WITHDRAWN: A single center experience in resectable pancreatic ductal adenocarcinoma : the limitations of the surgery-first approach. Critical review of the literature and proposals for practice update.

The article has been withdrawn at the request of the authors and editor because of incorrect authorship, which is considered a form of unethical publication. The Publisher apologizes for any inconvenience this may cause.

A single center experience in resectable pancreatic ductal adenocarcinoma : the limitations of the surgery-first approach. Critical review of the literature and proposals for practice update.

BACKGROUND AND STUDY AIMS: The current standard of care for resectable pancreatic ductal adenocarcinoma (PDAC) is surgery-first followed by adjuvant chemotherapy. We review our single center experience in a PDAC cohort managed by the surgery-first strategy. We then compare our data to those of Belgian and international literature. PATIENTS METHODS: We reviewed a series of 83 consecutive resectable patients with PDAC, treated by the surgery-first approach in a Belgian Academic Hospital between 2007 and 2013. The outcomes were assessed with univariate and multivariate Cox regression analysis. Kaplan-Meier curves were drawn according to patient groups. RESULTS: For the entire population, the median survival (MS) was 18.4 months; the 1-year relapse-free survival was 56%, and the 5-year overall survival (OS) was 13%. The size of the primary tumor larger than 3 cm (OS, HR = 1.76, p = 0.033) and vascular resection (DFS, HR = 2.1, p = 0.024) were the single independent prognostic factors in the multivariate analysis of this cohort. Only 69% of the patients received adjuvant chemotherapy, and more than 75% of them demonstrated no chance of survival beyond 3 years because they harbored poor prognostic factors, recognized only postoperatively. CONCLUSIONS: Our results and those published in the literature brought to light the limited perspectives of the surgery-first strategy in a population of apparently resectable pancreatic cancers. In comparison, data from reported neo-adjuvant series deserve our interest to bring this strategy upfront in selected patients in the context of close observational monitoring and randomized trials. The actual standard of care for resectable PDAC is surgery-first followed by adjuvant chemotherapy. The performance of this strategy relies on the dedicated imaging that does not accurately recognize the limits of the tumor and the high prevalence of adverse prognostic factors. Moreover, pancreatectomy remains associated with high postoperative complication rates and the poor completion of adjuvant therapy. This translates into poor long-term survival figures. In our series the MS was 18.4 months and 5-year OS was 13%. The disease-free survival (DFS) was 15.6 months, 1 and 3-year DFS were 56 and 26%, respectively. The variables that significantly correlated with OS in univariate analysis are tumor size and lymph node involvement. Regarding DFS, vascular resection was the only significant factor. In the multivariate analysis, the only significant factor related to OS remained the tumor size >3 cm in greatest diameter. Vascular resection remained significant for DFS. 31% of the patients did not receive any chemotherapy at all before the 6-month period following resection. The rates of complete resections compared favorably with those of a surgery-first strategy with no excess of operative mortality, complications and early relapse rates. The advantages of a chemotherapy-first approach, eventually combined with chemo-radiotherapy, are to offer higher combined therapy completion rates and improve the level of free resection margins, lymph node involvement and patient selection. The advent of safe, more potent chemotherapy combinations has the potential to further improve survival when administered upfront.

Recruitment of lung volume during surgery neither affects the postoperative spirometry nor the risk of hypoxaemia after laparoscopic gastric bypass in morbidly obese patients: a randomized controlled study.

BACKGROUND: Intraoperative recruitment manoeuvres (RMs) combined with PEEP reverse the decrease in functional residual capacity (FRC) associated with anaesthesia and improve intraoperative oxygenation. Whether these benefits persist after operation remains unknown. We tested the hypothesis that intraoperative RMs associated with PEEP improve postoperative spirometry including FRC and reduce the incidence of postoperative hypoxaemia in morbidly obese (MO) patients undergoing laparoscopic gastric bypass. METHODS: After IRB approval and informed consent, 50 MO patients undergoing laparoscopic gastric bypass under volume-controlled ventilation (tidal volume 6 ml kg(-1) of IBW) were randomly ventilated with either 10 cm H2O PEEP or with 10 cm H2O PEEP and one RM carried out after induction of pneumoperitoneum, and another after exsufflation. Anaesthesia and analgesia were standardized. Spirometry was assessed before operation and 24 h after surgery. Postoperative oxygenation and the apnoea-hypopnoea index (AHI) were recorded during the first postoperative night. RESULTS: Age, BMI, and STOP BANG score were similar in both groups. FRC decrease after surgery was minimal [0.15 (0.14) litre in control and 0.38 (0.19) litre in the RM group] and similar between the groups (P=0.35). FVC, FEV1, mean [Formula: see text], percentage of time spent with [Formula: see text] below 90%, and AHI did not differ significantly between the groups. CONCLUSIONS: This study demonstrates that when added to a protective mechanical ventilation combining low tidal volume and high PEEP, two RMs do not improve postoperative lung function including FRC, arterial oxygenation, and the incidence of obstructive apnoea in MO patients after laparoscopic upper abdominal surgery. CLINICAL TRIAL REGISTRATION: EudraCT 2011-000999-33.

Donor age as a risk factor in donation after circulatory death liver transplantation in a controlled withdrawal protocol programme.

BACKGROUND: Results of donation after circulatory death (DCD) liver transplantation are impaired by graft loss, resulting mainly from non-anastomotic biliary stricture. Donor age is a risk factor in deceased donor liver transplantation, and particularly in DCD liver transplantation. At the authors' institute, age is not an absolute exclusion criterion for discarding DCD liver grafts, DCD donors receive comfort therapy before withdrawal, and cold ischaemia is minimized. METHODS: All consecutive DCD liver transplantations performed from 2003 to 2012 were studied retrospectively. Three age groups were compared in terms of donor and recipient demographics, procurement and transplantation conditions, peak laboratory values during the first post-transplant 72 h, and results at 1 and 3 years. RESULTS: A total of 70 DCD liver transplants were performed, including 32 liver grafts from donors aged 55 years or less, 20 aged 56-69 years, and 18 aged 70 years or more. The overall graft survival rate at 1 month, 1 and 3 years was 99, 91 and 72 per cent respectively, with no graft lost secondary to non-anastomotic stricture. No difference other than age was noted between the three groups for donor or recipient characteristics, or procurement conditions. No primary non-function occurred, but one patient needed retransplantation for artery thrombosis. Biliary complications were similar in the three groups. Graft and patient survival rates were no different at 1 and 3 years between the three groups (P = 0.605). CONCLUSION: Results for DCD liver transplantation from younger and older donors were similar. Donor age above 50 years should not be a contraindication to DCD liver transplantation if other donor risk factors (such as warm and cold ischaemia time) are minimized.

Evolution of native kidney function after pancreas transplantation alone.

INTRODUCTION: This study investigated changes in kidney function over time among a cohort of patients undergoing pancreas transplantation alone (PTA) from January 2002 to December 2011. PATIENTS AND METHODS: Ten of eighteen PTA patients bearing functioning grafts for at least 1 year were recruited for the analysis. Primary endpoints were changes in mean serum creatinine (SCr, mg/L) and mean estimated glomerular filtration rate (eGFR) using the 4-variable Levey-MDRD equation (mL/min/1.73 m(2)) comparing baseline (pretransplantation) to 6-month, 1-year, 3-year, and 5-year posttransplantation values. Mean follow-up time was 75.7 ± 20.5 months (range, 46-106.5). RESULTS: Baseline eGFR was 89.3 ± 27.9 (range, 58-145). eGFR decreased to 75.7 ± 26.2, 71 ± 20.6, 66.5 ± 14.8, and 62.1 ± 11.2 at 6 months, 1, 3, and 5 years representing -15.2%, -20.5%, -15.8%, and -22.6% percentage decreases respectively (P < .05 for all pairwise comparisons). The Baseline SCr was 8.6 ± 2.3 mg/L (range, 5-13). SCr progressively increased to 10.1 ± 3, 10.5 ± 3.1, 10.9 ± 3.1, and 11.3 ± 1.7 at 6 months, 1, 3, and 5 years a 17.1%, 22%, 16.6%, and 19.9% increase respectively (P < .05 for all pairwise comparisons). One of ten, 2/8, and 3/7 patients displayed an eGFR <60 at transplantation versus 3 and 5 years thereafter, respectively. No patient developed a SCr > 25 mg/L or eGFR <30 or needed dialysis or kidney transplantation. Five of ten patients had micro-albuminuria or proteinuria before transplantation. Tacrolimus levels were within recommended therapeutic ranges over time. CONCLUSION: Kidney function deteriorated significantly after PTA. Understanding of risk factors for the development of renal impairment is important to preserve kidney function and to select appropriate candidates for PTA.

End of life care in the operating room for non-heart-beating donors: organization at the University Hospital of Liège.

Non-heart-beating (NHB) organ donation has become an alternative source to increase organ supply for transplantation. A NHB donation program was implemented in our institution in 2002. As in many institutions the end of life care of the NHB donor (NHBD) is terminated in the operating room (OR) to reduce warm ischemia time. Herein we have described the organization of end of life care for these patients in our institution, including the problems addressed, the solution proposed, and the remaining issues. Emphasis is given to our protocol elaborated with the different contributors of the chain of the NHB donation program. This protocol specifies the information mandatory in the medical records, the end of life care procedure, the determination of death, and the issue of organ preservation measures before NHBD death. The persisting malaise associated with NHB donation reported by OR nurses is finally documented using an anonymous questionnaire.

Contribution of donors after cardiac death to the deceased donor pool: 2002 to 2009 University of Liege experience.

OBJECTIVE: In this study, we have evaluated the organ procurement and transplantation activity from donors after cardiac death (DCD) at our institution over an 8-year period. Our aim was to determine whether this program influenced transplantation programs, or donation after brain death (DBD) activity. METHODS: We prospectively collected our procurement and transplantation statistics in a database for retrospective review. RESULTS: We observed an increasing trend in potential and actual DCD number. The mean conversion rate turning potential into effective donors was 58.1%. DCD accounted for 16.6% of the deceased donor (DD) pool over 8 years. The mean age for effective DCD donors was 53.9 years (range, 3-79). Among the effective donors, 63.3% (n = 31) came from the transplant center and 36.7% (n = 18) were referred from collaborative hospitals. All donors were Maastricht III category. The number of kidney and liver transplants using DCD sources tended to increase. DCD kidney transplants represented 10.8% of the DD kidney pool and DCD liver transplants made up 13.9% of the DD liver pool over 8 years. The DBD program activity increased in the same time period. In 2009, 17 DCD and 33 DBD procurements were performed in a region with a little >1 million inhabitants. CONCLUSION: The establishment of a DCD program in our institution enlarged the donor pool and did not compromise the development of the DBD program. In our experience, DCD are a valuable source for abdominal organ transplantation.

[When should we resect colorectal liver metastases?]. / Quand doit-on réséquer les métastases hépatiques d'un cancer colorectal?

6000 new cases of colorectal cancer are diagnosed each year in Belgium. 50% of these patients shall develop liver metastasis. Resection remains the only chance of long term survival and must be considered as an endpoint from the beginning of the treatment. It is the result of a multidisciplinary discussion and a global approach of the disease. It is rarely directly feasible, but there are many techniques which may make it achievable in the end. Today, resection criteria are exclusively technical and neither bad prognosis factors, nor the presence of extra-hepatic metastases should exclude liver resection. This resection must be assessed by a confirmed hepatobiliary surgeon and must be proposed to all patients whatever their age as long as their general state of health is good.

Avoiding blood products during liver transplantation.

Liver transplantation is a major surgical procedure usually requiring large amount of blood products (red cells, platelets, fresh-frozen plasma). We developed a multidisciplinary transfusion-free protocol for liver transplantation in Jehovah's witnesses who refuse the use of blood products but accept organ transplantation. Between September 1998 and November 2004, 9 of 29 Jehovah's witnesses evaluated for liver transplantation were transplanted after medical preparation. None of these patients received any blood product during the surgical procedure. This experience may be beneficial for the entire liver transplantation population, as excessive transfusion has been linked to increased morbidity and mortality in liver transplantation.

A new model for human intestinal preservation: comparison of University of Wisconsin and Celsior preservation solutions.

AIM: We compared University of Wisconsin (UW) and Celsior preservation solutions using a new model of human intestinal preservation that mimics the clinical conditions of small bowel procurement. METHODS: Intestinal grafts were harvested from four multiorgan donors. After classic warm dissection for organ procurement, an ileal segment of 50 cm was immediately flushed with Celsior. After the perfusion of the abdominal organs with UW, a second segment of adjacent ileum was harvested. The two intestinal grafts were then divided into segments by stapling, before immersion into the corresponding preservation solution (Celsior or UW) for 0-, 6-, 12-, or 24-hour incubation at 4 degrees C. A histological score was graded after blinded examination of three random specimens within each ileal graft for each duration of preservation. RESULTS: Control specimens showed normal histology. After 6 hours of preservation, most villi showed complete epithelial detachment although the crypts appeared intact. After 12 hours of preservation, a larger proportion of the villi showed extensive epithelial sloughing. After 24 hours, the damage involved the entire mucosa with the crypt epithelium largely detached from the basal membrane. No statistical difference in histological score was observed between the two preservation solutions. CONCLUSION: This study showed severe histological alterations of graft mucosa after short periods of preservation by UW or Celsior solutions. This model may be useful to evaluate improvements in the quality of preservation of human intestinal transplants.

Luminal contact with University of Wisconsin solution improves human small bowel preservation.

AIM: Under clinical conditions small bowel mucosa is stored without any contact between the mucosa and the preservation solution. We evaluated the impact of luminal contact with University of Wisconsin solution (UW) on the structural quality of small bowel preservation. METHODS: Segments of ileum harvested from stable multi-organ donors were flushed with UW. For each donor, ileal segments were placed in UW without any contact between the mucosa and the preservation solution (group A), as is practiced in clinical conditions. Adjacent segments were cut on their antimesenteric side and placed in UW so that their mucosa was widely in contact with the solution (group B). The grafts preserved in ice were removed from the preservation fluid at different times (0, 3, 6, or 12 hours). Tissues were studied by optical microscopy after H&E staining of formalin-fixed, paraffin-embedded specimens. A median histologic score was calculated after examination of three random slides for each ileal segment per time point. Comparisons were performed between tissues of groups A and B from the same donor. RESULTS: Control (0h) specimens showed normal histology. As early as 3 hours of preservation, group A tissues showed detachment of the villar epithelium. At 6 and 12 hours of preservation in this group further tissue alteration were obvious with complete epithelial detachment from the basal membrane of the villi. The histologic score of the segments preserved by luminal contact with UW was always significantly higher than the controls from the same donor. CONCLUSION: Luminal contact between the mucosa of intestinal grafts and UW improves the quality of human small bowel preservation.

Strictureplasty in Crohn's disease: short- and long-term follow-up.

Strictureplasty for obstructive Crohn's disease is still controversial because lesions are left in place and the suture is performed on a diseased bowel. Many surgeons prefer to perform bowel resection, hoping for fewer complications and a lower recurrence rate. In this paper, the authors reports their strictureplasty experience. They performed a systematic retrospective review of the patients suffering from Crohn's disease who underwent strictureplasties during a 10-year period in the abdominal surgery department of the University Hospital of Liège Sart Tilman, and studied the short- and long-term clinical results of 68 strictureplasties performed in 18 patients. Median follow-up was 63 months (range 12 to 144). Mortality was 0% and septic morbidity was 11% (one wound abscess and one leakage). Among the 16 patients available for the latest follow-up, symptomatic stenotic recurrence had to be medically treated in hospital for 4 patients (25%) with a recurrence delay range of 19 to 49 months. Stenosis recurrence needed re-intervention in one patient 48 months after surgery: stenosis occurred at a distance from the corrected site. These results confirmed that strictureplasty is a safe and efficient procedure in selected patients undergoing surgery for obstructive Crohn's disease.

A new technique for combined liver/small intestinal transplantation.

The most common application of small bowel transplantation is for the patient with parenteral nutrition-induced liver failure. In this setting, the small intestine is transplanted simultaneously with the liver. We identified three technical problems that we believe contributed to complications in our first eight patients. First, pancreaticoduodenectomy was challenging in the infant donor. Second, the bowel graft was prone to volvulus around the skeletonized donor portal vein. Third, in the pediatric recipient, use of the donor bowel for Roux-en-Y biliary reconstruction was associated with biliary leaks in the early postoperative period. Our surgical technique of liver/small bowel (L/SB) transplantation has evolved since our early experience in 1990. Modifications in the L/SB operation, reported briefly in 1996 and 1997, have led to easier graft preparation and have reduced the incidence of technical complications.

Treatment of multiple aneurysms of the splenic artery after liver transplantation by percutaneous embolization and laparoscopic splenectomy.

A high incidence of aneurysms of the splenic artery is found in liver transplant patients. Their significance is related to the risk of rupture, particularly in the postoperative period. Classically, their management is surgical, with ligation or resection of the aneurysmal arterial segment with or without splenectomy, depending on the location of the aneurysm. Recently, laparoscopy and percutaneous embolization have appeared as alternative treatment options. We describe here the treatment of multiple aneurysms of the splenic artery in a patient who had undergone liver transplantation 10 years earlier. She was treated with percutaneous embolization of the aneurysms followed by laparoscopic splenectomy. To our knowledge, this is the first report of laparoscopic splenectomy following liver transplantation. It demonstrates that prior liver transplantation does not represent an absolute contraindication to minimally invasive surgery.

Seventy-two hours hypothermic intestinal preservation study using a new perfluorocarbon emulsion.

We investigated the effect of a perfluorocarbon emulsion (FC) added to the University of Wisconsin (UW) solution on hypothermic (4 degrees C, 12-72h) preservation of rat small bowel grafts. The FC was 90%w/v perfluorooctylbromide, 2%w/v egg yolk phospholipids and 1.4%w/v mixed fluorocarbon-hydrocarbon molecular dowels. Four groups were defined: [1] UW flush and UW storage; [2] UW flush and FC storage; [3] flush with FC diluted 2 times with UW (FU) and FU storage; [4] FU flush and storage in oxygenated FU. Preservation was estimated with a histological score based on villus epithelium adhesion, on villus sloughing and on crypt cell adhesion to the basal membrane. Antioxidant potential was estimated by measurement of total thiol functions (SH) and activities of glutathione-peroxidase (GSH-P), superoxide dismutase (SOD) and catalase. FC in flush improved preservation during the first 24h (p<0.01). Storage in FC appeared superior to UW for the first 24h (p<0.01). Oxygenation (100% O2) of the storage medium yielded superior results at 12h and 24h (p<0.01 and p<0.001 versus group [1] respectively). After 72h, SOD and catalase activities increased in groups [3] and [4], and SOD decreased in group [1] (p<0.05). SH progressively decreased in group [1] (p<0.05) and GSH-P increased at 24 and 48h in groups [3] and [4] (p<0.01). The increase of O2 in the perfusion flush or storage medium ameliorated the preservation status and protected the antioxidant potential of the small bowel.

Pseudoaneurysm of the Y-graft/iliac artery anastomosis following pancreas transplantation: a case report and review of the literature.

Transplant-related aneurysms are an unusual complication following pancreas transplantation. We present a case of a pseudoaneurysm developing in a recipient 6 months after bladder-drained pancreas transplantation. The pseudoaneurysm was incidentally found during ultrasonographic evaluation in preparation for a pancreas biopsy. Angiography demonstrated that the origin of the pseudoaneurysm was located near the base of the Y-graft/iliac artery anastomosis. Surgical repair was performed using standard vascular techniques. The patient subsequently recovered without loss of graft exocrine or endocrine function. Review of the literature revealed that aneurysms of various types associated with pancreas transplantation have a high incidence of graft loss and contribute significantly to patient morbidity. However, with prompt diagnostic and surgical management, non-infected pseudoaneurysms can be repaired without loss of pancreatic function.

Renal allograft autotransplantation before pelvic irradiation.

The anatomical location of a renal allograft places the kidney in jeopardy during radiation therapy of pelvic and perineal malignancies. Alternative choices include avoiding irradiation, altering the dose, or excluding the graft from the field of radiation, with the risk of compromising the efficacy of the treatment. Transplantation of the graft out of the field of irradiation is another option. We describe the management, by allograft autotransplantation, of a renal transplant patient with an invasive carcinoma of the vulva for which postoperative inguinopelvic radiotherapy was advocated. This report underlines the technical difficulties encountered during reoperation on an allograft and the need for versatility in vascular and urologic reconstructions. With these reservations, autotransplantation permits the recovery of a normal renal function and is an option to consider in the salvage of a kidney transplant.

Immunosuppressive effect of combination schedules of brequinar with leflunomide or tacrolimus on rat cardiac allotransplantation.

Drug toxicity is one of the major problems in clinical immunosuppression. Combining two immunosuppressants in low or ineffective doses is an attractive strategy if it helps to reduce drug-related toxicity. We examined the immunosuppressive efficacy of brequinar (BQR) in combination with leflunomide (Lef) or tacrolimus (FK) in a heterotopic rat cardiac allotransplantation model. Abdominal heterotopic heart grafts (DA x LEW) were immunosuppressed from the time of transplantation and continued until the ninth posttransplant day (POD) in experiments examining prophylaxis of rejection treatment (PRT). In a separate series of experiments designed to test rescue treatment (RT), immunosuppression was begun on POD 4 and continued for 10 days; transplanted rats were sacrificed the following day intentionally. Cardiac rejection was monitored by palpation and documented by light microscopy. Immunosuppressive drugs (BQR 3 mg/kg and 12 mg/kg; BQR 3 mg/kg + Lef 5 mg/kg; BQR 3 mg/kg + FK 0.5 mg/kg) were given orally by gavage; thrice weekly according to the monotherapy or dual-therapy dosing protocol. Median survival time of the cardiac graft for controls (no treatment) was 5 days. BQR monotherapy 3 mg/kg (low dose) improved graft survival (P = 0.003); graft histology showed moderate acute rejection. BQR monotherapy 12 mg/kg (therapeutic dose) application in the PRT or RT treatment arms of the study design resulted in aortic-graft ruptures and clinical toxicity in each treatment arm due to overimmunosuppression; normal graft morphology was maintained. Successful rescue of rejecting grafts was histologically documented. Combining BQR with Lef or FK in the PRT protocol showed prolonged graft survival in both drug combination groups (median survival time, 14 days; P = 0.009 and 0.014, respectively). Using an identical combination protocol for RT, all grafts achieved a 14-day graft survival; cardiac histology showed reversible moderate acute rejection. BQR given in the presence of Lef or FK not only prevented acute rejection but intercepted it so long as it was administered; grafts were rejected within 4 days of stopping immunosuppression in the PRT study. These combinations using low or subtherapeutic doses may be important for controlling transplant rejection and rescuing ongoing graft rejection. The need for continuing treatment in this strongly allogeneic model is highlighted.