Search

Incidental gallbladder cancer (IGBC) represents 50%-60% of gallbladder cancer cases. Data are conflicting on the role of IGBC diagnosis in oncological outcomes. Some studies suggest that IGBC diagnosis does not affect outcomes, while others that overall survival (OS) is longer in these cases compared to non-incidental diagnosis (NIGBC). Furthermore, some studies reported early tumour stages and histopathologic characteristics as possible confounders, while others not.To investigate the role of IGBC diagnosis on patients' overall survival, especially after surgical treatment with curative intent.Retrospective analysis of all patient referrals with gallbladder cancer between 2008 and 2020 in a tertiary hepatobiliary centre. Statistical comparison of patient and tumour characteristics between IGBC and NIGBC subgroups was performed. Survival analysis for the whole cohort, surgical and non-surgical subgroups was done with the Kaplan-Meier method and the use of log rank test. Risk analysis was performed with univariable and multivariable Cox regression analysis.The cohort included 261 patients with gallbladder cancer. 65% of cases had NIGBC and 35% had IGBC. A total of 90 patients received surgical treatment (66% of IGBC cases and 19% of NIGBC cases). NIGBC patients had more advanced T stage and required more extensive resections than IGBC ones. OS was longer in patients with IGBC in the whole cohort (29IGBC diagnosis may confer a survival advantage independently of the pathological stage and tumour characteristics. Prospective studies are required to further investigate this, including detailed pathological analysis and molecular gene expression.

Background Oncological outcomes are comparable between octogenarians and younger patients after pancreatoduodenectomy for pancreatic ductal adenocarcinoma Methods A multicentre case-control study of octogenarians matched on complexity of surgery with consecutive younger controls who underwent PD for PDAC (2008–2017). Results Some 220 patients were included, 110 octogenarians (age 81 (80–83)) and 110 controls (age 69 (62–74)). Charlson Comorbidity Index score was higher in octogenarians than controls (7 (6–8) vs 5 (4–6)), p Conclusions In selected fit octogenarians, equivalent survival is achievable. Centralisation and multimodal therapy are key. Pre-operative risk stratification using at ECOG and albumin level can be used to identify an appropriate population.

Background Pancreaticoduodenectomy (PD) with vein resection is the only potentially curative option for patients with pancreatic ductal adenocarcinoma (PDAC) with venous involvement. The aim of our study was to assess the oncological prognostic significance of the different variables of venous involvement in patients undergoing PD for resectable and borderline resectable with venous only involvement (BR-V) PDAC. Methods Retrospective analysis of prospectively maintained PD database from 2011–2020 was performed. Standard descriptive statistical analysis; statistical comparisons with the use of the appropriate test; survival analysis with the Kaplan-Meier method and log rank test for overall survival (OS), disease-free survival (DFS) and local recurrence (LR); risk analysis for separate surgicalmargins with univariable and multivariable Cox proportional hazard model were used. Results One hundred and five of 372 patients (28%) required vein resection and vein wall involvement was identified in 37% of those. More vein resections were performed in female patients and as expected for BR-V disease. OS, DFS and LR were significantly longer after R0 resection, irrespective of the need for a venous resection. Following analysis of separate surgical margins, the vein groove and the vein transection margins (the latter only applicable in patients that had a venous resection) were not identified as predictors of oncological outcomes. On the contrary, vein wall invasion was an independent predictor of OS (HR:1.947, CI: 1.228–3.089, p=0.005), DFS (HR: 2.169, CI: 1.306–3.602, p=0.003) and LR (HR: 2.365, CI: 1.089–5.133, p=0.030) after PD with venous resection. Conclusions Vein wall tumour invasion may be a more reliable predictor of oncological outcomes compared to traditionally reported parameters. Future studies should focus on possible pre-operative investigations that could identify these cases and management pathways that could yield survival benefit, such as the use of neoadjuvant treatments.

Prompt diagnosis of vascular compromise following pediatric liver transplantation and restoration of oxygen delivery to the liver improves organ survival. vis-DRS allows for real-time measurement of liver tissue saturation.The current study used vis-DRS to determine changes in liver saturation during clinically relevant conditions of reduced oxygen delivery. In an in vivo swine model (n = 15), we determined liver tissue saturation (SLiver tissue saturation decreased significantly with a decrease in hepatic artery flow. A reduction in hepatic artery flow to 25% of baseline reduced the SVis-DRS showed prompt changes in liver tissue saturation with decreases in hepatic artery blood flow. At hepatic artery flows below 50% of baseline, liver saturation depended on FiO2 and hemoglobin concentration suggesting that during hepatic artery occlusion, packed red blood cell transfusion and increased FiO

Para-aortic lymph nodes (PALN) are found in the aortocaval groove and they are staged as metastatic disease if involved by pancreatic ductal adenocarcinoma (PDAC). The data in the literature is conflicting with some studies having associated PALN involvement with poor prognosis, while others not sharing the same results. PALN resection is not included in the standard lymphadenectomy during pancreatic resections as per the International Study Group for Pancreatic Surgery and there is no consensus on the management of these cases.To investigate the prognostic significance of PALN metastases on the oncological outcomes after resection for PDAC.This is a retrospective cohort study of data retrieved from a prospectively maintained database on consecutive patients undergoing pancreatectomies for PDAC where PALN was sampled between 2011 and 2020. Statistical comparison of the data between PALN+ and PALN- subgroups, survival analysis with the Kaplan-Meier method and risk analysis with univariable and multivariable time to event Cox regression analysis were performed, specifically assessing oncological outcomes such as median overall survival (OS) and disease-free survival (DFS).81 cases had PALN sampling and 17 (21%) were positive. Pathological N stage was significantly different between PALN+ and PALN- patients (PALN involvement does not affect OS when patients complete the indicated treatment pathway for PDAC, surgery and chemotherapy, and should not be considered as a contraindication to resection.

Historically, locally advanced pancreatic adenocarcinoma (LAPDAC) was considered a palliative condition. Advances in treatment have resulted in studies reporting survival after neoadjuvant treatment and surgery similar to earlier disease stages. However, there is no consensus on optimal LAPDAC management. Our aim was a systematic review of published evidence on LAPDAC treatment strategies with curative intent. Twenty-eight studies defining LAPDAC as per established criteria and reporting outcomes after neoadjuvant treatment with a view to resection were included. Primary outcomes were resection rate and proportion of curative resections. Secondary outcomes were postoperative mortality, progression-free survival, and overall survival. Neoadjuvant treatment varied significantly, most common being the combination of folinic acid, fluorouracil, irontecan, and oxaliplatin. Median percentage of patients proceeding to surgery after completion of neoadjuvant pathway was 33.5%. Median resection rate was 25%. Median R0 resection was 80% of resected patients. These outcomes ranged 0% to 100% across studies. Ninety-day postoperative mortality ranged from 0% to 5%. Median progression-free and overall survival for resected patients were 12.9 and 30 months, respectively, versus 13.2 months overall survival for unresected patients. In conclusion, although there is wide variability in reported LAPDAC resection rates post-neoadjuvant chemotherapy, retrospective data suggest that neoadjuvant treatment followed by surgery results in improved survival.

Pancreaticoduodenectomy (PD) is the commonest procedure performed for pancreatic cancer. Pancreatic exocrine insufficiency (PEI) may be caused or exacerbated by surgery and remains underdiagnosed and undertreated. The aim of this review was to ascertain the incidence of PEI, its consequences and management in the setting of PD for indications other than chronic pancreatitis. A literature search of databases (MEDLINE, EMBASE, Cochrane and Scopus) was carried out with the MeSH terms "pancreatic exocrine insufficiency" and "Pancreaticoduodenectomy". Studies that analysed PEI and its complications in the setting of PD for malignant and benign disease were included. Studies reporting PEI in the setting of PD for chronic pancreatitis, conference abstracts and reviews were excluded. The incidence of PEI approached 100% following PD in some series. The pre-operative incidence varied depending on the characteristics of the patient cohort and it was higher (46%-93%) in series where pancreatic cancer was the predominant indication for surgery. Variability was also recorded with regards to the method used for the diagnosis and evaluation of pancreatic function and malabsorption. Pancreatic enzyme replacement therapy is the mainstay of the management. PEI is common and remains undertreated after PD. Future studies are required for the identification of a well-tolerated, reliable and reproducible diagnostic test in this setting.

Background Patients with locally advanced pancreatic cancer have historically been considered inoperable. The purpose of this report was to determine resectability rates for patients with locally advanced pancreatic cancer based on our recently described definitions of type A and type B locally advanced pancreatic cancer. Methods An institutional prospective pancreas cancer database was queried for consecutive patients with locally advanced pancreatic cancer treated between January 2009 and June 2017. All pretreatment imaging was re-reviewed and patients were categorized as locally advanced pancreatic cancer type A or type B. Demographics, induction therapy, resection type, and outcomes were reviewed. Results We identified 108 consecutive patients; 12 were excluded from analysis due to the absence of available pretreatment imaging or they had not yet completed all intended neoadjuvant therapy. Of the remaining 96 patients (45 type A, 51 type B), disease progression occurred in 19 (20%) during induction therapy and 30 (31%) were deemed inoperable at final preoperative restaging. Therefore, 47 (49%) of 96 patients were taken to surgery and 40 (42%) underwent successful resection (28 [62%] of 45 type A and 12 [24%] of 51 type B); an RO resection was achieved in 32 (80%). Metastatic disease was found intraoperatively (6 at laparoscopy, 1 at laparotomy) in 7 (15%) of 47 patients. There were no mortalities; 6 (15%) patients experienced major postoperative complications. Resected patients had a median overall survival of 38.9 months. Conclusion Locally advanced pancreatic cancer can be dichotomized into type A and B with distinctly different probabilities of completing all therapy to include surgery; thereby allowing goals of therapy to be established at the time of diagnosis. Multimodality therapy that includes surgery can be accomplished in selected patients with locally advanced pancreatic cancer and is associated with a median overall survival that approximates earlier stages of disease. (Surgery 2017;160:XXX-XXX.)

The successful outcome in orthotopic liver transplantation (OLT) is critically dependent on the uncompromised hepatic graft blood inflow. Arterial conduits represent a good solution in cases where conventional revascularisation is not possible. The purpose of this systematic review is to analyse the published evidence on the use of arterial conduits in adult OLT. After review of the Pubmed and EMBASE databases, 19 relevant studies were identified and analysed. Even though patient survival was comparable, most large studies reported worse 1-, 3- and 5-year graft survival rates compared to grafts with standard arterial revascularisation. Primary grafts were more commonly affected than re-grafts. Early and late hepatic artery thrombosis occurred more commonly, while the use of an arterial conduit was identified as an independent risk factor. The overall biliary complications were comparable, however, ischaemic cholangiopathy was encountered about 3 times more in patients with arterial conduits and strongly correlated with the occurrence of late HAT. In conclusion, the use of arterial conduit is a useful option in adult OLT in cases that the conventional revascularisation technique cannot be used or results in suboptimal arterial inflow. More studies directly addressing issues such as pre-operative evaluation regarding the need for arterial conduit, the types of vessels used, positioning of the conduit and post-operative management are required.

Highlights • IPDA aneurysms associated with coeliac axis occlusion are rare. • Management includes radiologically guided endovascular approach or surgical repair. • Given mortalities of greater than 50% with rupture, intervention is indicated. • We present a case of a surgical repair with a supra-coeliac aorto-hepatic bypass., Introduction Inferior pancreatico-duodenal artery (IPDA) aneurysms are very rare and commonly associated with coeliac axis stenosis or occlusion due to atherosclerosis, thrombosis or median arcuate ligament syndrome. We present a case of a surgical repair of an IPDA aneurysm with the use of a supra-coeliac aorto-hepatic bypass with a polytetrafluoroethylene (PTFE) graft, following a failed initial attempt at an endovascular repair. Presentation A 75 year old female, who was under investigation for night sweats, was referred to our team with an incidental finding of a 19 mm fusiform IPDA aneurysm. Initial attempt at endovascular coiling of the aneurysm was unsuccessful. Elective surgical repair involved excision of the aneurysm and to restore arterial inflow to the hepatic artery, a PTFE bypass graft was used from the supra-coeliac aorta to the hepatic artery. The patient was well 2 months following the procedure with a patent graft shown on contrast enhanced computer tomography (ceCT). Discussion Management options for IPDA aneurysms include radiologically guided endovascular approach or surgical repair. Given the high mortality of greater than 50% with ruptured aneurysms intervention is indicated in all detected cases. Conclusion Surgical excision with bypass grafting from the supra-coeliac aorta, as reported by our team, represents a satisfactory management option in patients where interventional approaches have failed or are not appropriate.

SummaryAim Peri-operative hyperglycaemia is associated with an increased incidence of adverse outcomes. Communication between primary and secondary care is paramount to minimise these harms. National guidance in the UK recommends that the glycated haemoglobin (HbA1c) should be measured within 3 months prior to surgery and that the concentration should be less that 69 mmol/mol (8.5%). In addition, national guidance outlines the minimum dataset that should be included in any letter at the time of referral to the surgeons. Currently, it is unclear how well this process is being carried out. This study investigated the quality of information being handed over during the referral from primary care to surgical outpatients within the East of England. Methods Primary care referrals to nine different NHS hospital Trusts were gathered over a 1-week period. All age groups were included from 11 different surgical specialties. Referral letters were analysed using a standardised data collection tool based on the national guidelines. Results A total of 1919 referrals were received, of whom 169 (8.8%) had previously diagnosed diabetes mellitus (DM). However, of these, 38 made no mention of DM in the referral letter but were on glucose-lowering agents. Only 13 (7.7%) referrals for patients with DM contained a recent HbA1c, and 20 (11.8%) contained no documentation of glucose-lowering medication. Conclusion This study has shown that the quality of referral letters to surgical specialties for patients with DM in the East of England remain inadequate. There is a clear need for improving the quality of clinical data contained within referral letters from primary care. In addition, we have shown that the rate of referral for surgery for people with diabetes is almost 50% higher than the background population with diabetes.

We have analyzed the relationship between donor mismatches at each HLA locus and development of HLA locus-specific antibodies in patients listed for repeat transplantation. HLA antibody screening was undertaken using single-antigen beads in 131 kidney transplant recipients returning to the transplant waiting list following first graft failure. The number of HLA mismatches and the calculated reaction frequency of antibody reactivity against 10,000 consecutive deceased organ donors were determined for each HLA locus. Two-thirds of patients awaiting repeat transplantation were sensitized (calculated reaction frequency over 15%) and half were highly sensitized (calculated reaction frequency of 85% and greater). Antibody levels peaked after re-listing for repeat transplantation, were independent of graft nephrectomy and were associated with length of time on the waiting list (odds ratio 8.4) and with maintenance on dual immunosuppression (odds ratio 0.2). Sensitization was independently associated with increasing number of donor HLA mismatches (odds ratio 1.4). All mismatched HLA loci contributed to the development of HLA locus-specific antibodies (HLA-A: odds ratio 3.2, HLA-B: odds ratio 3.4, HLA-C: odds ratio 2.5, HLA-DRB1: odds ratio 3.5, HLA-DRB3/4/5: odds ratio 3.9, and HLA-DQ: odds ratio 3.0 (all significant)). Thus, the risk of allosensitization following failure of a first renal transplant increases incrementally with the number of mismatches at all HLA loci assessed. Maintenance of re-listed patients on dual immunosuppression was associated with a reduced risk of sensitization.

Introduction. Single incision laparoscopic surgery (SILS) has gained increasing support over the last few years. The aim of this narrative review is to analyse the published evidence on the use and potential benefits of SILS in hepatic and pancreatic resectional surgery for benign and malignant pathology.Methods. Pubmed and Embase databases were searched using the search terms “single incision laparoscopic”, “single port laparoscopic”, “liver surgery”, and “pancreas surgery”.Results. Twenty relevant manuscripts for liver and 9 for pancreatic SILS resections were identified. With regard to liver surgery, despite the lack of comparative studies with other minimal invasive techniques, outcomes have been acceptable when certain limitations are taken into account. For pancreatic resections, when compared to the conventional laparoscopic approach, SILS produced comparable results with regard to intra- and postoperative parameters, including length of hospitalisation and complications. Similarly, the results were comparable to robotic pancreatectomies, with the exception of the longer operative time reported with the robotic approach.Discussion. Despite the limitations, the published evidence supports that SILS is safe and feasible for liver and pancreatic resections when performed by experienced teams in the tertiary setting. However, no substantial benefit has been identified yet, especially compared to other minimal invasive techniques.

Aim To investigate the outcomes of liver and pancreatic resections for renal cell carcinoma (RCC) metastatic disease. Methods This is a retrospective, single centre review of liver and/or pancreatic resections for RCC metastases between January 2003 and December 2015. Descriptive statistical analysis and survival analysis using the Kaplan-Meier estimation were performed. Results Thirteen patients had 7 pancreatic and 7 liver resections, with median follow-up 33 mo (range: 3-98). Postoperative complications were recorded in 5 cases, with no postoperative mortality. Three patients after hepatic and 5 after pancreatic resection developed recurrent disease. Median overall survival was 94 mo (range: 23-94) after liver and 98 mo (range: 3-98) after pancreatic resection. Disease-free survival was 10 mo (range 3-55) after liver and 28 mo (range 3-53) after pancreatic resection. Conclusion Our study shows that despite the high incidence of recurrence, long term survival can be achieved with resection of hepatic and pancreatic RCC metastases in selected cases and should be considered as a management option in patients with oligometastatic disease.

Chatzizacharias NA, Vaidya A, Sinha S, Sharples E, Smith R, Jones G, Brockmann J, Friend PJ. Risk analysis for deterioration of renal function after pancreas alone transplant. Clin Transplant 2011 DOI: 10.1111/j.1399-0012.2011.01534.x. © 2011 John Wiley & Sons A/S. Abstract: The risk of progression to renal replacement after pancreas transplant alone (PTA) is a concern in patients with pre-transplant estimated glomerular filtration rate (eGFR) 12 mg/dL) at six months post-transplant was the only independent risk factor identifying a substantial decline in native renal function by Cox regression analysis (HR = 14.300, CI = 1.271-160.907, p = 0.031). The presence of severe pre-transplant proteinuria (urine Pr/Cr ≥100 mg/mmol) marginally failed to reach significance (p = 0.056). Low eGFR levels alone (≤45 and ≤40 mL/min/1.73 m(2) ) at the time of transplant did not correlate with substantial decline in renal function. Our data suggest that PTA is a justifiable therapy for patients with hypoglycemia unawareness or other life-threatening diabetic complications, even in those with borderline renal function, provided that they do not suffer from severe proteinuria and appropriate monitoring and tailoring of immunosuppression is ensured. © 2011 John Wiley & Sons A/S.

The effect of pancreas transplantation on renal function remains a matter of debate. The purpose of this retrospective, single-unit study is a preliminary analysis of renal function one yr after pancreas transplant (pancreas alone [PTA] or pancreas after kidney [PAK]). Fifty-nine patients were included. Serum creatinine and estimated glomerular filtration rate (eGFR) levels were compared three, six, and 12 months post-transplantation for the whole sample and separately for PTA and PAK and high (>45 mL/min/1.73 m(2)) and low (≤45 mL/min/1.73 m(2)) pre-transplant eGFR subgroups. Overall, eGFR did not change significantly (p = 0.228) at the end of the first year post-transplant, with patients of low initial eGFR presenting a more prominent trend toward stable or improved levels. In the PAK subgroup, eGFR was significantly improved (p = 0.035). High eGFR subgroup demonstrated no significant deterioration in renal function, while patients with low initial eGFR had significantly higher levels 3 (p = 0.012) and six months (p = 0.009) post-transplant. Our study shows that renal function did not deteriorate significantly one yr after pancreas transplant (PTA or PAK), even in patients with substantial pre-existing renal dysfunction. Evaluation at a wider scale and identification of risk factors for potential deterioration are challenges for future research.

Focal Adhesion Kinase (FAK) is a protein tyrosine kinase, localised in the focal adhesions, which, upon activation interacts with Src, another tyrosine kinase, regulating several cellular signalling pathways. Both enzymes have been implicated in malignant transformation and disease progression. The aim of the present study was to evaluate the clinical significance of FAK and Src expression in cases of endometrial adenocarcinoma. The total (t) and the activated, phosphorylated (p) forms of FAK and Src proteins were assessed immunohistochemically in tumour specimens obtained from 43 endometrial adenocarcinoma patients and were statistically analyzed in relation to various clinicopathological parameters and tumour proliferative capacity, reflected by Ki-67 labelling index. t-FAK positivity was significantly correlated with FIGO disease stage (p = 0.031), and t-FAK overexpression with patients' age (p = 0.015). No statistically significant correlation was identified between t-FAK staining intensity, t-Src positivity, overexpression or staining intensity and any of the clinicopathological parameters tested. No significant correlation was found between neither the positivity nor the intensity of staining of either p-FAk or p-Src with any of the parameters under study. Nonetheless, important, but non-significant, trends were identified between t-FAK staining intensity, t-Src positivity and overexpression and patients' survival (log rank, p = 0.122, p = 0.090 and p = 0.057 respectively). Similarly, p-FAK and p-Src staining characteristics seemed to correlate, even though non-significantly, with patients' survival (log rank, p = 0.051 and p = 0.070 for p-FAK and p-Src expression, respectively; log rank, p = 0.134 and p = 0.110 for p-FAK and p-Src staining intensity, respectively). These results support an important potential role of FAK-Src signalling in endometrial malignant disease progress and render further research in this field a necessity.

Objectives Focal adhesion kinase (FAK) and Src, 2 protein tyrosine kinases, have been suggested to regulate several fundamental cellular activities that promote the malignant phenotype in various human tumors, including pancreatic adenocarcinoma. Even though research has already turned in laboratory investigations and clinical trials on the possible use of agents blocking the 2 enzymes in cancer management, the data on the clinical significance of FAK and Src in pancreatic adenocarcinoma are still scarce. Methods The FAK and Src protein expression was assessed immunohistochemically in tumor specimens of 65 patients with pancreatic ductal adenocarcinoma and was statistically analyzed in relation to various clinicopathological characteristics, tumor proliferative capacity, and patients' survival. Results The FAK expression correlated significantly with the T stage of the tumor (P = 0.037), whereas FAK staining intensity with patients' age (P = 0.030), tumors' histopathological grade of differentiation (P = 0.041), and M stage (P = 0.029). The Src expression correlated significantly with the stage of the tumor (P = 0.013) and patients' survival (log-rank test, P = 0.027), being also identified as an independent prognostic factor in multivariate analysis (P = 0.047). Furthermore, trends that did not reach statistical significance were noted between FAK and Src expression and staining intensity and several clinicopathological parameters. Conclusions The FAK and Src immunohistochemical expression was associated with certain clinicopathological parameters that are crucial for the patients' management.

Rhabdomyosarcoma (RMS) is the most common soft tissue tumour in children. This is the first time a facial RMS metastatic to the pancreas is reported. The patient was a 3-year-old boy with a symptomatic solitary pancreatic metastasis of a primary facial RMS, with already one relapse in a submental lymph node. Since this was the second relapse of the disease and due to the extensive nature of the mass, the patient was considered for palliative care and a bypass procedure with a choledochojejunostomy, a gastrojejunostomy and a cholecystectomy was performed. The patient expired 6 months later.

Introduction. Intussusception is a rare cause of bowel obstruction in adults and is usually associated with an underlying pathology, benign, or malignant. This is a report of a case of jejunojejunal intussusception secondary to non-Hodgkin’s B-cell lymphoma in an adult patient.Case Presentation. A 74-year-old male with no previous significant medical history presented with symptoms of acute intestinal obstruction. A CT scan of the abdomen and pelvis revealed 2 areas of jejunojejunal intussusception, which were surgically managed successfully. Histopathological examination of the specimen revealed the presence of high grade diffuse large B-cell-type non-Hodgkin’s lymphoma, and the patient was referred to the oncology team for further management.Discussion. B-cell lymphoma is a rare but well-documented cause of intussusception in adults, with most cases being at the ileocolic region. We present a rare case of jejunojejunal intussusception as the initial presentation of non-Hodgkin’s B-cell lymphoma in an adult patient.

Acute umbilical hernia rupture in patients with hepatic cirrhosis and ascites is an unusual, but potentially life-threatening complication, with postoperative morbidity about 70% and mortality between 60%-80% after supportive care and 6%-20% after urgent surgical repair. Management options include primary surgical repair with or without concomitant portal venous system decompression for the control of the ascites. We present a retrospective analysis of our centre’s experience over the last 6 years. Our cohort consisted of 11 consecutive patients (median age: 53 years, range: 36-63 years) with advanced hepatic cirrhosis and refractory ascites. Appropriate patient resuscitation and optimisation with intravenous fluids, prophylactic antibiotics and local measures was instituted. One failed attempt for conservative management was followed by a successful primary repair. In all cases, with one exception, a primary repair with non-absorbable Nylon, interrupted sutures, without mesh, was performed. The perioperative complication rate was 25% and the recurrence rate 8.3%. No mortality was recorded. Median length of hospital stay was 14 d (range: 4-31 d). Based on our experience, the management of ruptured umbilical hernias in patients with advanced hepatic cirrhosis and refractory ascites is feasible without the use of transjugular intrahepatic portosystemic shunt routinely in the preoperative period, provided that meticulous patient optimisation is performed.

Pancreato-biliary malignancies often present with locally advanced or metastatic disease. Surgery is the mainstay of treatment although less than 20% of tumours are suitable for resection at presentation. Common sites for metastases are liver, lungs, lymph nodes and peritoneal cavity. Metastatic disease carries poor prognosis, with median survival of less than 3 mo. We report two cases where metastases from pancreato-biliary cancers were identified in the colon and anal canal. In both cases specific immunohistochemical staining was utilised in the diagnosis. In the first case, the presenting complaint was obstructive jaundice due to an ampullary tumour for which a pancreato-duodenectomy was carried out. However, the patient re-presented 4 wk later with an atypical anal fissure which was found to be metastatic deposit from the primary ampullary adenocarcinoma. In the second case, the patient presented with obstructive jaundice due to a biliary stricture. Subsequent imaging revealed sigmoid thickening, which was confirmed to be a metastatic deposit. Distal colonic and anorectal metastases from pancreato-biliary cancers are rare and can masquerade as primary colorectal tumours. The key to the diagnosis is the specific immunohistochemical profile of the intestinal lesion biopsies.

Ephrin (Eph) receptors and their membrane-anchored ligands, the ephrins, participate in a wide spectrum of pathophysiological processes, regulating cellular adhesion, migration or chemo-repulsion and tissue/cell boundary formation. Recent evidence has further extended the role of Eph receptors and their ligands as critical regulators of vascular remodelling during embryogenesis. The role of Ephs/ephrins signalling in the angiogenic development of murine placentas and in the invasion of the maternal tissues and the development of the placental vasculature in humans has currently attracted considerable interest.A literature review summarising the most recent data in terms of the role of Ephs/ephrins in normal placental development and disease, highlighting on their expression status in the different cellular populations of the placental vascularity.Despite the fact that the role of Eph/ephrins signalling in normal placental development is still unclear, some studies tried to investigate their potential implication in placental pathologies, such as preeclampsia and placenta accreta. Even though no evidence for their direct implication occurred, their role is an interesting field for future research.

Introduction: Single port laparoscopic surgery has been increasingly used for complex surgical procedures. To our knowledge, this is the first published report of a single port laparoscopic subtotal colectomy and ileostomy in an adolescent patient with ulcerative colitis. Case report: A 13-year old female patient with ulcerative colitis resistant to maximal medical therapy underwent a single port laparoscopic subtotal colectomy and ileostomy. Both the procedure and the postoperative recovery were uneventful and the patient was discharged home on the sixth postoperative day. Follow-up at 3 and 8 weeks after surgery identified no early complications with a 4 kg weight gain. Discussion: Single port laparoscopic surgery is feasible in the adolescent population if there is appropriate surgical expertise and strict patient selection.

The effect of pancreas transplantation on renal function remains a matter of debate. The purpose of this retrospective, single-unit study is a preliminary analysis of renal function one yr after pancreas transplant (pancreas alone [PTA] or pancreas after kidney [PAK]). Fifty-nine patients were included. Serum creatinine and estimated glomerular filtration rate (eGFR) levels were compared three, six, and 12 months post-transplantation for the whole sample and separately for PTA and PAK and high (45 mL/min/1.73 m(2)) and low (≤45 mL/min/1.73 m(2)) pre-transplant eGFR subgroups. Overall, eGFR did not change significantly (p = 0.228) at the end of the first year post-transplant, with patients of low initial eGFR presenting a more prominent trend toward stable or improved levels. In the PAK subgroup, eGFR was significantly improved (p = 0.035). High eGFR subgroup demonstrated no significant deterioration in renal function, while patients with low initial eGFR had significantly higher levels 3 (p = 0.012) and six months (p = 0.009) post-transplant. Our study shows that renal function did not deteriorate significantly one yr after pancreas transplant (PTA or PAK), even in patients with substantial pre-existing renal dysfunction. Evaluation at a wider scale and identification of risk factors for potential deterioration are challenges for future research.

The risk of progression to renal replacement after pancreas transplant alone (PTA) is a concern in patients with pre-transplant estimated glomerular filtration rate (eGFR)70 mL/min/1.73 m(2). This is a retrospective, single-center risk analysis of potential factors affecting renal function after PTA. Twenty-four patients, transplanted over a three-yr period, with functioning pancreatic grafts at the study's end point were included. High tacrolimus levels (12 mg/dL) at six months post-transplant was the only independent risk factor identifying a substantial decline in native renal function by Cox regression analysis (HR = 14.300, CI = 1.271-160.907, p = 0.031). The presence of severe pre-transplant proteinuria (urine Pr/Cr ≥ 100 mg/mmol) marginally failed to reach significance (p = 0.056). Low eGFR levels alone (≤ 45 and ≤ 40 mL/min/1.73 m(2)) at the time of transplant did not correlate with substantial decline in renal function. Our data suggest that PTA is a justifiable therapy for patients with hypoglycemia unawareness or other life-threatening diabetic complications, even in those with borderline renal function, provided that they do not suffer from severe proteinuria and appropriate monitoring and tailoring of immunosuppression is ensured.

Focal Adhesion Kinase (FAK) and Src have been reported to regulate tumor growth, invasion, metastasis and angiogenesis. The present study aimed to evaluate by immunohistochemistry the clinical significance of FAK and Src expression in 108 patients with benign and malignant thyroid lesions. Total FAK expression provided a distinct discrimination between malignant and benign (p = 0.00001), as well as between papillary carcinoma and hyperplastic nodules thyroid lesions (p = 0.00005), being also associated with follicular cells’ proliferative capacity (p = 0.0003). In malignant thyroid lesions, total FAK expression was associated with tumor size (p = 0.0455), and presence of capsular (p = 0.0102) and lymphatic (p = 0.0173) invasion. Total Src expression was borderline increased in cases of papillary carcinoma compared to hyperplastic nodules (p = 0.0993), being also correlated with tumor size (p = 0.0169). FAK and Src expression was ascribed to a significant extent to the phosphorylated forms of the enzymes, which provided a better discrimination between malignant and benign thyroid lesions. The current data revealed that FAK and to a lesser extent Src expression could be considered of clinical utility in thyroid neoplasia with potential use as therapeutic targets.

Focal Adhesion Kinase is a 119-121 kDa nonreceptor protein kinase widely expressed in various tissues and cell types. Several studies showed that FAK plays an important role in integrin signaling. Once activated by integrin and non-integrin stimuli, it binds and activates several other molecules, such as Src, p130Cas, Grb2, PI3K and paxillin, thus promoting signaling transduction. In normal cells FAK activity is under constant regulation by mechanisms such as gene amplification, alternative splicing and action of phosphatases. On the contrary, in vitro studies showed that in transformed cells unopposed FAK signaling promoted cancer cells' malignant characteristics. FAK was held responsible for cancer cells' uninhibited proliferation, protection from apoptosis, invasion, migration, adhesion and spreading, as well as tumor angiogenesis. Several in vivo studies supported the above observations and further correlated FAK expression with various clinicopathological parameters of several types of human malignancies. The purpose of this article is a comprehensive review of the existing data on FAK expression and signaling and their clinical significance in human malignancy.

Focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase (PTK) which acts as an early modulator in the integrin signaling cascade. FAK phosphorylation and its consequent activation regulate several basic biological cellular functions. On the contrary, dysregulation of FAK signaling is implicated in the malignant transformation of cells, as well as in nonmalignant pathological conditions. With respect to cytotoxicity, accumulating data indicate that FAK participates in the mechanism of action of the known cytotoxic reactive oxygen species (ROS). Additionally, evidence was presented that different cytotoxic substances, such as arsenic (As), lead (Pb), acrylamide, methylisothiazolinone (MIT), dichlorovinylcysteine (DCVC) and halothane, acted, at least in part, by downregulating FAK tyrosine phosphorylation, while the bacterial toxins Pasteurella multocida toxin and Escherichia coli cytotoxic necrotizing factor, have been shown to exert cytotoxic effects by inducing FAK tyrosine phosphorylation. The observation that upregulation as well as downregulation of FAK activity both result in cytotoxic effects seems contradictory. Even though a common mode of action, with respect to the dysregulation of FAK signaling, for these cytotoxic substances has not yet been discovered, a cumulative approach could be established by focusing on FAK activation and signaling cascade. According to these data, interfering with FAK signaling might be of a potential use in blocking these cytotoxic effects. Further studies are needed on the possible implication of FAK in substance-induced cytotoxicity, as well as the possibility that such effects might be hindered or even blocked by restoring FAK signaling.

Focal adhesion kinase (FAK) is a protein tyrosine kinase acting as an early modulator of the integrin signalling cascade, thus regulating various basic cellular functions. In transformed cells, upregulation of FAK protein expression and uncontroled signalling were held responsible for the promotion of malignant phenotypic characteristics, as well as resistance to chemotherapy and radiotherapy. Direct FAK targeting resulted in the inhibition of the malignant phenotype of cancer cells, whereas increased apoptotic rates of cancer cells, either used alone or in combination with conventional chemotherapeutic agents, radiotherapy or hormonal therapy. Furthermore, drugs used in cancer chemotherapy, besides their basic mode of action, were also shown to act through altering FAK signalling. Finally, positive results were noted by the transfection of cancer cells with fak mutants or genes that suppress FAK expression or activity, such as phosphatase and tensin homolog deleted on chromosome Ten (PTEN), ribonucleotide reductase M1 polypeptide (RRM1) and melanoma differentiation-associated gene-7 (mda-7). The purpose of this article is a comprehensive review of the existing data on the possible use of FAK targeting in anticancer therapy.

Although laparoscopic surgery is readily used in the management of inflammatory bowel disease (IBD) in adults, its role in the surgical treatment of IBD in the pediatric population is not well established. The aim of this narrative review was to analyze the published evidence comparing laparoscopic and open resection in the management of children and adolescents with IBD. The Pubmed and Embase databases were searched using the terms “inflammatory bowel disease,” “children,” “adolescents,” “laparoscopic,” and “colectomy.” The review identified 10 appropriate studies. Even though laparoscopic surgery generally resulted in longer operating times (between a mean of 40 and 140 min), benefits included reduced postoperative pain (mean duration of opiate use 3 vs 6 days) and reduced length of stay (median length of stay 5–8 vs 10.5–19 days) compared with open surgery. Postoperative complication rates were similar following both approaches. Due to the limited available data and the small sample size of the published series, definite recommendations are not able to be drawn. Nevertheless, current evidence indicates that laparoscopic colorectal resection is safe and feasible in the management of IBD in the paediatric population, with reductions in postoperative pain and length of hospital stay achievable.

Pancreatic cancer is known for its typically late presentation and poor survival rates, with overall 5-year survival of less than 5%. The role of chemotherapy alone or with radiotherapy in the management of locally advanced tumors continues to be an area of debate. We report a case of locally advanced, pancreatic adenosquamous carcinoma that was initially deemed unresectable intraoperatively. Nonetheless, the tumor was resected after radiological response to gemcitabine-capecitabine chemoradiotherapy regimen similar to the Selective Chemoradiation in Advanced LOcalised Pancreatic cancer trial. Histological examination revealed complete pathological response with extensive fibrosis (ypT0 N0). On 12-month follow-up CT, a single liver lesion in the left lateral segment was identified and confirmed to be a metastasis with cytological diagnosis via EUS and FNA. The disease remained stable and confined to the solitary hepatic metastasis after further gemcitabine chemotherapy. Therefore, a further successful resection was performed. The 2 main strategies for the management of locally advanced unresectable pancreatic cancer are chemotherapy induction followed by consolidation chemoradiotherapy or chemotherapy alone, with conflicting published evidence. Evidence for the optimal management of the rare histological type of adenosquamous carcinoma is scant. We present a case of such tumor with a complete pathological response to chemoradiotherapy. The results of future studies in the area are eagerly awaited.