Impact of portal vein infiltration and type of venous reconstruction in surgery for borderline resectable pancreatic cancer.

BACKGROUND: The International Study Group of Pancreatic Surgery (ISGPS) recommends operative exploration and resection of pancreatic cancers in the presence of reconstructable mesentericoportal axis involvement. However, there is no consensus on the ideal method of vascular reconstruction. The effect of depth of tumour invasion of the vessel wall on outcome is also unknown. METHODS: This was a retrospective cohort study of pancreaticoduodenectomy with vein resection for T3 adenocarcinoma of the head of the pancreas across nine centres. Outcome measures were overall survival based on the impact of the depth of tumour infiltration of the vessel wall, and morbidity, in-hospital mortality and overall survival between types of venous reconstruction: primary closure, end-to-end anastomosis and interposition graft. RESULTS: A total of 229 patients underwent portal vein resection; 129 (56·3 per cent) underwent primary closure, 64 (27·9 per cent) had an end-to-end anastomosis and 36 (15·7 per cent) an interposition graft. There was no difference in overall morbidity (26 (20·2 per cent), 14 (22 per cent) and 9 (25 per cent) respectively; P = 0·817) or in-hospital mortality (6 (4·7 per cent), 2 (3 per cent) and 2 (6 per cent); P = 0·826) between the three groups. One hundred and six patients (47·5 per cent) had histological evidence of vein involvement; 59 (26·5 per cent) had superficial invasion (tunica adventitia) and 47 (21·1 per cent) had deep invasion (tunica media or intima). Median survival was 18·8 months for patients who had primary closure, 27·6 months for those with an end-to-end anastomosis and 13·0 months among patients with an interposition graft. There was no significant difference in median survival between patients with superficial, deep or no histological vein involvement (20·8, 21·3 and 13·3 months respectively; P = 0·111). Venous tumour infiltration was not associated with decreased overall survival on multivariable analysis. CONCLUSION: In this study, there was no difference in morbidity between the three modes of venous reconstruction, and overall survival was similar regardless of tumour infiltration of the vein.

Prophylactic antibiotics in acute pancreatitis: endless debate.

INTRODUCTION The development of pancreatic infection is associated with the development of a deteriorating disease with subsequent high morbidity and mortality. There is agreement that in mild pancreatitis there is no need to use antibiotics; in severe pancreatitis it would appear to be a logical choice to use antibiotics to prevent secondary pancreatic infection and decrease associated mortality. MATERIALS AND METHODS A non-systematic review of current evidence, meta-analyses and randomized controlled trials was conducted to assess the role of prophylactic antibiotics in acute pancreatitis and whether it might improve morbidity and mortality in pancreatitis. RESULTS Mixed evidence was found to support and refute the role of prophylactic antibiotics in acute pancreatitis. Most studies have failed to demonstrate much benefit from its routine use. Data from our unit suggested little benefit of their routine use, and showed that the mortality of those treated with antibiotics was significantly higher compared with those not treated with antibiotics (9% vs 0%, respectively, P = 0.043). In addition, the antibiotic group had significantly higher morbidity (36% vs 5%, respectively, P = 0.002). CONCLUSIONS Antibiotics should be used in patients who develop sepsis, infected necrosis-related systemic inflammatory response syndrome, multiple organ dysfunction syndrome or pancreatic and extra-pancreatic infection. Despite the many other factors that should be considered, prompt antibiotic therapy is recommended once inflammatory markers are raised, to prevent secondary pancreatic infection. Unfortunately, there remain many unanswered questions regarding the indications for antibiotic administration and the patients who benefit from antibiotic treatment in acute pancreatitis.

Outcome of liver transplantation in patients with hereditary bleeding disorders: a single centre UK experience.

INTRODUCTION: Patients with hereditary bleeding disorders who have developed end-stage liver disease as a consequence of hepatitis C infection (HCV) acquired from factor concentrates prior to the introduction of viral inactivation continue to be referred for liver transplantation. METHODS: A retrospective review of case notes and electronic records was performed on all patients with bleeding disorders who have undergone liver transplantation at the University Hospital Birmingham (UHB). RESULTS: Between 1990 and 2014, 35 liver transplants have been performed in 33 patients with hereditary bleeding disorders. The indication for transplantation was mainly end-stage liver disease secondary to HCV. Five patients had human immunodeficiency virus (HIV) co-infection. No excess mortality due to bleeding occurred in the peri or postoperative period. Median overall survival post transplant is 9.7 years. Overall survival rates at 1, 3 and 5 years are 90%, 72% and 64% respectively. The predominant cause of mortality was liver failure secondary to either recurrent HCV or recurrent hepatocellular carcinoma (HCC). The median overall survival in patients with HIV co-infection is shorter than in those with mono-infection but this is not statistically significant. Patients with a pre-existing HCC had a statistically significant shorter survival (2.4 years vs. 13.6 years, P = 0.007). CONCLUSION: Liver transplantation has become an accepted treatment option for patients with hereditary bleeding disorders and HCV associated end-stage liver disease with survival rates similar to non-bleeding disorder patients.

Outcome after pancreaticoduodenectomy for T3 adenocarcinoma: A multivariable analysis from the UK Vascular Resection for Pancreatic Cancer Study Group.

BACKGROUND: Most resectable pancreatic cancers are classified as T3, including those involving the porto-mesenteric vein. Survival and perioperative morbidity for venous resection have been found to be comparable to standard resection. We investigate factors associated with short and long term outcomes in pancreaticoduodenectomy with (PDVR) and without (PD) venous resection exclusively for T3 adenocarcinoma of the head of the pancreas. METHODS: This is a UK multicenter retrospective cohort study assessing outcomes in patients undergoing PD and PDVR. All consecutive patients with T3 only adenocarcinoma of the head of the pancreas undergoing surgery between December 1998 and June 2011 were included. Multivariable logistic and proportional hazards regression analyses were performed to determine the association between the surgical groups and in-hospital mortality (IHM) and overall survival (OS). RESULTS: 1070 patients were included of whom 840 (78.5%) had PD and 230 (21.5%) had PDVR. Factors independently associated with IHM were a high creatinine (aHR 1.14, p = 0.02), post-operative bleeding (aHR 2.86, p = 0.04) and a re-laparotomy (aHR 8.42, p = 0.0001). For OS, multivariable analyses identified R1 resection margin status (aHR 1.22, p = 0.01), N1 nodal status (aHR 1.92, p = 0.0001), perineural invasion (aHR 1.37, p = 0.002), tumour size >20mm (aHR 0.63, p = 0.0001) and a relaparotomy (aHR 1.84, p = 0.0001) to be independently associated with overall mortality. CONCLUSION: This study on T3 adenocarcinoma of the head of the pancreas suggests that IHM is strongly associated with perioperative complications whilst OS is affected by histological parameters. Detailed pre-operative disease evaluation and advances in oncological treatment have the potential to improve OS.

Asymptomatic transmission of Treponema pallidum (syphilis) through deceased donor liver transplantation.

A 55-year-old woman underwent liver transplantation (LT) with a graft from a deceased donor. Mandatory pre-donation investigations showed positive syphilis serology that was available only after the transplant, with high Treponema pallidum particle agglutination assay titer compatible with donor syphilis infection. Despite the institution of appropriate post-exposure prophylaxis, the recipient demonstrated latent seroconversion; however, liver graft function improved without evidence of syphilitic hepatitis or other manifestations of the disease. Through this first reported case of asymptomatic transmission of syphilis following LT, we highlight the investigations and treatment strategies for donor-derived syphilis in liver transplant recipients. This report supplements the existing limited evidence on safe use of infected grafts from syphilitic donors through appropriate post-exposure prophylaxis.

Donation after cardiac death liver transplant recipients have an increased frequency of acute kidney injury.

Donation after cardiac death (DCD) liver transplantation is associated with an increased frequency of hepato-biliary complications. The implications for renal function have not been explored previously. The aims of this single-center study of 88 consecutive DCD liver transplant recipients were (1) to compare renal outcomes with propensity-risk-matched donation after brain death (DBD) patients and (2) in the DCD patients specifically to examine the risk factors for acute kidney injury (AKI; peak creatinine ≥2 times baseline) and chronic kidney disease (CKD; eGFR <60 mL/min/1.73 m(2) ). During the immediate postoperative period DCD liver transplantation was associated with an increased incidence of AKI (DCD, 53.4%; DBD 31.8%, p = 0.004). In DCD patients AKI was a risk factor for CKD (p = 0.035) and mortality (p = 0.017). The cumulative incidence of CKD by 3 years post-transplant was 53.7% and 42.1% for DCD and DBD patients, respectively (p = 0.774). Importantly, increasing peak perioperative aspartate aminotransferase, a surrogate marker of hepatic ischemia reperfusion injury, was the only consistent predictor of renal dysfunction after DCD transplantation (AKI, p < 0.001; CKD, p = 0.032). In conclusion, DCD liver transplantation is associated with an increased frequency of AKI. The findings suggest that hepatic ischemia reperfusion injury may play a critical role in the pathogenesis of post-transplant renal dysfunction.

Factors influencing outcome in patients undergoing portal vein resection for adenocarcinoma of the pancreas.

BACKGROUND: Survival rates after surgery and adjuvant chemotherapy for pancreatic ductal adenocarcinoma (PDA) remain low. Selected patients with portal/superior mesenteric vein (PV) involvement undergo PV resection at pancreaticoduodenectomy (PD). This study analyses outcomes for PD with/without PV resection in patients with PDA. METHODS: A retrospective analysis of prospectively collected data on patients requiring PD for histologically proven adenocarcinoma between 1/1997 and 9/2009 identified 326 patients with PDA, with 51 requiring PD with PV resection. Patients were analyzed in two groups: PD + PV resection vs. PD alone. Multivariate analysis was used to identify predictive variables influencing survival and the Kaplan-Meier method to estimate patient survival. RESULTS: Mean age for patients with PV resection was 66.4 (range 46-80) years, 47% were male. Both groups had similar patient demographics, perioperative and tumor characteristics. Postoperative morbidity was similar for patients with and without PV resection (27.5 vs. 28.4%). 30-day mortality was significantly higher in patients with PV resection (13.7%) vs. PD alone (5.1%). Overall survival however was similar in both groups (median PD alone 14.8 months vs. 14.5 months PD + PV). Multivariate analysis identified age, tumor grading, stay on the ICU and lack of chemotherapy as independent risk factors for reduced long-term survival. CONCLUSION: In carefully selected patients, PV resection results in similar long-term survival compared to PD alone. In selected patients, PV infiltration may be considered a sign of anatomical proximity of the tumor, rather than only a sign of increased tumor aggressiveness.

Long-term symptomatic relief following surgical sphincteroplasty for sphincter of Oddi dysfunction.

INTRODUCTION: Surgical sphincteroplasty (SS) for sphincter of Oddi dysfunction (SOD) can be performed primarily or following failed endoscopic therapy. The role of SS in an era of endoscopic management is unclear. This study presents long-term follow-up of patients who had undergone SS at a tertiary referral unit. METHODS: Patients were identified from a departmental database and sent post-operative questionnaires to review pain scores and satisfaction with the procedure. Indications, pre-operative interventions and complications were recorded. RESULTS: Seventeen patients underwent SS over 13 years. Thirteen patients had objective features of biliary obstruction (delayed excretion of isotope or elevated sphincter pressures). The positive predictive value, sensitivity and specificity of morphine 99mTc-TBIDA in this series was 100, 100 and 92%, respectively. There were 12 responders of whom all but one had symptomatic improvement. Median follow-up was 5.1 years. Pain was significantly lower following SS (16 ± 9 vs. 67 ± 11; p = 0.003) and median satisfaction with the procedure was high (95%). CONCLUSIONS: Excellent symptomatic pain relief following SS can be achieved in carefully selected patients. Manometry does not appear to be essential for diagnosing SOD and morphine provocation hepatic scintigraphy was used to reliably identify patients who would benefit from SS.

Laparoscopic posterior sectoral bile duct injury: the emerging role of nonoperative management with improved long-term results after delayed diagnosis.

BACKGROUND: Right posterior sectoral bile duct (RPSD) anomalies seen in up to 8% of the population rarely are injured at laparoscopic cholecystectomy. Paucity of data on the management of these injuries led the authors to conduct this study aimed at reviewing management strategies for laparoscopic RPSD injuries at a specialist center. METHODS: Of 221 patients, 15 (6.7%; 4 men; mean age, 51 years; range, 21-75 years) treated between 1992 and 2009 for injuries to the RPSD were followed up for a median of 58 months (range, 7-208 months). Case notes, imaging, and follow-up data were reviewed. RESULTS: The RPSD injury was immediately recognized in 3 (20%) of the 15 patients, whereas in the remaining patients, biliary injury was suspected on day 1 (range, 1-18 days) due to bile leak/biloma. The diagnosis of RPSD injury was made by a combination of investigations including endoscopic retrograde cholangiopancreatography (ERCP) (n = 11), drain tube cholangiogram (n = 10), on-table cholangiogram (n = 3), and nuclear scan (n = 3). An intact common bile duct and absence of RPSD were identified on cholangiography (ERCP and on-table cholangiogram), whereas drain tube cholangiogram demonstrated a leaking RPSD in all cases. The majority of the patients (8/15, 53%) were managed nonoperatively with combined percutaneous drainage and endoscopic stenting, whereas six patients (40%) were managed with biliary reconstruction (immediate: n = 2; delayed 14-87 days: n = 4). Clinical and radiologic confirmation of complete cessation of bile leak was demonstrated 56 days (range, 7-62 days) after injury. The long-term outcome included a dilated right duct system with transient elevation of liver function tests in two patients (1 each in the nonoperative and surgical management groups), whereas the remaining patients all remain well at this writing. CONCLUSION: Bile leak in the presence of an intact common duct shown on cholangiogram should raise the suspicion of an RPSD injury. Expertise is needed to interpret the absence of RPSD in these cases. Drain tube cholangiogram is an important adjunctive investigation. In selected cases, the results of nonoperative management alone is comparable with the results of reconstruction.

Liver resection for metastatic soft tissue sarcoma: an analysis of prognostic factors.

AIM: The aim of this retrospective study was to analyse the outcome following hepatic resection for metastatic STS and to identify factors predicting survival. METHODS: All patients who underwent hepatic resection for metastatic STS between August 1997 and April 2009 were included. The data was obtained from a prospectively maintained database. Patients' demographics, clinico-pathological parameters, overall survival and the factors predicting survival were analysed. RESULTS: Thirty-six patients underwent hepatic resection for metastasis, with a median age of 58 years. The predominant site of primary tumour was the gastro-intestinal tract (50%). Leiomyosarcoma was the most common histological type (54%). The median interval between the primary and metastatic resections was 17 months. Thirteen patients had synchronous tumours. 24 patients had major liver resections and 10 patients had bi-lobar disease. The median number of liver lesions resected was 1(1-6) and the median maximum diameter was 11 cm (1-26 cm). R0 resection was performed in 31 patients. The 1-, 3- and 5-year overall survival from the time of metastasectomy was 90.3%, 48.0% and 31.8% respectively, with a median survival of 24 months. Factors associated with poor survival on univariate analysis were the presence of high grade tumours (p = 0.04), primary leiomyosarcoma (p = 0.01) and positive resection margin of liver metastasis (p = 0.04), whilst multivariate analysis predicted primary leiomyosarcoma as a risk factor for poor survival (p = 0.01). CONCLUSION: Hepatic resection for metastatic STS appears to be valuable in carefully selected patients with acceptable long-term survival. The aim of surgery must be an R0 resection to offer a chance of cure.

Risk factors for litigation following major transectional bile duct injury sustained at laparoscopic cholecystectomy.

BACKGROUND: Bile duct injuries after laparoscopic cholecystectomy often cause long-term morbidity, with a number of patients resorting to litigation. The present study aimed to analyze risk factors for litigation and to quantify the subsequent medicolegal burden. METHODS: A total of 67/106 patients (26 male) with major laparoscopic cholecystectomy bile duct injuries (LCBDI) and a minimum 2-year follow-up, replied to a questionnaire covering patient perception toward the complication, physical/psychological recovery, and subsequent litigation. These data were collated with prospectively collected data related to the LCBDI and subsequent management, and a multivariate regression model was designed to identify potential risk factors associated with litigation. RESULTS: Most patients felt they had been inadequately informed prior to surgery [47/67 (70%)] and after the LCBDI [50/67 (75%)], and a majority remained psychologically traumatized at the time of evaluation [50/67 (75%)]. Of these, 22 patients had started litigation by means of a "letter of demand" (LOD; n = 10) or prosecution (n = 12). Nineteen (19/22%) cases have been closed in favor of the plaintiff. There was no difference between the awards for LOD versus prosecution cases, and average compensation was £40,800 versus £89,875, respectively (p = n.s). On multivariate analysis, age < 52 years (p = 0.03), associated vascular injury (p = 0.014), immediate nonspecialist repair (p = 0.009), and perceived incomplete recovery following LCBDI (p = 0.017) were identified as independent predictors for possible litigation. CONCLUSIONS: On the basis of the present study, nearly one third of patients with major transectional LCBDI are likely to resort to litigation. Younger patients and those in whom repair is attempted prior to specialist referral are likely to initiate litigation.

An unusual case of duodenal obstruction-gangliocytic paraganglioma.

Gangliocytic paragangliomas are rare tumors located in the gastrointestinal tract that are considered to be benign. They are composed of spindle-shaped cells, epithelioid cells, and ganglion-like cells. They usually present with abdominal pain, and/or gastrointestinal bleeding, and occasionally with obstructive jaundice. We report a case of obstruction in a 17-year-old female, which on histology was found to be a gangliocytic paraganglioma, with an extremely unusual presentation. Intraoperatively, the patient was found to have local tumor extension and regional lymph node invasion, and so she underwent a pylorus-preserving pancreaticoduodenectomy, with local lymph node clearance. We discuss the management of this unusual case and review the literature.

Use of bioelectrical impedance analysis to assess liver steatosis.

BACKGROUND: The shortage of donor livers has led to increased utilization of steatotic marginal livers. Bioelectrical impedance analysis (BIA) uses the principles of electric current flows through tissue, with less resistance offered if the water content is high and the opposite in the presence of fat. Our hypothesis was that liver steatosis would result in an increased resistance to current flow, and correlate with the degree of liver steatosis. METHODS: Before studying cadaveric donor livers for transplantation, this study was performed in patients undergoing liver resection. A total of 37 patients undergoing liver resection for cancer were analysed with BIA, using a handheld, specially calibrated Maltron BIA analyser (BioScan 915) with modified tertrapolar electrodes. These electrodes were applied to the liver surface and resistance was recorded. To validate the results of BIA, a liver biopsy was performed. Histopathology was graded quantitatively as no steatosis, mild, moderate, or severe steatosis according the percentage of fat as well as qualitatively by type of fat (micro and macrovesicular). RESULTS: Bioelectric resistance showed a correlation with macroveiscular steatosis (P = .03). CONCLUSION: BIA is a simple, noninvasive technique and its use should be explored in donor livers to assess steatosis.

Assessment of survival advantage in ampullary carcinoma in relation to tumour biology and morphology.

INTRODUCTION: Carcinoma of the ampulla of Vater is said to carry a significantly better prognosis than pancreatic ductal adenocarcinomas arising in the pancreatic head. However, it is uncertain as to whether this is due to the fact that they have differing oncological characteristics or simply an earlier presentation as a result of the exophytic morphology of ampullary lesions causing obstruction of the bile ducts. METHODS: All patients undergoing pancreaticoduodenectomy between January 1998 and December 2004 were identified from a prospectively maintained database. Patients with a pathologically confirmed ampullary (AMP) tumour were compared to those with a carcinoma of the head of the pancreas (HOP). Tumour characteristics including size, stage and degree of differentiation were analysed as were survival data. RESULTS: 71 AMP and 144 HOP tumours were resected during the period studied and had full histology reports available for assessment. The median diameter of the AMP tumours was significantly less than those of the HOP (2 cm vs. 3 cm; p = 0.04). The T stage distribution differed significantly between the AMP and HOP tumours in favour of the former (Stages I--10 vs. 0 (p = 0.03); II--29 vs. 13 (p = 0.04); III--25 vs. 121 (p = 0.01); IV--7 vs. 10). The number of resection specimens with positive lymph nodes was lower in the AMP group (31 vs. 121; p = 0.03) as was the prevalence of vascular invasion (33 vs. 114; p = 0.006) and neural invasion (23 vs. 134; p = 0.009). There was no difference in the degree of differentiation of the AMP and HOP tumours. The 5-year survival rates were significantly better in the AMP group at 60% vs. 20% (p = 0.008). Subdivision of AMP carcinoma into polypoid (60%) and ulcerating (40%) lesions revealed a non-significant survival advantage in favour of polypoid tumours at (64% vs. 60%; p = 0.07) at 5 years. CONCLUSIONS: The outcome of resection for AMP is significantly better than for pancreatic ductal adenocarcinomas arising in the periampullary region. Although the anatomical position of AMP tumours may contribute to this survival advantage, the HOP tumours exhibit more adverse histological features suggesting that they are different diseases and hence the difference in survival.

Cholangiocarcinoma complicating primary sclerosing cholangitis: a 24-year experience.

AIM: To report the prevalence and outcome of cholangiocarcinoma arising in primary sclerosing cholangitis for a British tertiary referral centre. METHODS: All patients diagnosed with primary sclerosing cholangitis and concurrent cholangiocarcinoma were identified from a prospectively maintained departmental database, and the mode of presentation, management and outcome were determined. RESULTS: Of 370 patients with primary sclerosing cholangitis, 48 patients (13%) were diagnosed with a cholangiocarcinoma within a median time of 0.51 months (range: 0-73.12) from presentation to the unit. Mode of presentation included: inoperable tumours (n = 14); incidental findings in transplant hepatectomy specimens (n = 13); primary sclerosing cholangitis follow-up (n = 9); transplant work-up (n = 5); transplant waiting list (n = 5); suspected tumour confirmed at transplant (n = 1), and incidental finding at cholecystectomy (n = 1). The diagnosis was confirmed by: radiology-guided biopsy (n = 27); MRI (n = 3); CT (n = 2); laparoscopy or laparotomy (n = 2), and frozen section at transplant (n = 1). Management consisted of: transplantation (n = 14, including 1 abandoned); hepatic resection (n = 8), and palliation through stenting (n = 26). The overall median survival of the cohort was 4.9 months (range: 0.09-104.5). Median survival ranged from 2.6 months (range: 0.09-35.3) for palliation to 7.6 months (range: 0.6-99.6) for transplantation and 52.8 months (range: 3.7-104.5) for resection. There was no difference in survival between the transplant and resection groups (p = 0.14). CONCLUSIONS: Cholangiocarcinoma is a common finding in primary sclerosing cholangitis and regular screening of this cohort of patients at referring centres is advocated to detect early tumours, as surgical treatment at an early stage offers significantly better outcomes for this cohort of patients.

Specialist outreach service for on-table repair of iatrogenic bile duct injuries--a new kind of 'travelling surgeon'.

INTRODUCTION: The objective of this study was to determine the outcome of on table repair of iatrogenic bile duct injuries (IBDIs) following laparoscopic cholecystectomy, by specialist hepatobiliary surgeons as an outreach service. PATIENTS AND METHODS: Prospectively collected data on IBDI managed as an outreach service, was analysed retrospectively. The Strasberg classification was used to define types of injury. RESULTS: There were 22 patients. Twenty (91%) had type E 'classical' excision injuries, two had types B and D. Two type E cases had co-existent vascular injury both with right hepatic artery injuries; one also had a co-existent portal vein injury. A Roux-en-Y hepaticojejunostomy was used to repair the IBDI in 21 (95%) patients. One type D injury had duct repair over a T-tube. No attempt was made to reconstruct the injured hepatic arteries, while the portal vein injury was primarily repaired. The median follow-up was 210 days (range, 47-1088 days). Two patients developed bile leak and cholangitis while another developed transient jaundice. There were no postoperative mortalities. All patients were followed up at our centre. CONCLUSIONS: Repair of IBDI as an outreach service by specialist surgeons is feasible and safe, with minimal disruption to the patient pathway. Prompt recognition and definitive management may help reduce complaints and medicolegal litigation.

Antiangiogenic therapy and surgical practice.

BACKGROUND: Antiangiogenic therapy has become a reality with the recent introduction of bevacizumab, a monoclonal antibody against vascular endothelial growth factor. METHODS: Relevant medical literature from PubMed, National Institute for Health and Clinical Excellence and National Institutes of Health websites to August 2007 was reviewed. RESULTS AND CONCLUSIONS: Although often described as the fourth modality of treatment after surgery, radiotherapy and chemotherapy, many antiangiogenic drugs have failed to live up to expectations. Nevertheless, research continues and there are reasons to believe that antiangiogenic therapy may yet have a future in the clinical setting.