction). Eventually, after initial endoscopic treatment, a substantial number of patients still need surgery for persistent complaints. CONCLUSIONS: For patients with symptomatic CP, a multidisciplinary approach is indicated with low threshold to surgical intervention, since long-term pain relief is accomplished more often after surgical treatment than after endoscopic treatment

BACKGROUND: Surgical treatment of hilar cholangiocarcinoma (Klatskin tumours) is difficult because of its central location in the liver hilum. Recent developments in surgical techniques have improved the outcome after resection. AIM: To describe the surgical approaches currently applied in our centre and the impact of these strategies on outcome and criteria for resection. METHODS: From 1988 to 2003, 99 consecutive patients underwent resection for hilar cholangiocarcinoma. Patients were analysed for rate of R0 resections in relation with Bismuth classification. Morbidity, mortality and survival were assessed. RESULTS: The rate of hilar resections in combination with (extended) liver resections for type III and IV tumours increased from 24% to 95% in the last 5 years of the study period. Eight patients (8%) had Bismuth type IV tumours. Four of these patients underwent palliative local excisions of the hepatic duct confluence whereas the other four patients underwent hilar resection in combination with partial liver resection, resulting in microscopically radical resections. There was no mortality in this group. Overall postoperative morbidity and mortality were 68% and 10%, respectively. CONCLUSIONS: An aggressive surgical approach consisting of hilar resections combined with partial liver resections including segments 1 and 4, resulted in a higher rate of R0 resections. Even Bismuth type IV tumours may be resectable depending on the biliary anatomy of the hepatic duct confluence

OBJECTIVE: To analyse the volume-outcome effect of pancreatic surgery by means of a systematic review, and to determine the effect of the ongoing plea for centralisation of pylorus-preserving pancreaticoduodenectomy in the Netherlands. DESIGN: Systematic review and retrospective evaluation. METHOD: A systematic search for studies comparing hospital mortality rates after pancreatic resection in high- and low-volume hospitals was conducted. The studies were independently assessed regarding design, inclusion criteria, threshold value for high and low volume and primary hospital mortality outcome. Data were obtained from the Dutch nation-wide registry on the mortality outcome of pancreaticoduodenectomy in 1994-2003. Hospitals were divided into 4 categories based on the number of pancreaticoduodenectomies performed. The effect of the ongoing plea for centralisation was analysed. RESULTS: Twelve observational studies comprising a total of 19,688 patients were included. Because the studies were too heterogeneous to allow a meta-analysis, a qualitative analysis was performed. The relative risk of dying in a high-volume hospital compared with a low-volume hospital was between 0.07 and 0.76 and was inversely proportional to the arbitrarily defined volume cut-off values. Various analyses conducted over a to-year period in the Netherlands reported mortality rates of 14-17% in hospitals that performed fewer than 5 pancreaticoduodenectomies per year, compared with rates of 0.0-3.50 degrees h in hospitals that performed more than 24 pancreaticoduodenectomies per year. The percentage of patients undergoing surgery in hospitals with a volume less than ro pancreaticoduodenectomies per year was 57% in 2000-2003 (454/792), compared with 65% (280/428) in 1994-1995. CONCLUSION: This systematic review provided evidence of an inverse relationship between hospital volume and mortality after pancreaticoduodenectomy and confirmed the value of centralisation of this procedure in high-volume hospitals. The 10-year-long plea of the Dutch surgical community for quality assessment and, if necessary, centralisation has not resulted in a reduction in mortality rates after pancreatic resection or a change in referral patterns in The Netherlands

OBJECTIVES: The University of Wisconsin solution (UW) is the gold standard for cold storage (CS) of donor livers. However, UW contains the colloid Hydroxyethyl starch (HES), which may cause perfusion deficits due to its high viscosity. Recently, a new CS preservation solution, Hypothermosol (HTS), was introduced which contains the less viscous colloid Dextran. The aim of this study was to assess HTS as a cold storage solution for preservation of the liver. METHODS: In an isolated perfused rat liver model, hepatocellular damage was assessed after 24 hours of CS. Liver enzymes were measured during reperfusion with Krebs-Henseleit Buffer. Bile was collected during reperfusion as a parameter of liver function. RESULTS: CS using HTS showed a significant decrease of ALT and LDH levels (as compared to UW) at all time points during reperfusion. For LDH these results where most pronounced at t=10 min (84 +/- 7.09 vs 113 +/- 7.57: p < 0.05) and t=30 min (149.2 +/- 9.68 vs 194 +/-6.52: p

OBJECTIVE: To provide an embryological explanation for the presence of ovarian stroma in cystadenomas of the liver and pancreas. DESIGN: Investigation of patients and embryos. METHOD: From 1997 to 2001 in the Academic Medical Centre, Amsterdam, the Netherlands, nine women were treated for a cystadenoma with ovarian stroma, six of which were situated in the liver and three in the tail of pancreas. In one patient with a cystadenoma in the liver, malignant changes had taken place. In embryos at 5-8 weeks development, the regional differences in the morphology of the epithelium of the peritoneal cavity and the position of the gonads in relation to the embryonic liver, pancreas and spleen were examined. RESULTS: In the foetal period before the gonads begin to descend, they are situated directly dorsal to the liver, tail of pancreas and spleen, but are separated from these by the peritoneal cavity. The cells that cover the urogenital folds distinguish themselves from those elsewhere in the peritoneal cavity as they are bulging in shape as opposed to flattened. This activated morphology suggests that on physical contact with a neighbouring organ the cells covering the gonads may become detached and lodge in that organ. CONCLUSION: It is likely that cystadenomas of the liver and pancreas have their origin in the cells that cover the embryonic gonads. The anomalous morphology of these covering cells in fact suggests that they are relatively easily mobilized. They are probably comparable with inoculation metastasis in the coelomic cavity. Taking the chance of malignant transformation of a cystadenoma into account, the treatment of choice is radical resection of the abnormality.

Obstructive jaundice occurred in 3 patients, 2 women, aged 44 and 60 years, and one man aged 62 years: 17 years after choledochojejunostomy following a complicated cholecystectomy, 8 years after hepatojejunostomy following choledochal cyst removal, and 1 year after laparoscopic cholecystectomy. Percutaneous or endoscopic stent placement was performed in all patients to relieve biliary obstruction. However, stent dysfunction repeatedly resulted in re-stenting of the obstruction. Imaging techniques, as well as endoscopic brush pathology could not distinguish between a benign or malignant stenosis. Explorative laparotomy showed a new growth in all 3 patients, of which 2 were malignant. When obstructive jaundice occurs after surgery of the biliary tract for benign disease, the most likely cause is a benign stenosis. Percutaneous or endoscopic stenting is the treatment of choice. In case of unexpected and/or repeated stent failure, when a diagnosis cannot be made due to inconclusive imaging or pathology of the stenosis exploratory surgery should be considered, as malignant stenosis may be present

Machine perfusion systems for continuous hypothermic perfusion preservation are computer controlled and re-usable. The system of perfusion preservation proved beneficial for for storage of kidneys, particularly those harvested from NHBD donors. The first disposable continuous hypothermic perfusion system which can be used for storage of livers is presented

Survival data of patients with pancreatic carcinoma are often overestimated because of incomplete follow-up. Therefore, the aim of this study was to approach complete follow-up and to analyse survival and prognostic factors of patients who underwent surgical treatment for pancreatic adenocarcinoma. Between 1992 and 2002, 343 patients underwent surgical treatment for pancreatic adenocarcinoma. One hundred and sixty patients underwent a resection with a curative intention and 183 patients underwent bypass surgery for palliation. Follow-up was complete for 93% of patients. Median survival after resection and bypass was 17.0 and 7.5 months, and 5-year survival was 8% and 0, respectively. In multivariate analysis, tumour-positive lymph nodes, non-radical surgery, poor tumour differentiation, and tumour size were independent prognostic factors for survival after resection. For patients treated with bypass surgery, metastatic disease and tumour size independently predicted survival. In conclusion, actual survival of patients with pancreatic adenocarcinoma is disappointing compared with the actuarial survival rates reported in the literature. The independent prognostic factors for survival of patients who underwent surgical treatment for pancreatic adenocarcinoma are tumour-related. (C) 2003 Elsevier Ltd. All rights reserved

OBJECTIVES: The effect of topical vascular endothelial growth factor (VEGF) on post-surgical tracheal healing using various reconstruction materials was studied, with particular regard to prevention of granulation tissue or fibrosis.METHODS: Twenty-four New Zealand White rabbits underwent survival surgery using autograft patches (n=6), xenopericardium patches (n=6), intraluminal Palmaz wire stents (n=6), and controls (n=6). Autograft and pericardial half-patches were soaked in topical VEGF (5 microg/ml over 30 min) and saline before reimplantation. Stents and controls received circumferential injections of VEGF and saline in the tracheal wall. At 1-4 months postoperatively, specimens of sacrificed animals were stained with anti-VEGF antibody, followed by morphological and immunohistochemical examination.RESULTS: Rabbits with autografts and controls fared well until planned sacrifice. After xenopericardium repair, obstructive intraluminal granulation tissue led to early sacrifice in three rabbits. Stent insertion led to earlier death from airway obstruction in all six rabbits. Topical VEGF reduced granulation tissue after pericardial repair and fibrosis in all repairs except in stents. Remarkably, VEGF-pretreated half-patches and saline half-patches stained similarly high for VEGF, suggesting also local production of VEGF, probably in plasmacells, and in submucosal glands.CONCLUSIONS: Autograft repair induces the least granulation tissue and fibrosis, and the best healing pattern. Stents rapidly induced critical airway obstruction, unhindered by VEGF, leading to premature death. Tracheal pretreatment with topical VEGF reduces postoperative fibrosis after autograft and pericardial patch repairs, and reduces granulation tissue after xenopericardium repair. In time, VEGF is probably locally produced, although its potential role in tracheal healing remains to be established.

Women have been members of the surgical guilds since as early as the 14th century. Decrees dating from the 16th-18th centuries demonstrate that a number of women made a living through surgical practice at that time. From the Middle Ages through to the 18th century, women played their role in medical practice, and were also involved in surgery. Apart from the common problems of the profession, these female practitioners also encountered difficulties related to their gender

Hector Treub (1856-1920), initially a surgeon trained by Van Iterson in Leiden, was appointed as professor in Gynaecology and Obstetrics in Leiden in 1887, and in 1896 he took on this position at the University of Amsterdam. He was a strong proponent of women training as medical specialists at a time where higher education for women was a matter of public debate. Treub was the first medical professor in the Netherlands who trained women in a surgical specialty, Heleen Brouwer-Robert (1887-1979), Rosalie Wijnberg (1887-1973) and Jeanne Knoop (1890-1975) were trained by him as surgically educated gynaecologists. Frieda van Hasselt (1891-1979) was trained by Van Rooy (1880-1937), former assistant and successor of Treub. These four women were the first female members of the Dutch Surgical Association, having joined this association during their surgical training.