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.

Influence of propionic acid on growth and aflatoxin production by Aspergillus flavus in liquid submerged and solid substrate conditions.

The present experiments demonstrate that sublethal concentrations of propionic acid stimulated aflatoxin production considerably in submerged shaken culture and solid substrate culture of Aspergillus flavus. In liquid conditions aflatoxin formation was significantly influenced by the time of addition of propionic acid. The spores initially swelled into large spherical cells, and the resultant hyphae developed into a swollen, stunted, and excessively branched mycelium.

Long-term clinical investigation of the hepatobiliary agents: 99mTc-HIDA and 99mTc-p-butyl-IDA.

The organ distribution data for the two hepatobiliary agents HIDA and p-butyl-IDA in mice showed substantial differences in the extent and rate of hepatobiliary clearance of radioactivity. 99mTc-HIDA and 99mTc-p-butyl-IDA were used in computer assisted serial hepatobiliary scintigraphy. In normal subjects, the data of dynamic studies showed that the kidneys were no longer seen after 2.5 min with p-butyl-IDA. Liver radioactivity decreased significantly after 10 min with HIDA compared to 35 min with p-butyl-IDA. The gall bladder was always visualized at the 10-12th min and the 25-30th min with HIDA and p-butyl-IDA respectively. 99mTc-HIDA provided superior hepatic duct images.

Preparation and biokinetic studies of 99mTc-p-butyl-IDA for hepatobiliary scintigraphy.

A freeze-dried powder of tin-p-butyl-IDA to be labelled with 99mTc for hepatobiliary scintigraphy has been developed. Gel chromatography column scanning has been applied for evaluating the labeling efficiency of the complex under different conditions. The results of organ distribution studies in mice and of clinical investigations in human beings showed the stability of the radiopharmaceutical. The preparative 99mTc-p-butyl-IDA concentrates moderately well in the bile with a rapid blood clearance into hepatocytes, very low excretion in the urine and slow clearance into the bile.

Application of sodium stannite in the preparation of instant [99mTc]HIDA kit.

A rapid method for the production of freeze-dried kit containing 20 mg HIDA and 0.4 mg SnCl2 X 2H2O at pH 5.5-6.0 was developed using the stannite procedure. The Sn-HIDA ligand has been prepared successfully by dissolving HIDA in stannite solution without further pH adjustment. A gelchromatography column scanning (GCS) technique has been applied to study the chemical state of technetium in the preparation. The shelf-life of the freeze-dried powder of Sn-HIDA was found stable for at least 6 months as assessed by the GCS-technique. The hepatobiliary agent has a rapid blood clearance and is excreted predominantly by the hepatobiliary system. The biodistribution study in mice showed that more than 30% of the injected dose has been accumulated in liver at 5 min postinjection and at 30 min most of the injected activity has been passed to the intestine via the biliary system.

Ytterbium-169-phytate: a potential new radiopharmaceutical for functional scintigraphy of the liver.

A new radiopharmaceutical for liver scintigraphy has been prepared by reacting 169YbOCl with Na phytate under conditions which yield a labelling efficiency of more than 99% over a wide pH range. In rabbits the resultant colloidal preparation shows a rapid elimination from the blood and high initial uptake in liver. Subsequently about 90% of the liver activity is lost within 3 days, the remainder being eliminated more slowly. The radiopharmaceutical is non-toxic and has a shelf-life of about 3 months. Scintigrams obtained in patients with hepatomegaly suggest that this new agent gives better visualization of space occupying lesions of the liver than 99mTc-Sn colloid. The radiation dose to the patient from this agent is low and comparable with that from other radiopharmaceuticals used for liver scintigraphy.

99mTc-labelled Cu(I)-EHDP, a potential skeletal imaging agent.

99mTc-Cu-EHDP has been prepared with high labelling yield applying for the first time the method of instantly formed cuprous ions in the mixture. A gel chromatography column scanning technique has been used to study the 99mTc fractions in the preparation. The study of the influence of pH-value on the amount of 99mTc-CU-EHDP fraction shows that pH 1.6 - 1.7 gave the best labelling results. The formation rate of 99mTc-Cu-EHDP complex with a high labelling yield was fast and achieved within a few mins. This suggests the reduction of 99mTc-pertechnetate to Tc (IV). The final preparation was found stable for at least 4 hrs after mixing the reactants with the 99mTc-eluate. Comparative biokinetic studies of 99mTc-Cu-EHDP and 99mTc-Sn-EHDP in rabbits and mice showed a high bone uptake and fast elimination of 99mTc-Cu-EHDP from the skeleton. No significant difference was found in the plasma protein binding of 99mTc-Cu-EHDP and 99mTc-Sn-EHDP in rats as assessed by the GCS-technique. Radionuclide imaging in rabbits, using a gamma camera, showed 99mTc-Cu-EHDP to be a good bone-imaging agent.