Shahid Farid

Correlation between postoperative infective complications and long-term outcomes after hepatic resection for colorectal liver metastasis.

Background:The impact of postoperative morbidity, and in particular infective complications on long-term outcomes, following hepatic resection for colorectal liver metastasis (CRLM) is not widely published. Objective:To evaluate the effect of postoperative complications on disease recurrence and overall survival in patients undergoing hepatic resection for CRLM. Methods:All patients undergoing hepatic resection for CRLM from January 1993 and March 2007 were identified, and postoperative complications analyzed. Patients who died of postoperative complications within 30 days of surgery were excluded form the study. Postoperative complications were graded using a validated system of classification. Complications were further classified into infective and noninfective complication groups and the primary end points of the study were disease free survival (DFS) and overall survival (OS) at 5 years. Result:A total of 705 patients underwent hepatic resection in the study period. Median follow-up was 38 months. Operative morbidity and mortality were 28% and 3.6%, respectively. The total number of patients was 197 (28%) with complications, and 508 (72%) without complications. The 5 year DFS and OS for those with and without complications were: 13% versus 26% (P < 0.001) and 24% versus 37% (P < 0.001), respectively. Multivariate analysis showed inflammatory response to tumor score, blood transfusion, tumor number >8, and postoperative sepsis to be independent factors associated with DFS, and inflammatory response to tumor, tumor number >8, and postoperative sepsis to be independent predictors for OS. Intra-abdominal and respiratory infection but not wound infections were associated with poorer long-term outcomes. Conclusions:Postoperative complications influence long-term outcomes in hepatic resection for CRLM. Specifically, postoperative sepsis is an independent predictor of disease free and overall survival. Thorough preoperative optimization, meticulous surgical technique and careful management in the postoperative period may reduce the incidence of these complications and influence long-term outcomes.

Acceptable Outcome After Kidney Transplantation Using Expanded Criteria Donor Grafts

Introduction. With the worldwide shortage of donors, extra lengths are ongoing to enlarge the donor pool. One means has been a greater use of “expanded criteria donor” (ECD) grafts. A major concern regarding ECD kidneys is poor long-term graft survival. The aims of this study were to determine whether ECD grafts, as defined by the United Network for Organ Sharing, had a negative impact on graft survival and to identify the principle donor and recipient factors that influenced graft survival in our patient cohort. Methods. We analyzed all deceased donor renal transplants in our unit from January 1995 to October 2005, in total 1053 transplants. Results. ECD grafts (United Network for Organ Sharing criteria) demonstrated higher rates of delayed graft function and higher early mean creatinine levels. However, there was no significant difference in 5-year graft survival. Multivariate analysis of our patient group identified donor hypertension and ischemic heart disease (IHD) as independent predictors of poor graft survival. Recipient age was significant on univariate but not on multivariate analysis. However, although younger recipients maintained acceptable 5-year graft survival despite donor hypertension, IHD, or a combination of both, these factors significantly reduced graft survival in older recipients. Conclusion. Although ECD grafts had slightly worse function, 5-year survival was comparable with standard grafts in all recipients. Donor hypertension, IHD, or a combination of both significantly reduced graft survival in older recipients, not evident in younger patients. We discuss the possible factors for improved outcome with ECD grafts in our patients and the implications of our patient analysis.

Evolution of the surgical management of perihilar cholangiocarcinoma in a Western centre demonstrates improved survival with endoscopic biliary drainage and reduced use of blood transfusion

BACKGROUND Perihilar cholangiocarcinoma (PHCCA) remains a surgical challenge for which few large Western series have been reported. The aims of this study were to investigate the results of surgical resection for PHCCA and assess how practice has evolved over the past 15 years. METHODS A prospectively maintained database was interrogated to identify all resections. Clinicopathological data were analysed for impact on survival. Subsequently, data for resections carried out during the periods 1994-1998, 1999-2003 and 2004-2008 were compared. RESULTS Eighty-three patients underwent resection. Trisectionectomy was required in 67% of resections. Overall survival was 70%, 36% and 20% at 1, 3 and 5 years, respectively. Size of tumour, margin (R0) status, lymph node status, distant metastasis, tumour grade, portal vein resection, microscopic direct vascular invasion, T-stage and blood transfusion requirement significantly affected outcome on univariate analysis. Distant metastasis (P = 0.040), percutaneous biliary drainage (P = 0.015) and blood transfusion requirement (P = 0.026) were significant factors on multivariate analysis. Survival outcomes improved and blood transfusion requirement was significantly reduced in the most recent time period. DISCUSSION Blood transfusion requirement and preoperative percutaneous biliary drainage were identified as independent indicators of a poor prognosis following resection of PHCCA. Longterm survival can be achieved following the aggressive surgical resection of this tumour, but the emergence of a clear learning curve in our analyses indicates that these patients should be managed in high-volume centres in order to achieve improved outcomes.

Shotgun proteomics of human bile in hilar cholangiocarcinoma

The need to find biomarkers for hepatobiliary diseases including cholangiocarcinoma (CCA) has led to an interest in using bile as a proximal fluid in biomarker discovery experiments, although there are inherent challenges both in its acquisition and analysis. The study described here greatly extends previous studies that have started to characterise the bile proteome. Bile from four patients with hilar CCA was depleted of albumin and immunoglobulin G and analysed by GeLC‐MS/MS. The number of proteins identified per bile sample was between 378 and 741. Overall, the products of 813 unique genes were identified, considerably extending current knowledge of the malignant bile proteome. Of these, 268 were present in at least 3 out of 4 patients. This data set represents the largest catalogue of bile proteins to date and together with other studies in the literature constitutes an important prelude to the potential promise of expression proteomics and subsequent validation studies in CCA biomarker discovery.

Prognostic value of the lymph node ratio after resection of periampullary carcinomas

BACKGROUND Data have indicated that the lymph node ratio (LNR) may be a better prognostic indicator than lymph node status in pancreatic cancer. OBJECTIVES To analyse the value of the LNR in patients undergoing resection for periampullary carcinomas. METHODS A cut off value of 0.2 was assigned to the LNR in accordance with published studies. The impact of histopathological factors including a LNR was analysed using Kaplan-Meier and Cox regression methods. RESULTS In total, 551 patients undergoing a resection (January 2000 to December 2010) were analysed. The median lymph node yield was 15, and 198 (34%) patients had a LNR > 0.2. In patients with a LNR of > 0.2, the median overall survival (OS) was 18 versus 33 months in patients with an LNR < 0.2 (P < 0.001). Univariate analysis demonstrated a LNR > 0.2, T and N stage, vascular or perineural invasion, grade and resection margin status to be significantly associated with OS. On multivariate analysis, only a LNR > 0.2, vascular or perineural invasion and margin positivity remained significant. In N1 disease, a LNR was able to distinguish survival in patients with a similar lymph node burden, and correlated with more aggressive tumour pathological variables. CONCLUSION A LNR > 0.2, and not lymph note status, is an independent prognostic factor for OS indicating the LNR should be utilized in outcome stratification.

Elevated preoperative recipient neutrophil-lymphocyte ratio is associated with delayed graft function following kidney transplantation.

INTRODUCTION The neutrophil-lymphocyte ratio (NLR) is an indicator of inflammatory status. We studied the effect of preoperative elevated NLR in the recipient in relation to the risk of developing delayed graft function (DGF) after kidney transplantation. METHODS We retrospectively analysed the preoperative white blood cell count of renal transplant recipients between 2003 and 2005. An NLR >3.5 was considered elevated. There were 398 kidney transplant recipients of whom 249 received organs from donors after brain death (DBD), 61 from donors after circulatory death (DCD), and 88 from living donors. RESULTS One hundred three patients (26%) developed DGF, of which 67 (65%) had NLRs >3.5. Of 295 recipients with primary graft function, only 44 (15%) had elevated NLR. Univariate analysis revealed three factors that significantly influenced graft function: NLR >3.5, cold ischemic time (CIT) >15 hours, and donor type. On multivariate analysis, both donor type (DCD: hazard ratio [HR] = 2.421, confidence interval [CI] = 1.195-4.905, P = .014; LD: HR = 0.289, CI = 0.099-0.846, P = .024) and NLR (HR = 10.673, CI = 6.151-18.518, P < .0001) remained significant. CONCLUSIONS Elevated recipient preoperative NLR could contribute to increase the risk of developing DGF, which appears to be more pronounced in patients receiving grafts from living donors.

Successful outcome of paediatric en bloc kidney transplantation from the youngest donation-after-cardiac-death donor in the United Kingdom

We wish to highlight the successful outcome of en bloc kidney transplantation from the youngest donation after cardiac death (DCD) donor into a paediatric recipient in the United Kingdom. The donor (Maastricht Category III) was 2 years old and 12 kg male subject who died of drowning. Only kidneys were accepted for transplantation for a single recipient and were retrieved en bloc with aorta and vena cava. The recipient was a 15-year-old female subject weighing 40 kg, with end-stage renal failure secondary to familial nephritis and had a previous failed transplant caused by renal vein thrombosis. The en bloc allograft was implanted extraperitoneally in the left iliac fossa using a modification of the previously described Newcastle technique for graft implantation [1]. In their technique, the infrarenal portions of the aorta and cava are transposed to a ‘suprarenal’ position to facilitate lowering of kidneys in the pelvis and implantation of ureters of shorter length. However, as the liver was not retrieved in this case, and also as sufficient suprarenal aorta and inferior vena cava (IVC) were provided, vascular reconstruction was not required. At the back table, the aorta and IVC below the renal vessels, together with the origins of the coeliac and superior mesenteric arteries were over-sewn using 6.0 Prolene suture (Fig. 1). Graft implantation was to the external iliac vein and artery using continuous 6.0 Prolene suture. The ureters were implanted separately onto the bladder using ‘on-lay’ technique over pigtail stent using PDS sutures (Fig. 2). The first warm-, coldand second ischeamia times were 11 min, 11.5 h and 32 min respectively. Primary function was observed and postoperative recovery was uneventful. Immunosuppression consisted of tacrolimus, azathioprine and prednisolone. The patient remains well to date and 3-month creatinine was 84 lmol/l (0.95 mg/dl). The practice of transplanting paediatric en bloc kidneys is not universally accepted. Reports of increased organ discard rates, technical complications, graft thrombosis, rejection, decreased functional nephron reserve, and claims of suboptimal patient and graft survival have all contributed to the reluctance of many centres to transplant kidneys from the very young donors [2–4]. Vascular damage is not uncommon in these small kidneys and a leading cause for discard, particularly within a multiorgan procurement setting [5]. Furthermore, variable periods of first warm ischaemia, higher incidence of delayed graft function and impact on long-term graft survival associated with DCD donors mean that utilization of this source may be questioned. More recently, reports of successful outcomes of paediatric en bloc kidney transplantation into adult recipients has provided evidence of its efficacy [6–8] but its role in paediatric recipients and in the DCD setting remains controversial and little reported. Since 1988, there have been only 39 paediatric heartbeating en bloc donor kidney transplants in the United Kingdom and all into adult recipients. The mean donorand recipient ages for heart-beating en bloc donors were 3 (range 0–6 years) and 37 (range 15–72 years) years Figure 1 Graft preparation utilising a modified Newcastle technique [1]. Exclusion of the infra renal portion of the aorta and vena cava (dashed arrow) and origins of coeliac trunk and superior mesenteric artery (arrows).

Operative terminology and post-operative management approaches applied to hepatic surgery: Trainee perspectives

Outcomes in hepatic resectional surgery (HRS) have improved as a result of advances in the understanding of hepatic anatomy, improved surgical techniques, and enhanced peri-operative management. Patients are generally cared for in specialist higher-level ward settings with multidisciplinary input during the initial post-operative period, however, greater acceptance and understanding of HRS has meant that care is transferred, usually after 24-48 h, to a standard ward environment. Surgical trainees will be presented with such patients either electively as part of a hepatobiliary firm or whilst covering the service on-call, and it is therefore important to acknowledge the key points in managing HRS patients. Understanding the applied anatomy of the liver is the key to determining the extent of resection to be undertaken. Increasingly, enhanced patient pathways exist in the post-operative setting requiring focus on the delivery of high quality analgesia, careful fluid balance, nutrition and thromboprophlaxis. Complications can occur including liver, renal and respiratory failure, hemorrhage, and sepsis, all of which require prompt recognition and management. We provide an overview of the relevant terminology applied to hepatic surgery, an approach to the post-operative management, and an aid to developing an awareness of complications so as to facilitate better confidence in this complex subgroup of general surgical patients.

“OMICS” technologies and their role in foregut primary malignancies

Understanding the molecular basis of alterations in the biochemical pathways in carcinogenesis underpins developments in diagnostic, prognostic, and novel therapeutics targets. The evolving interdisciplinary field of “systems biology” attempts to provide a collective insight into complex models of disease based on various dynamic interacting networks operating at epigenetic, transcriptional, translational, and posttranslational levels. Integral to this systematic approach of profiling disease signatures (biomarkers) and cellular pathways in cancer are increasing advances in “omic technologies” (genomics, transcriptomics, proteomics, and metabolomics) and bioinformatic tools to facilitate their vast data analysis. All the platforms rely on specific analysis of DNA, RNA, protein(s), or metabolites in biological tissues or fluids and as such require different technological approaches (Fig 1). In this review, we provide an overview of the main current technologies; key terms; and results of their application in hepatocellular carcinoma (HCC), pancreatic adenocarcinoma (PCA), cholangiocarcinoma (CCA), gastric carcinoma (GC), and esophageal carcinoma (EC).

Neonatal kidney donation and transplantation: a realistic strategy for the treatment of end-stage renal disease

Charles and colleagues have highlighted an important although long ignored area of potential donation for transplantation and have explored this potential in the context of the neonatal population.1 While the diagnosis of brain stem death (BSD) remains a problem in donors under 2 months of age, there has been progress in donation after circulatory death (DCD) in the UK in this age group. We report successful outcome following renal transplantation from a 7-week-old DCD donor, with 1-year follow-up. The donor was a 7-week-old infant weighing 5 kg whose cause of death was hypoxic brain injury. The recipient was a 22-year-old female who had end-stage renal failure secondary to familial IgA nephropathy and been on peritoneal dialysis for over a year. …