ABSTRACT. Ch. HOLEMANS , H. VAN DAMME and J.O. DEFRAIGNE Department of CardioVascular Surgery , CHU de Liège.

Background : Cryopreserved arterial allografts have gained increasing interest as a vascular substitute in the management of vascular infection and limb salvage revascularisation in the absence of adequate autologous saphenous vein. The initial enthusiasm in the use of cryopreserved arterial allografts was subsequently tempered by suboptimal long-term outcome. Thrombosis, recurrent intestinal fistulisation, anastomotic pseudo- aneurysm, allograft disruption, aneurysmal degeneration and persistent infection have been frequently reported in series with long term follow-up. Methods and results:

The authors report their experience with 132 cryopreserved allografts inserted in 123 patients between July 2000 and July 2015. It concerned 78 patients with infected vascular prosthesis (group 1) , 9 patients with an aorto-enteric fistula (group 2), 9 patients with infectious arteritis (group 3) and 27 patients with critical limb ischemia (group 4).

The in-hospital mortality was 9.41% for group 1, 30.0 % for group 2, 0% for group 3 and 6.89% for group 4. Mean follow-up was 59 months. Allograft-related re-interventions were necessary in 29.41% of group 1, 45% of group 2, 0% of group 3 and 34.50 % of group 4.

The 5-year patency rate was 80% in group 1, 45% in group, 100% in group 3 and 24% in group 4.

The 5 year survival attained 52.85% for group 1, 44.0 % for group 2, 90.0 % for group 3 and 40.0 % for group 4. Conclusions: Implantation of arterial allografts is characterised by inherent allograft-related complications and suboptimal outcome results. Nevertheless, cryopreserved arterial allografts remain the first choice treatment modality to eradicate major vascular infections . For critical limb ischemia, the poor results do not longer justify the use of cryopreserved arterial allografts. The authors discuss the allograft-related complications and suggest some tricks to minimize their risk.

ABSTRACT. OBJECTIVE. Shunting during carotid endarterectomy (CEA) remains controversial. Assessment of shunting should be based on measuring cerebral ischemia. Diffusion-weighted magnetic resonance imaging (DWI) is increasingly used to identify cerebral ischemia. In this study, we assess the role of shunting in the occurrence of cerebral embolization during CEA, as detected by DWI. METHODS. 366 CEA procedures, with a policy of selective shunting, were included in this retrospective cohort study for a period of 7 years. Data on shunt use, perioperative neurological events and postoperative DWI were collected. Primary outcome measure was the incidence of emboligenic DWI lesions ipsilateral to the side of surgery. The incidence of these lesions was compared between the shunting and the non-shunting group. Subgroup analysis was performed to differentiate between asymptomatic and symptomatic carotid stenosis. RESULTS. The overall incidence of emboligenic DWI lesions is 8.7% (32/366). In the non-shunting group (n=280), a 7.1% incidence is reported, whereas in the shunting group (n=86), a 14.0% incidence is seen (p=0.08). In the asymptomatic group, there were significantly more emboligenic DWI lesions when using a shunt, compared to no shunting (16.3% vs. 5.7% incidence, respectively; p=0.03). In the symptomatic group, no difference in incidence of emboligenic DWI lesions was found when a shunt was used or not (10.8% vs. 9.6%; p=0.76). One patient with an emboligenic DWI lesion presented with a stroke; all other lesions were clinically silent (31/32; 97%). CONCLUSIONS. There is a tendency for higher incidence of emboligenic DWI lesions when using a shunt during CEA, compared to no shunting. Subgroup analysis for the asymptomatic carotid stenosis group shows a significant higher incidence of emboligenic DWI lesions when using a shunt. Most of the DWI lesions are clinically silent. The clinical relevance of cerebral embolization during CEA is under debate. Therefore, shunting during CEA must be carefully considered especially in asymptomatic patients.

ABSTRACT. Introduction: 3-10% of the population is suffering from PAD and 1-3% will develop CLI. One of the options to avoid major amputation and secure a better quality of life is an endovascular revascularization. The angiosome-concept divides the foot into six anatomic regions (angiosomes) fed by distinct source arteries arising from the posterior tibial, anterior tibial and peroneal arteries. This study investigates whether an endovascular procedure to the artery directly feeding the ischemic angiosome has an impact on wound healing, major amputation and mortality rate.

Materials/Methods: Retrospective analysis with prospective follow-up was performed at Ghent University Hospital of 131 non-healing ischemic wounds requiring endovascular revascularization in 109 patients. For every patient the site of the ulcer, the treated artery and the outcome were identified. The legs were divided into direct (DR) and indirect revascularization (IR).

Results: DR feeding the ulcer area was achieved in 88 legs (67%) compared with IR in 43 legs (33%). Revascularization was performed to the anterior tibial artery (49%), posterior tibial artery (26%) and peroneal artery (29%). There were no differences in comorbidities and wound characteristics except for ulcer localization and the treated vessel between the two groups. DR was not able to accomplish a higher healing rate, lower amputation rate or lower mortality rate compared to IR (p= .258, p= .828, p=.775). Wound infection (p= .038), high CRP (p= .007), renal insufficiency (p= .024) and a history of major amputation (p= 0.043) decreases wound healing rate. Patients who need a re-operation have a higher risk for minor amputation (p=.004).

Conclusion: Revascularization plays a crucial role in the treatment of ischemic lower extremity wounds. Similar results were obtained with regard to healing rates, limb salvage and mortality after DR compared to IR. Therefore revascularization should not be denied to patients in whom only indirect revascularization is possible.

ABSTRACT. Penetrating Atherosclerosis Aortic Ulcer : a re-appraisal

El Hassani I, Creemers E, Boesmans E, Van Damme H, Defraigne JO.

Dpt of Cardiovascular and Thoracic Surgery, University Hosiptal of Liège, Liège, Belgium

The authors observed the last two years (Sept. 2013-Sept. 2015) five cases of “Acute Aortic Syndrome” caused by a penetrating atherosclerotic ulcer of the descending thoracic aorta. This represents 10 % of all acute aortic syndromes admitted in the same period. All five patients benefitted thoracic endovascular stentgrafting with a 100% procedural success rate.

A literature review aims to define the distinct disease entity of penetrating aortic ulcer. It is opposed to intramural hematoma and acute aortic dissection, two more common pathologies manifesting as acute aortic syndrome. Natural history and optimal management of penetrating aortic ulcer are outlined according most recent insights.

ABSTRACT. OBJECTIVE Severe aortoiliac disease is often seen in patients with chronic renal insufficiency. This may compromise the possibility of a kidney transplantation. Exclusion from transplantation of these patients is common as early registry data suggested poor outcome. The aim of this study is to report our experience.

METHODS A retrospective review of all patients (n=15) undergoing an open surgical aortoiliac procedure to enable a kidney transplantation or to preserve the transplanted kidney between 1990 and 2015 was performed. Data collected included: patient demographics, comorbidities, renal pathology, duration of dialysis, vascular pathology, details of surgery, length of stay, perioperative complications, timing of kidney transplantation and overall survival.

RESULTS Aortoiliac reconstruction was performed successfully in all 15 patients. In 2 patients a simultaneous nephrectomy was performed. No intra-operative complications occurred. There were 7 postoperative complications: pulmonary infection (n=2), wound infection (n=2), wound dehiscence (n=1) and hypervolemia (n=2). The median length of stay was 9 days (range 7-46 days). The aortoiliac vascular pathology distribution as well as the outcome are summarized in figure 1. The kidney transplantation was eventually performed in 7 patients: simultaneously (n=1), metachronously within 2 months (n=1) or distant with the aortic surgery, between 7 and 21 months (n=5). Median overall survival after aortic surgery was 4 years (range 1-16 years).

CONCLUSION Chronic renal failure is often associated with severe aortoiliac disease. In some cases this may compromise the possibility of a kidney transplantation. Literature suggests that kidney transplantation offers the best chance of survival and improves health-related quality of life compared to permanent dialysis. On the other hand, life expectancy in this population is seriously impaired due to severe cardiovascular comorbidity. Death with a functioning graft is a common cause of graft loss. This should be taken into account when considering vascular reconstruction to enable kidney transplantation.

ABSTRACT. Objective Groin infections adjacent to vascular groin surgery continue to be a challenge. Research suggests that anti-microbial therapy and debridement in conjunction with muscle flaps can be effective in managing these wounds with preservation of graft and extremity. Several muscle flaps can be used, of which the sartorius and rectus femoris are best described. Even though the satorius is commonly used in the Netherlands, literature suggests better short- and long-term results for the rectus flap. We aimed to describe our experience with the rectus femoris flap in management of groin infections.

Methods Eighteen consecutive rectus femoris muscle flaps, performed between 2008-2015 in 16 patients with localized groin infections, were retrospectively reviewed. In addition two patients who received three flaps because of prophylactic measures were included.

Results Eighteen patients (mean age 70.1) were followed up for 13.5 months. All were treated with a rectus femoris flap (n= 21).There was no intra-operative mortality. Seventeen wounds healed, 14 primarily. Three patients had ongoing infection after flap treatment, three experienced re-infection. Three patients had uncomplicated secondary healing: one after antibiotics, two required VAC-therapy. Four patients died during hospitalization. One due to cardiac complications postoperatively, three due to vascular complications. Two died after anastomotic haemorrhage due to on-going infection. The other experienced re-infection with full necrosis of the flap and chose euthanasia as there were no further therapeutic options. Six more patients died during follow-up of non-related problems.

Conclusions In our experience, the rectus femoris muscle flap is an effective and reliable technique and is the flap of choice for complex groin wound reconstruction. In the majority of cases, wounds might heal primarily with this approach and rejection or necrosis of the flap is uncommon. Randomised controlled trials still need to be conducted to provide de necessary proof of the superiority of the rectus femoris over the sartorius flap.

ABSTRACT. Objective To analyze section margins using the Leeds Pathology Protocol (LEEPP) (Verbeke C et al. BJS 2006) after pancreaticoduodenectomy for malignant peri-ampullary tumors.

Methods All resection specimens of consecutive patients undergoing hemipancraticoduodenectomy or total pancretectomy since 09/2013 were analyzed. Patients undergoing pancreatic resection for intraductal papillary mucinous neoplasms, neuro-endocrine tumors, solid papillary epithelial neoplasm and chronic pancreatitis were excluded from the analysis. All hemipancreaticoduodenectomy and total pancratectomy resection specimens since 09/2013 were managed following a standard operating procedure using the LEEPP. Anterior (blue), posterior including SMA margin (black), portal vein/SMV groove (green), pancreatic transection (red) margins were inked separtely. All specimens were sectioned in the axial plane. Positive section margins were defined when the minimal distance to the inked margin was <1mm.

Results Thirty-five resection specimens for malignant peri-ampullary tumors were retained for analysis. Positive sections margins were found in 5 (14%) and 13 (37%) of resection specimens depending on a definition of margin positivity of 0mm or <1mm respectively. Anterior, posterior, superior mesenteric vein and pancreatic transection margins were involved in 2 (6%), 3 (9%), 9 (26%) and 0 (0%) of specimens respectively. Median time to recurrence (months) was significantly shorter for patients with positive vs. negative sections margins with 3.2 vs. 9.8 months respectively (p=0.01, Wilcoxon).

Conclusions When using the LEEPP section margins are a common finding after resection of malignant peri-ampullary tumors. Correct benchmarking of section margin positivity after pancreatic resection is possible only after standardization of pathology protocols.

ABSTRACT. Objective: The Open New Simplified Totally Extra-Peritoneal (ONSTEP) inguinal hernia repair is a recently described technique which involves placing a pre-shaped mesh partly in the preperitoneal space and partly between the internal and external oblique muscles. Assumed advantages are a shorter duration of surgery, the possibility to perform the procedure under local anesthesia, short recovery time and rapid return to daily activities, low incidence of chronic post-operative groin pain, low recurrence rate and a short hospital stay. This study presents our initial experience with this novel technique. Methods : We constructed a prospective database of all patients with an inguinal hernia who underwent a hernia repair with the ONSTEP technique using a Polysoft® hernia mesh. During a 2.5-year period one hundred and twenty-five patients underwent an inguinal hernia repair with this novel technique. One experienced attending surgeon performed all procedures. Systematic follow-up at 6 weeks postoperative was performed. Patients were followed for pain complaints, wound problems and recurrence. We compared our preliminary results with recent scientific literature. Results : No perioperative complications occurred. Mean operating time was 29.8 minutes. No postoperative wound infections occurred. We encountered 1 local recurrence (0,8%). Four patients experienced inguinal pain (3.2%) and seven patients experienced testicular pain (5.6%) six weeks postoperatively. Four patients developed a minor hematoma (3.2%). No patients had any limitations in daily activity. Conclusions : In our experience, the ONSTEP technique is a feasible method for inguinal hernia repair. This technique tends to produce consistent results and is associated with very low overall complication rates, chronic pain and recurrence rates with a short learning curve. Long-term results as well as randomized studies should be awaited to make conclusions comparing current accepted techniques.

ABSTRACT. OBJECTIVE: To investigate the effect of the inclusion of a liver graft on outcome after intestinal transplantation. METHODS: A retrospective analysis was performed on our database of intestinal transplant recipients, containing recipients of either liver free grafts (LFG) or liver containing grafts (LCG). The data was analyzed on the basis of clinical outcomes, rejection, and survival. We only included patients who received a cadaveric graft. RESULTS: From 2000 onwards, 15 patients with irreversible intestinal failure received an intestinal transplantation at our center. Of these, 9 received a LCG and 6 a LFG. 3 were pediatric patients. All received their grafts from brain dead donors that had a negative cross-match. HLA matching was at random. 12 patients (80%) are alive and 11 of these are TPN-independent at home. 1 patient lost her intestinal graft after an endoscopy. There were 3 patient deaths: 2 in LCG recipients (1 to invasive aspergillosis and 1 to NSAID related ulcerations) and 1 in LFG recipient (invasive aspergillosis). The 5 year patient survival for LCG and LFG was 88.8% and 83.3% respectively. 5 year graft survival was 88.8% in LCG and 62.3% in LFG. 33% of LCG patients experienced acute rejection versus 50% of LFG patients. Of the latter, 2 patients experienced recurrent acute rejections episodes. No chronic rejections were observed. All rejections could be treated by increasing immunosuppression. No grafts were lost due to rejection or infection. No donor specific antibodies were detected in any patients. CONCLUSIONS: Inclusion of the liver in an intestinal transplantation did not lead to poorer results. On the contrary, there was a trend for less rejection and better graft survival when the liver was co-transplanted. Both liver containing- and liver free intestinal transplantations represent lifesaving procedures with excellent outcomes.

ABSTRACT. Objective A quality parameter after pancreatic surgery might be the receipt of adjuvant therapy post-surgery. The aim of this study was to evaluate postoperative complications in relation to receipt of adjuvant chemotherapy and survival in patients treated for pancreatic cancer in a tertiary referral hospital.

Methods All consecutive pancreatic adenocarcinoma patients (2009-2015) undergoing surgical resection were included. Receipt of adjuvant therapy was compared between patients with and without postoperative complications according to Clavien Dindo classification, age and marital status.

Results 153 patients were identified (median age 66 years), of which 42.5% had at least 1 postoperative complication. Only 3% of the patients with complications had Clavien Dindo IV. 6.5% of all patients needed surgical or radiological intervention due to a pancreatic fistula, chyle leakage, collections or abscess formation. Omission of adjuvant therapy is more frequent in patients with complications (21.7% vs. 9.9%; p=0.039). Other factors significantly associated with omission were age > 65 and single status. 2-year survival is significantly improved for patients who received adjuvant therapy versus no therapy (51.9% vs. 25.0%; p=0.049). The presence of postoperative complications versus none did not affect long-term survival (45.0% vs 41.4%, 2009-2013, with follow-up trough 2015). Patients’ own choice to refuse adjuvant therapy was the main reason for omission (38.8%). Medical reasons for omission counted for 22%.

Conclusions Although standardized surgical techniques and postoperative management lead to low 30-day morbidity and mortality in our series, patients’ own choice, higher age and single status seem to be the most frequent reasons for omission of adjuvant therapy. It is important to identify these subgroups to achieve best outcomes in terms of survival.

ABSTRACT. We present a case of acute and nodular radiation hepatitis of the left liver after neo-adjuvant chemoradiotherapy for distal esophageal cancer, which resembles a hepatic metastasis on PET/CT. Acute and nodular radiation hepatitis can be a potential cause of false-positive findings of malignancy and therefore exclude patients who could benefit from esophagectomy. PET/CT images should therefore carefully be interpreted and compared with the radiation beams, dose distribution and eventually clarified by MR imaging.

ABSTRACT. Objective: To assess the use of mesentericoportal (meso-Rex) shunt in the management of portal hypertension due to extra-hepatic portal thrombosis in adult population

Background: Extra-hepatic portal thrombosis is not unusual in patient with chronic pancreatitis or following pancreatic surgery with venous reconstruction. In some patients the resulting portal hypertension may lead to severe bleeding refractory to endoscopic or interventional radiology approach. The Meso-Res bypass, a surgical shunt that has the advantage of preserving the hepatopedal blood flow, has been used successfully in children with extrahepatic portal vein obstruction. We describe our experience with this shunt in adults.

Methods: Clinical data in 4 patients with extrahepatic vein thrombosis, 2 following duodenopancreatectomy and 2 with chronic pancreatitis were analyzed. Preoperatively, all patients underwent liver biopsy, percutaneous portal angiography and triphasic abdominal CT scanner.

Results: Meso-Rex bypass was done in all 4 patients. Mixed synthetic and autologous venous graft was used in three patients and classical autologous internal jugular vein in one. There was no death or major morbidity, and gastrointestinal (GI) bleeding was controlled in all patients.

Conclusions: Meso-rex shunt represent a safe and effective technique to treat refractory GI bleeding secondary to extra-hepatic portal hypertension in adult population.

ABSTRACT. Objective: To assess simple layer peritoneal constructed tube as an autogenous substitute for inferior vena cava replacement.

Background: Extensive en-bloc multivisceral resection with major vessels has proven to be effective in selected abdominal malignancies. The need of vascular reconstruction represents a surgical challenge. We described the use of the peritoneum alone as a homologous graft.

Methods: Autogenous parietal peritoneum without fascia was harvested and tubulized to replace vena cava in selected patients with complex abdominal tumors. We collected retrospectively preoperative and intraoperative data. We evaluated surgical morbidity with Clavien-Dindo classification and early results as graft patency, tumor recurrence and performance scale (Karnofsky).

Results: 4 patients had multiorgan resections for malignancies involving retro-hepatic vena cava. All patients had replacement of infrarenal and suprarenal inferior vena cava . Major hepatectomy was performed in 2 patients. One patient has needed veno-venous bypass. Right nephrectomy was done in all patients. R0 resection was achieved in all patients. There was no morbidity excepted for one patient (Clavien Dindo IIIb). Four-month graft patency was confirmed with ultra-sound and CT scan with no sign of disease recurrence. Mean Karnosfky performances scale was 90% 4 months after surgery.

Conclusions: Autogenous non fascial parietal peritoneum is a safe and effective option for circumferential replacement of IVC after extensive en-bloc tumor resection with vena cava involvement.

ABSTRACT. INTRODUCTION Treatment of aortic arch hypoplasia is an important surgical challenge. The diversity of the surgical techniques described in the literature and the disparity of patient’s characteristics make the choice of the surgical strategy widely open. The technique performed at H.U.D.E.R.F. since multiple years is an enlargement of the aortic arch using a pericardial autologous patch treated in a glutaraldehyde solution. METHODS Retrospective analysis of surgical results with long-term follow-up of aortic arch reconstruction using pericardial patch in 38 newborns. Neonates were divided in two groups: hypoplasia associated with simple heart defects (groupe 1), and hypoplasia associated with severe heart defects (groupe 2). RESULTS Postoperative mortality in group 1 and 2 are respectively 9% and 25%. Intubation time and intensive care unit stay were significantly different between the 2 populations. Major complications were pulmonary hypertension associated with hemodynamic instability. No aneurysmal dilatation was detected. Two early restenosis were treated with endoluminal percutaneous angioplasty. Freedom from restenosis intervals for both groups postoperatively were 96.6% at 3 months and 93.3% at 4 months. CONCLUSIONS The use of pericardial autologous patch treated with glutaraldehyde is an effective technique compared to other surgical alternatives. There were no aneurismal dilatation and a poor incidence of restenosis. Its growth potential and non-immunogenic characteristic make it an optimal patch for newborn population.

ABSTRACT. OBJECTIVE : To report a case of bilateral renal autotransplantation in a Loin Pain Haematuria Syndrome (LPHS).

METHODS : We report a case of a 29-year-old female with bilateral severe loin pain associated with frequent macroscopic haematuria and with major restriction in her daily life activities. Diagnosis of LPHS wa made by exclusion. She required large doses of painkillers, including oxycodone, tramadol and trazolan. A right renal autotransplantation was first performed in March 2015 leading to a complete disappearance of the pain on the right side. Owing to this good result,a second autotransplantation was made on the left side.

RESULTS : The patient was discharged on post-operative day four with complete relief of pain. She is currently doing well and has resumed her studies.

CONCLUSIONS : In our experience, renal autotransplantation is a good indication for LPHS. The procedure allows the patient to restart a normal life and to be free from drug dependence. This is the second case of LPHS treated by renal autotransplantation in our centre. We believe that kidney autotransplantation is a safe and definitive cure for LPHS.

ABSTRACT. OBJECTIVE: Video assisted thoracoscopic surgery (VATS) is an accepted minimal invasive approach in lung surgery. There is a reduced respiratory complication rate but tactile feedback is lost in comparison to thoracotomy. Limited evidence suggests favorable short-term outcomes in VATS segmentectomy compared to limited thoracotomy segmentectomy. There is debate whether VATS is feasible for metastasectomy. Some prefer a limited thoracotomy or a transxiphoidal approach to manually locate the nodule, limit lung resection and inspect for occult metastases. Currently, there is lack of evidence regarding the influence of non-resected metastases on survival. METHODS: We report a case where CT-guided vascular coil placement and peroperative fluoroscopy were used to perform a VATS apical anatomical segmentectomy. RESULTS: We report the case of a 56 years old female with a pT4aN0M1b stade IV melanoma originating from a congenital naevus at the right leg. PET-CT had shown a solitary lung nodule of 14mm, histological proven to be a melanoma metastasis. After 9 months therapy with pembrolizumab, disease was stable without appearance of new metastasis or growth nor regression of the known lung nodule. The decision was made to resect the nodule. Since the nodule was centrally located in the right upper lobe, CT-guided vascular coil placement into the nodule was used. A VATS apical anatomical segmentectomy was performed. Peroperative fluoroscopy confirmed the location of the nodule before the stapler on lung parenchyma was fired. A complete resection of the nodule, with free resection margins was performed using VATS without palpation or direct visualization of the nodule and without the need for lobectomy or limited thoracotomy. CONCLUSIONS: In case of metastasectomy in the lung, CT-guided coil placement into the nodule can be used to locate an expected peroperative invisible nodule. An anatomical apical segmentectomy can be performed using VATS in selected patients in a safe way.

ABSTRACT. Aims: To achieve additional weight loss or to resolve band-related problems, a laparoscopic adjustable gastric banding (LAGB) can be converted to a laparoscopic Roux-en-Y gastric bypass (RYGB). There is limited data on the feasibility and safety of routinely performing a single-step conversion. We assessed the efficacy of this revisional approach in a large cohort of patients operated in an ultra-high volume bariatric institution. Methods: Between October 2004 and December 2015, a total of 885 patients who underwent LAGB removal with RYGB were identified from a prospectively collated database. In all cases a single stage conversion procedure was planned. The feasibility of this approach and peri-operative outcomes of these patients were evaluated and analyzed. Results: A single-step procedure was successfully achieved in 738 (83.4 %) of the 885 patients. During the study period, there was a significant increase in performing a single stage conversion from LAGB to RYGB, with 94.7 % of patients undergoing a single (as opposed to a two) staged procedure in the last 5 years of the study and no impact on the complication rate. No mortality or anastomotic leakage was observed in both groups. Only 45 patients (5.1 %) had a 30-day complication: most commonly haemorrhage (N=20/45). Conclusion: Converting a LAGB to RYGB can be performed with a very low morbidity and zero-mortality in a high-volume revisional bariatric center. With increasing experience, and full standardization of the conversion, the vast majority of operations can be performed as a single-stage procedure without an influence on the complication rate, and outcomes similar to primary RYGB.

ABSTRACT. Objective Tumor regression grading (TRG) systems categorize the amount of residual tumor volume on the primary tumor in a resection specimen after neoadjuvant treatment. Aim of this study was to evaluate the impact of Mandard TRG, residual tumor depth (ypT) and residual lymph node status (ypN) and characteristics i.e. intracapsular versus extracapsular involvement on overall (OS) and disease-free survival (DFS) in adenocarcinoma (ADC) and squamous cell carcinoma (SCC) of the esophagus. Methods Between 2005 and 2014, 344 patients who received R0-esophagectomy after neoadjuvant chemoradiation therapy from a prospectively maintained databasewere selected. Mandard TRG, ypTNM and lymph node characteristics were prospectively recorded. OS and DFS were calculated by means of Kaplan-Meier curves and compared by Cox regression analysis. Results Mandard TRG grade 1 (complete regression) was found in 110 (32%); grade 2 (fibrosis with scattered tumor cells) in 120 (35%); grade 3 (tumor cells with preponderance of fibrosis) in 53 (15%); grade 4 (fibrosis and tumor cells with preponderance of tumor cells) in 54 (16%) and grade 5 (tumor tissue without signs of regression) in 7 (2%) patients. Both OS and DFS showed no significant difference between grade 1 and 2 (p=0.059 and 0.105 respectively). Therefore grades 1/2 were classified together as ‘major response’, grades 3/4 as ‘minor response’ and grade 5 as ‘no response’. Multivariate analysis showed two independent prognosticators for OS (TRG-response and number of positive lymph nodes) and three independent prognosticators for DFS (TRG-response, ypT and lymphnode-characteristics). Conclusion After neoadjuvant chemoradiation followed by surgery for esophageal carcinoma, number of residual positive lymphnodes as well as TRG-response are strong prognosticators for OS. Minor TRG-response, but also depth of residual tumor (ypT) and extracapsular lymphnode invasion are negative prognosticators for recurrence.These parameters might facilitate postoperative tumor board discussions regarding risk analysis of specific patients and adjuvant therapies.

ABSTRACT. Objective Intestinal ischemia is a highly-lethal clinical condition. The farnesoid X receptor (FXR) is abundantly expressed in the ileum, where it acts as a regulator of intestinal innate immunity and homeostasis. The aim of our study was to investigate, for the first time, if the FXR-agonist obeticholic acid (OCA/INT-747) could attenuate intestinal ischemia reperfusion injury (IRI) in a rat model.

Methods In a rat model of intestinal IRI (laparotomy + temporary mesenteric artery clamping), 3 conditions were tested (n=16/group): laparotomy only (sham group); ischemia 60min + reperfusion 60min + vehicle pretreatment (IR group); ischemia 60min + reperfusion 60min + OCA pretreatment (IR+OCA group). Vehicle or OCA (INT-747, 2*30mg/kg) was administered by gavage 24h and 4h prior to IRI. The following end-points were analyzed: 7-day survival; biomarkers of enterocyte viability (L-lactate, I-FABP); histology (morphologic injury to villi/crypts {Park-Chiu score} and villus length); intestinal permeability (Ussing chamber); endotoxin translocation (Lipopolysaccharide assay); inflammatory cytokines (IL-6, IL-1-β, TNFα, IFN-γ IL-10, IL-13); apoptosis (cleaved caspase-3); and autophagy (LC3, p62) (ELISA, Western-Blot, qPCR).

Results IRI was associated with high mortality (90%); loss of intestinal integrity (structurally and functionally); increased endotoxin translocation and pro-inflammatory cytokine production; and inhibition of autophagy. Conversely, OCA-pretreatment improved 7-day survival up to 50% (Fig 1A) which was associated with prevention of epithelial injury, preserved intestinal architecture (Fig 1B) and permeability. Additionally, FXR-agonism led to decreased pro-inflammatory cytokine release and alleviated autophagy inhibition.

Conclusions For the first time we showed that pretreatment with OCA, an FXR-agonist, improves survival in a rodent model of intestinal IRI, preserves the gut barrier function and suppresses inflammation. These results turn FXR into a promising target for various conditions associated with intestinal ischemia.

ABSTRACT. Objective Long-segment tracheal pathologies are associated with high morbidity and mortality. Despite a relatively straightforward anatomy of the trachea, reconstruction might be deceptive. Key elements of successful transplantation include the use of biocompatible constructs with little immune-reactivity, vascularization of the submucosal lining and creation of an epithelial covering. From our clinical and experimental work on allotrachea transplantation, we witnessed that allogenic chondrocytes might be protected from an overt immune response due to physical isolation within a dense collagenous matrix, i.e. by immunological ignorance. Our aim was to evaluate the in-vivo response of rabbit allotrachea, stripped of its highly-immunogenic inner lining. Secondly, we established whether this construct might serve as a suitable scaffold for autologous epithelial grafting.

Methods Mucosa and submucosa of twelve rabbit tracheae were mechanically peeled off. Allogenic cartilage was covered with Integra®. Constructs were implanted within the rabbit’s lateral thoracic artery flap. After revascularization, the Integra®-covering of six allotracheae was grafted with autologous buccal mucosa. Macroscopical, histological analysis and immunohistochemistry were performed on explants at termination.

Results Revascularization and buccal grafting was incomplete in two circular constructs. The following ten transplants were opened longitudinally before implantation. Integra® revascularized well. One trachea showed complete graft-adherence. Three tracheae showed satisfactory covering, though migrating epithelium tended to grow invasively within the Integra®-scaffold. Moderate lymphocytic infiltration surrounding exposed allogenic chondrocytes was consistently visualized.

Conclusions Mechanically-stripped allogenic tracheae exhibited beneficial in-vivo properties. By opening tracheae, insufficient revascularization through intercartilaginous ligaments could be overcome successfully. Integra® proved to be a suitable scaffold for cartilage covering. However, cartilage-trauma due to stripping revealed the immunogenic potential of chondrocytes. Additionally, absence of a specialized basement membrane, providing efficient guidance of epithelium, will likely limit success of future respiratory-cell seeding. Therefore, we currently focus on gentle detergent-enzymatic decellularization techniques, with preservation of basement membrane and submucosal scaffold to guide reepithelialization and revascularization.