Effects of transplantation-related immunosuppression on co-existent neuroendocrine tumours.

BACKGROUND: Here we detail our experience of managing patients found to have a neuroendocrine neoplasm (NEN) whilst on immunosuppression for a transplanted organ. AIM: We aimed to quantify the behaviour of NENs under solid-organ transplant-related immunosuppression. DESIGN: This was an observational, retrospective case series. METHODS: Ten patients were identified from a prospectively kept database. Three were excluded. RESULTS: Four patients received a liver, two a kidney, and one a heart transplant. All but one received calcineurin-based immunosuppression. NENs were found in five patients post-transplant: one had surgery for transverse colonic neuroendocrine carcinoma NEC (pT4N1M0, Ki67 60%), was cancer-free after four years; one had cold biopsy of duodenal NEN (pT1N0M0, Ki67 2%), cancer-free at four months; one 7 mm pancreatic NEN (pT1N0M0), untreated and stable for seven years; one small-bowel NEN with mesenteric metastasis (pTxNxM1), alive four years after diagnosis; and one untreated small-bowel NEN with mesenteric metastasis, stable at 1 year after liver transplantation. Two NENs were discovered pre-transplant, one pancreatic NEN (pT1N0M0, Ki67 5%), remains untreated and stable at three years. One gastric NEN (type 3, pT1bN0M0, Ki67 2%) remains stable without treatment for two years. CONCLUSIONS: NENs demonstrate indolent behaviour in the presence of transplant-related immunosuppression.

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 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.

Outcome following Resection of Biliary Cystadenoma: A Single Centre Experience and Literature Review.

Background. Biliary cystadenomas (BCAs) are rare, benign, potentially malignant cystic lesions of the liver, accounting for less than 5% of cystic liver tumours. We report the outcome following resection of biliary cystadenoma from a single tertiary centre. Methods. Data of patients who had resection of BCA between January 1993 and July 2014 were obtained from liver surgical database. Patient demographics, clinicopathological characteristics, operative data, and postoperative outcome were analysed. Results. 29 patients had surgery for BCA. Male : female ratio was 1 : 28. Clinical presentation was abdominal pain (74%), jaundice (20%), abdominal mass (14%), and deranged liver function tests (3%). Cyst characteristics included septations (48%), wall thickening (31%), wall irregularity (38%), papillary projections (10%), and mural nodule (3%). Surgical procedures included atypical liver resection (52%), left hemihepatectomy (34%), right hemihepatectomy (10%), and left lateral segmentectomy (3%). Median length of stay was 7 (IQ 6.5-8.5) days. Two patients developed postoperative bile leak. No patients had malignancy on final histology. Median follow-up was 13 (IQ 6.5-15.7) years. One patient developed delayed biliary stricture and one died of cholangiocarcinoma 11 years later. Conclusion. Biliary cystadenomas can be resected safely with significantly low morbidity. Malignant transformation and recurrence are rare. Complete surgical resection provides a cure.

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.

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.

Effect of preoperative chemotherapy on liver resection for colorectal liver metastases.

AIM: To compare the effects of preoperative chemotherapy on liver parenchyma morphology, as well as morbidity and mortality after liver resection for colorectal liver metastases. METHODS: Prospectively collected data on 173 patients undergoing liver resection for CLM between 1/2003 and 9/2005 was analysed in three groups: A: preoperative oxaliplatin (Ox, n=70); B: other chemotherapeutic agents (OC, n=60); and C: surgery alone without chemotherapy (SA, n=43). Blood transfusion, hospital stay, operative procedure, peak postoperative bilirubin levels, complications and histopathology of the resected liver were compared. RESULTS: Intra-operative blood transfusion requirement (34%) and biliary complications (16%) was higher in patients receiving oxaliplatin-based chemotherapy (p=0.01 and p=0.06, respectively). Oxaliplatin-based chemotherapy was also associated with sinusoidal dilatation of mild grade in 52.8% vs. 26.6% and 23.3% patients (p=0.007 and p=0.004) in other groups, respectively. Steatosis was similarly distributed across the study group. Postoperative mortality was 2, 1 and 4 patients, respectively (p=ns). CONCLUSION: Oxaliplatin-based preoperative chemotherapy is associated with vascular alterations in the liver parenchyma without significantly increasing the risk of steatosis, or postoperative morbidity and mortality.

Haemorrhage following pancreaticoduodenectomy: risk factors and the importance of sentinel bleed.

AIM: To document the prevalence and to evaluate the management strategies of haemorrhagic complications following pancreaticoduodenectomy (PD). METHODS: All patients who underwent PD from 1/2000 to 10/2005 and experienced at least one episode of haemorrhage during the 30 first days postoperatively were recorded. Etiology of haemorrhage, treatment strategy and mortality rate were recorded and analyzed. RESULTS: A total of 362 patients underwent PD during this period and 32 (8.8%) had haemorrhage postoperatively of whom 15 died (47% mortality rate). Primary intraluminal haemorrhage was recorded in 13 patients, primary intra-abdominal haemorrhage in 5 patients and secondary haemorrhage in 14 patients. Successful management of haemorrhage with angioembilization occurred in 2 patients in the study group. Statistical analysis revealed sepsis and sentinel bleed as risk factors for post-PD haemorrhage and pancreatic leak and sentinel bleed as risk factors for secondary haemorrhage (p < 0.05). CONCLUSIONS: Haemorrhage after PD is a life-threatening complication. Sepsis, pancreatic leak, and sentinel bleed are statistical significant factors predicting post-PD haemorrhage. Sentinel bleed is not statistically significant associated with postoperative mortality, but with the onset of secondary haemorrhage. The effectiveness of therapeutic angioembolization was not demonstrated in our study.

Results of vascular resections during pancreatectomy from two European centres: an analysis of survival and disease-free survival explicative factors.

OBJECTIVES: The object of our study was to report on the experience with vascular resections at pancreatectomy in two European specialist hepatopancreatobiliary centres and evaluate outcome and prognostic factors. PATIENTS AND METHODS: From 1989 to 2002, 45 patients (21 men, 24 women) underwent pancreatectomy for a pancreatic mass: Whipple's procedure (n=33), total pancreatectomy (n=10) or left splenopancreatectomy (n=2), along with a vascular resection, i.e. venous (n=39), arterial (n=1) or venous + arterial (n=5). RESULTS: Operative mortality was nil, postoperative mortality was 2.2% (n=1); 34 patients had an uneventful postoperative course. Reoperations were performed for portal vein thrombosis (n=1), pancreatic leak (n=1), gastric outlet syndrome (n=1) and gastrointestinal bleeding (n=1). In all, 43 patients had cancer on pathology examination, with retropancreatic invasion in 72% and lymph node extension in 62.8%. Resection was R0 in 21 cases. Vessel wall invasion was present in 13 cases and 19 had perivascular invasion. Disease-free survival (DFS) at 1, 2 and 3 years was 36.0%, 15.0% and 12.0%, respectively. Median DFS length was 8.7 months (95% CI: 7.2; 10.2). Overall survival rates were 56.6%, 28.9% and 19.2%, respectively. Median survival length was 14.2 months (95% CI: 9.8; 18.6). A multivariate analysis of prognostic variables identified tumour location (other than head of pancreas), neoadjuvant chemotherapy and advanced disease stage as adverse factors for DFS. CONCLUSION: Survival and DFS rates of these patients are comparable to those without vascular resection. Tumour localization, tumour stage, neoadjuvant treatment and tumour recurrence are explanatory variables of survival. Tumour localization, tumour stage and neoadjuvant treatment were explanatory variables for DFS. However, the type and extent of vascular resections as well as vessel wall invasion does not affect survival and DFS.

Neuroendocrine tumours of the pancreas: predictors of survival after surgical treatment.

AIMS: Neuroendocrine tumours of pancreatic and duodenal origin (NETP) are rare and we present a significant experience from a single centre. METHODS: Data was collected on 44 patients who underwent surgery between 1988 and 2002. Since 1997, data have been recorded prospectively on a dedicated database. RESULTS: Twenty-four patients had functioning tumours (16 insulinomas, 3 gastrinomas, 2 somatostatinomas, 1 vipoma, 1 glucagonoma and 1 carcinoid tumour). Nine functioning tumours and 13 non-functioning had a malignant phenotype. Twenty pancreaticoduodenectomies, 9 local excisions, 7 distal and 2 total pancreatectomies, 5 bypasses and 1 exploratory laparotomy were performed. Fourteen patients (31.8%) had surgical complications, 1 died peri-operatively (2.3%). The overall actuarial survival for resected cases was 74.4 and 42.5% at 5 and 10 years, respectively. Lymph node invasion and metastases were significant predictors of survival by univariate analysis and only the presence of metastases retained significance on multivariate analysis. CONCLUSION: Surgical resection is the only curative treatment for NETP. Resection can be safely carried out in a specialist centre and is associated with good long-term survival. The presence of metastases was a significant predictive factor for survival in patients with NEPT in this series.

Favourable prognostic factors in a large UK experience of adenocarcinoma of the head of the pancreas and periampullary region.

AIMS: To present the surgical experience in a regional unit, analysing the post-operative outcome, and determining risk factors for survival after pancreaticoduodenectomy for periampullary and pancreatic head carcinoma. METHODS: Data were collected on 251 patients with pancreatic head adenocarcinoma (133), ampullary carcinomas (88) and distal common bile duct (30), between 1987 and 2002. Survival was calculated using the Kaplan-Meier method. Clinical, surgical and histopathological records were examined by univariate and multivariate analysis to identify the independent prognostic predictors of survival. RESULTS: Median actuarial survival for carcinoma of the pancreatic head, ampulla and distal bile duct were 13.4, 35.5 and 16 months, respectively; p < 0.0001. On univariate analysis for the whole series, the age < or =60, tumour of the head of the pancreas, lymph node positive, resection margin R1, poorly differentiated tumours, and portal vein invasion significantly decreased survival. On multivariate analysis, poor tumour differentiation, surgical margin, lymph node metastases, and age independently influence survival. Mortality and morbidity were 4.8 and 29.9%, respectively. CONCLUSIONS: Pancreaticoduodenectomy for pancreatic and periampullary tumours is the only therapy that may cure patients and can be performed safely in centres with significant experience.

Liver resection for colorectal metastases.

BACKGROUND: Colorectal cancer is the second commonest malignancy in the UK. Metastases to the liver occur in greater than 50% of patients and remain the biggest determinant of outcome in these patients. Liver resection is a safe procedure that achieves good long-term survival, but surgery has traditionally been limited to select groups of patients. The improved outcome suggests that more patients could benefit from resection if more was known of what criteria are predictive of a good outcome. PATIENTS AND METHODS: A retrospective analysis was performed on all patients undergoing surgical resection of the liver for colorectal metastases between March 1989 and March 2001 in the Birmingham Liver Unit. RESULTS: During this period, 212 liver resections for colorectal cancer metastases were performed in 82 females and 130 males. The median follow-up was 16 months with an overall actuarial survival of 86% at 1 year, 54% at 3 years, and 28% at 5 years. The peri-operative mortality was 2.8%. The number and timing (metachronous or synchronous) of metastatic lesions, the gender of the patient, pathological staging of the primary lesion or surgical resection margins had no significant influence on survival. Patients with lesions less than 5 cm in size had a significantly prolonged survival compared with patients with lesions greater than 5 cm in size (P < 0.004). CONCLUSIONS: Liver resection is the only curative treatment for patients with colorectal metastases. The long-term survival reported in patients with resected colorectal metastases confined to the liver is comparable to primary surgery for solid gastrointestinal tumours. Every attempt must be made to increase the availability of liver resection to patients with hepatic metastases from colorectal cancer.

Prospective validation of a standardized questionnaire for estimating childhood mortality and morbidity due to pneumonia and diarrhoea.

This paper reports the validation of a 'best-judgement' standardised questionnaire using guidelines and algorithms developed by an expert working group conducted in Nicaragua between 1995 and 1997. Prospective hospital data, including standardised medical recording of selected signs and symptoms, laboratory and radiographic test results and physician diagnoses were collected for children < 5 years admitted with any serious life-threatening condition in 3 study hospitals. The mothers or caregivers of the children were later traced and interviewed using the 'best-judgement' questionnaire. Interviews were completed 1-22 months after admission to hospital for 1115 children (400 who died during the stay in hospital and 715 who were discharged alive). The cause of death or admission to hospital was determined by an expert algorithm applied to hospital data. A similar procedure was used to derive the cause using the answers to questions from interviews. Hospital causes were compared with interview causes and sensitivity and specificity calculated, together with the estimated cause-specific fraction for diarrhoea and pneumonia. Multiple diagnoses were allowed; 378 children in the sample (104 deaths, 274 survivors) had a reference diagnosis of diarrhoeal illness, and 506 (168 deaths, 338 survivors) a reference diagnosis of pneumonia. When results for deaths and survivors in all age groups were combined, the expert algorithms had sensitivity between 86% and 88% and specificity between 81% and 83% for any diarrhoeal illness; and sensitivity between 74% and 87% and specificity between 37% and 72% for pneumonia. Algorithms tested in previous validation studies were also applied to data obtained in this study, and the results are compared. Despite less than perfect sensitivity and specificity, reasonably accurate estimates of the cause-specific mortality and morbidity fractions for diarrhoea were obtained, although the accuracy of estimates in other settings using the same instrument will depend on the true cause-specific fraction in those settings. The algorithms tested for pneumonia did not produce accurate estimates of the cause-specific fraction, and are not recommended for use in community settings.

Does intelligence account for the link between maternal literacy and child survival?

The strong and consistent correlation between maternal education and child health is now well known, and numerous studies have shown that wealth and income cannot explain the link. Policy-makers have therefore assumed that the relationship is causal and explicitly advocate schooling as a child health intervention. However, there are other factors which could account for the apparent effect of maternal education on child morbidity and mortality, one of which is intelligence. This paper examines the effect of maternal intelligence on child health and looks at the degree to which it can explain the literacy associations with child survival and risk of malnutrition. The data are from a retrospective cohort study of 1294 mothers and their 7475 offspring, of whom 454 were women who had learned to read and write as adults in Nicaragua's literacy programme, 457 were illiterate, and 383 had become literate as young girls attending school. The women's intelligence was tested using Raven's Coloured Progressive Matrices. Acquisition of literacy was strongly related to intelligence. Statistically significant associations with maternal literacy were found for under five mortality, infant mortality, and the risk of low mid-upper-arm circumference (MUAC) for age, before and after controlling for a wide range of socio-economic factors. Under five, child (one to four years), infant and post-neonatal mortality plus the risk of low height for age were significantly correlated with intelligence, but only with infant and under mortality rates did the association remain significant after controlling for socio-economic factors. A significant interaction between intelligence and literacy for under five mortality was due to literacy having a strong effect in the women of low intelligence, and a negligible effect among those of high intelligence. This study provides evidence that intelligence is an important determinant of child health among the illiterate, and that education may have the greatest impact on child health for mothers of relatively low intelligence.