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.

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.

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.

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.

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.

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.

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.

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.

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.

The microbiological impact of pre-operative biliary drainage on patients undergoing hepato-biliary-pancreatic (HPB) surgery.

BACKGROUND: The merit of pre-operative biliary drainage in managing hepatic, biliary or pancreatic patients remains unclear with previous studies demonstrating significant increases in bacterobilia. AIMS: To establish if pre-operative biliary drainage was associated with (i) a change in bacterial flora, (ii) post-operative sepsis and (iii) to ascertain if a modification of antibiotic prophylaxis was warranted. METHODS: Data were collected on 331 patients undergoing hepatic, biliary or pancreatic surgery for malignant obstruction between August 2000 and June 2005. Microbiological data from intra-operative bile, post-operative wounds, blood cultures, urine and sputum were analysed. All episodes of pre-operative endoscopic retrograde cholangiopancreatography (ERCP), stenting and percutaneous drainage were documented. RESULTS: One hundred and sixty two patients had ERCP prior to surgery and 154 had surgery only. In comparison to patients who had surgery alone stented patients had significantly increased rates of bacterobilia (40 vs. 85%) and fungobilia (8 vs. 34%, both P < 0.001). Pre-operative biliary drainage significantly increased post-operative sepsis, wound infections and prolonged in-patient stay (P < 0.05). The most common organisms cultured were coliforms and enterococcus with percutaneous transhepatic cholangiography (PTC) highly significant for the development of MRSA sepsis. CONCLUSIONS: Pre-operative biliary drainage is associated with a high incidence of bacterobilia and fungal colonization. Pre-operative biliary drainage should be utilized selectively, with modification of antibiotic prophylaxis according to patient characteristics.

Primary hepatocellular cancer in the explanted liver: outcome of transplantation and risk factors for HCC recurrence.

AIM: To evaluate the risk of recurrence of hepatocellular cancer (HCC) after liver transplantation (LT). METHODS: The clinical records of 104 patients with HCC in the explanted liver were examined. RESULTS: HCC recurrence occurred in 12 patients. Recurrence was observed in all patients with a single nodule greater than 5 cm. Among the 5 patients with more than 3 tumours with a maximum diameter of 4.5 cm, no recurrence occurred. The survival rates were 81% and 64% at 1 and 5 years, respectively; the recurrence-free survival at 1 and 5 years was, respectively, 93% and 82%. Pre-LT alpha-fetoprotein (AFP) increased at a greater magnitude in patients who experienced recurrence, compared to those who did not. Tumour diameter, differentiation, satellitosis, AFP and the magnitude of AFP increase were predictive of recurrence. The 1- and 5-year recurrence-free survival for the 68 patients who had a single nodule up to 5 cm, or up to 3 nodules all less than 4.5 cm and with a maximum cumulative diameter of 8 cm, or more than 3 nodules all less than 2.5 cm, were 95% and 92%, respectively. For the 13 patients not meeting these criteria, the 1- and 5-year recurrence-free survival was, respectively, 75% and 54% (log Rank test p=0.019). CONCLUSIONS: Patients with more than 3 small HCC nodules before LT could still have a good outcome without recurrence. A rapid increase in AFP could be useful in identifying patients with a greater risk of post-LT HCC recurrence.

Orthotopic liver transplantation for epithelioid haemangioendothelioma.

AIMS: To report seven cases of epithelioid haemangioendothelioma (EHE) of the liver, a rare, low-grade malignant neoplasm of vascular origin that have been treated in our institution. MATERIALS AND METHODS: Patients with ages ranging from 25 to 60 years presenting mainly with non-specific symptoms, such as right upper quadrant abdominal pain or weight loss. The tumours presented as multiple, nodular lesions involving both lobes of the liver. This type of tumour is often difficult to diagnose, with the final diagnosis being established only by histological examination. The key to diagnosis was the demonstration of cells containing factor VIII-related antigen. RESULTS: Five patients underwent orthotopic liver transplantation (OLT), four of whom are alive at a median follow up 38 months (11-88 months). One patient died of recurrent of disease at 88 months. Two patients did not receive an OLT since they presented with extrahepatic metastatic disease; they died at 21 and 25 months from diagnosis. CONCLUSION: Orthotopic liver transplantation may be considered as a potentially curative treatment for this rare form of tumour when the disease is confined to the liver.

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.

Diabetic control after total pancreatectomy.

BACKGROUND: Diabetes after total pancreatectomy is commonly described as 'brittle' with most series reporting outcomes after resection for pancreatitis alone. The aim of this study was to determine glycaemic control in patients resected for benign and malignant disease. METHODS: A retrospective analysis of all patients undergoing total pancreatectomy (1989-2003) from a single institution was done. Data of diabetic control were obtained from case notes, general practitioners and telephonic consultation. Comparison was made against a matched type 1 diabetic population. RESULTS: Forty-seven patients with a median age of 59 years (range 17-85 years) and median follow-up of 50 months (range 5-136 months) were identified. Thirty-five underwent primary resection with 11 receiving completion procedures. Thirty were for malignancy (19 deceased) and 17 for benign/indeterminate histology (2 deceased). Thirty-three patients were available for detailed follow-up. There was no significant difference between median HbA(1c) of the study group and the control (8.2% versus 8.1%). The majority of patients reported diabetic control and daily performance as excellent or good. Resection for pancreatitis gave poorer subjective control (p < 0.05) than those resected for malignancy. Two patients required in-patient treatment for diabetic complications, with no deaths related to diabetes observed. CONCLUSION: Diabetes after total pancreatectomy is not necessarily associated with poor glycaemic control and in the majority results in equivalent biochemical control compared to a normal type 1 diabetic population.

Marimastat as first-line therapy for patients with unresectable pancreatic cancer: a randomized trial.

PURPOSE: The prognosis for unresectable pancreatic cancer remains dismal (1-year survival rate, < 10%; 5-year survival rate, < 5%). Recent advances in conventional chemotherapy and novel molecular treatment strategies warrant investigation. This, the largest randomized study in pancreatic cancer performed to date, compares marimastat, the first of a new class of agents, with gemcitabine. PATIENTS AND METHODS: Four hundred fourteen patients with unresectable pancreatic cancer were randomized to receive marimastat 5, 10, or 25 mg bid or gemcitabine 1,000 mg/m2. The primary end point was survival. Progression-free survival, patient benefit, and safety were also assessed. RESULTS: There was no significant difference in survival between 5, 10, or 25 mg of marimastat and gemcitabine (P =.19). Median survival times were 111, 105, 125, and 167 days, respectively, and 1-year survival rates were 14%, 14%, 20%, and 19%, respectively. There was a significant difference in survival rates between patients treated with gemcitabine and marimastat 5 and 10 mg (P <.003). Both agents were well tolerated, although grade 3 or 4 toxicities were reported in 22% and 12% of the gemcitabine- and marimastat-treated patients, respectively. The major toxicity of marimastat was musculoskeletal (44% of marimastat patients, compared with 12% of gemcitabine patients; musculoskeletal toxicity was severe in only 8% of marimastat patients). CONCLUSION: The results of this study provide evidence of a dose response for marimastat in patients with advanced pancreatic cancer. The 1-year survival rate for patients receiving marimastat 25 mg was similar to that of patients receiving gemcitabine. In view of the manageable tolerability of marimastat and its ease of administration, further studies are warranted.

Surgery for hilar cholangiocarcinoma; a 10 year experience of a tertiary referral centre in the UK.

OBJECTIVE: To review the outcome of patients operated for hilar cholangiocarcinoma and analyse prognostic variables. PATIENTS AND METHODS: A prospectively collected database on patients with hilar cholangiocarcinoma, between 1992 and 2003, and relevant clinical notes were reviewed retrospectively. A total of 174 patients, 96 male, median age 63 years (27-86), were referred. Jaundice was the initial presentation in 167. RESULTS: ERCP was the initial interventional investigation at the referring centre in 150, of which only 30 were stented successfully. PTC and decompression was carried out on 120. In 17, combined PTC and ERCP were required for placement of stents. Seventy-two underwent laparotomy at which 27 had locally advanced disease. Forty-five had potentially curative resections. Extra hepatic bile duct resection was done in 14 patients of which four were R0 resections. Thirty-one had bile duct resection including partial hepatectomy with 19 R0 resections (P=0.042). Post-operative complications developed in 19 patients, and there were 4 30 day mortalities [hepatic insufficiency:/sepsis (n=3), thrombosis of the reconstructed portal vein (n=1)]. Among the patients with R0 resections, the cumulative survival rates at 1, 3, and 5 year; was 83, 58, 41%, respectively, and in those with R1 resections were 71, 24, 24%, respectively, (P=0.021). Overall survival was shorter in patients with positive perineural invasion (P=0.066: NS). There was no significant difference in survival between the node positive and negative group. Median survival of patients who underwent liver resection was longer than those with bile duct resection only (30 vs 24 months P=0.43: NS). CONCLUSIONS: ERCP was associated with a high failure rate in achieving pre-operative biliary decompression which was subsequently achieved by PTC. Clear histological margins were associated with improved survival and were better achieved by liver resection as compared to extra hepatic bile duct resection. Positive level I lymph nodes did not adversely impact survival.