Pancreaticoduodenectomy with preoperative total embolization of the hepatic arteries (PD-HAE)-a novel treatment with sacrifice of the hepatic arterial blood supply without the need for arterial reconstruction.

PURPOSE: Tumors with involvement of common hepatic and gastroduodenal arteries (CHA and GDA) or GDA and the proper hepatic artery (PHA) are traditionally considered nonresectable. We have devised a new procedure that includes pancreaticoduodenectomy with preoperative hepatic artery embolization (PD-HAE) to facilitate an R0 resection of tumors involving the hepatic arteries without vascular anastomoses and complete sacrifice of normal hepatic arterial blood supply. METHODS: To allow resection of the hepatic arteries, preoperative embolization of the PHA was performed to induce an increased collateral arterial blood flow from the periphery of the liver, far from the hepatic hilum 10-14 days prior to the operation. Between May 1, 2017 and December 31, 2019, eight patients with ductal adenocarcinoma were operated with the PD-HAE procedure. RESULTS: The embolizations were uneventful apart from a transient marginal elevation of alanine aminotransferase in three patients. All patients had N disease with perineural invasion of tumor cells around the adventitia of the artery and severe perivascular inflammation. An R0 resection (> 1.0 mm to all resection margins) was obtained in six patients (75%). Mean hospital stay was 12 days. Median survival was 23 months (95% CI: 19.5-26.5 months). Six patients (75%) are still alive 11 to 36 months after the operation. There was perioperative fatality, and morbidity was comparable to standard pancreaticoduodenectomy. CONCLUSION: PD-HAE is a safe procedure and may provide the opportunity for curative resection in otherwise unresectable patients. However, larger studies are needed to evaluate this procedure.

Genomic alterations accompanying tumour evolution in colorectal cancer: tracking the differences between primary tumours and synchronous liver metastases by whole-exome sequencing.

BACKGROUND: Colorectal cancer (CRC) patients with metastatic disease can become cured if neoadjuvant treatment can enable a resection. The search for predictive biomarkers is often performed on primary tumours tissue. In order to assess the effectiveness of tailored treatment in regard to the primary tumour the differences in the genomic profile needs to be clarified. METHODS: Fresh-frozen tissue from primary tumours, synchronous liver metastases and adjacent normal liver was collected from 21 patients and analysed by whole-exome sequencing on the Illumina HiSeq 2500 platform. Gene variants designated as 'damaging' or 'potentially damaging' by Ingenuity software were used for the subsequent comparative analysis. BAM files were used as the input for the analysis of CNAs using NEXUS software. RESULTS: Shared mutations between the primary tumours and the synchronous liver metastases varied from 50 to 96%. Mutations in APC, KRAS, NRAS, TP53 or BRAF were concordant between the primary tumours and the metastases. Among the private mutations were well-known driver genes such as PIK3CA and SMAD4. The number of mutations was significantly higher in patients with right- compared to left-sided tumours (102 vs. 66, p = 0.004). Furthermore, right- compared to left-sided tumours had a significantly higher frequency of private mutations (p = 0.023). Similarly, CNAs differed between the primary tumours and the metastases. The difference was mostly comprised of numerical and segmental aberrations. However, novel CNAs were rarely observed in specific CRC-relevant genes. CONCLUSION: The examined primary colorectal tumours and synchronous liver metastases had multiple private mutations, indicating a high degree of inter-tumour heterogeneity in the individual patient. Moreover, the acquirement of novel CNAs from primary tumours to metastases substantiates the need for genomic profiling of metastases in order to tailor metastatic CRC therapies. As for the mutational status of the KRAS, NRAS and BRAF genes, no discordance was observed between the primary tumours and the metastases.

Evaluation of a fast-track programme for patients undergoing liver resection.

BACKGROUND: Recent developments in perioperative pathophysiology and care have documented evidence-based, multimodal rehabilitation (fast-track) to hasten recovery and to decrease morbidity and hospital stay for several major surgical procedures. The aim of this study was to investigate the effect of introducing fast-track principles for perioperative care in unselected patients undergoing open or laparoscopic liver resection. METHODS: This was a prospective study involving the first 100 consecutive patients who followed fast-track principles for liver resection. Catheters and drains were systematically removed early, and patients were mobilized and started eating and drinking from the day of surgery. An opioid-sparing multimodal pain treatment was given for the first week. Discharge criteria were: pain sufficiently controlled by oral analgesics alone, patient comfortable with discharge and no untreated complications. RESULTS: Median length of stay (LOS) for all patients was 5 days, with 2 days after laparoscopic versus 5 days following open resection (P < 0·001). Median LOS after minor open resections (fewer than 3 segments) was 5 days versus 6 days for major resections (3 or more segments) (P < 0·001). Simple right or left hemihepatectomies had a median LOS of 5 days. The readmission rate was 6·0 per cent and 30-day mortality was zero. CONCLUSION: Fast-track principles for perioperative care were introduced successfully and are safe after liver resection. Routine discharge 2 days after laparoscopic resection and 4-5 days after open liver resection may be feasible.

Preoperative high-dose glucocorticoids for early recovery after liver resection: randomized double-blinded trial.

BACKGROUND: Glucocorticoids modulate the surgical stress response. Previous studies showed that high-dose preoperative glucocorticoids reduce levels of postoperative inflammatory markers and specific biomarkers of liver damage compared with placebo, and suggested a reduced complication rate and shorter hospital stay after liver surgery. However, there are no studies with a clinical primary outcome or of early recovery outcomes. The aim of this study was to investigate whether a single high dose of preoperative glucocorticoid reduces complications in the immediate postoperative phase after liver surgery. METHODS: This was a single-centre, double-blinded, parallel-group RCT investigating preoperative methylprednisolone 10 mg/kg (high dose) versus dexamethasone 8 mg (standard-dose postoperative nausea prophylaxis) in patients scheduled for open liver resection. The primary outcome was number of patients with a complication in the postanaesthesia care unit; secondary outcomes included duration of hospital stay, pain and nausea during admission, and 30-day morbidity. RESULTS: A total of 174 patients (88 in high-dose group, 86 in standard-dose group) were randomized and analysed (mean(s.d.) age 65(12) years, 67.2 per cent men); 31.6 per cent had no serious co-morbidities and 25.3 per cent underwent major liver resection. Complications occurred in the postanaesthesia care unit in 51 patients (58 per cent) in the high-dose group and 58 (67 per cent) in the standard-dose group (risk ratio 0.86, 95 per cent c.i. 0.68 to 1.08; P = 0.213). Median duration of hospital stay was 4 days in both groups (P = 0.160). Thirty-day morbidity and mortality rates were similar in the two groups. CONCLUSION: A high dose of preoperative glucocorticoids did not reduce acute postoperative complications after open liver resection compared with a standard dose. Registration number: NCT03403517 (http://www.clinicaltrials.gov); EudraCT 2017-002652-81 (https://eudract.ema.europa.eu/).

Oxidative DNA damage after transplantation of the liver and small intestine in pigs.

Oxidative damage is thought to play an important role in ischemia/reperfusion injury, including the outcome of transplantation of the liver and intestine. We have investigated oxidative DNA damage after combined transplantation of the liver and small intestine in 5 pigs. DNA damage was estimated from the urinary excretion of the repair product 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG). In the first 1-3 hr after reperfusion of the grafts, 8-oxodG excretion was increased 2.9-fold (1.7-4.1; 95% confidence intervals; P < 0.05). A control experiment included sham surgery with clamping of the suprarenal inferior caval vein in 2 pigs during steady state infusion of 8-oxodG. While the caval vein was clamped, the urinary excretion of 8-oxodG was almost blocked, whereas after removal of the clamp, the excretion returned to and did not exceed the preclamp levels. In a separate experiment with 2 pigs, the elimination of injected 8-oxodG was shown to adhere to first-order kinetics with a clearance and a terminal elimination half-life of approximately 4 ml min-1 kg-1 and 2 1/2 hr, respectively. The injected dose was completely excreted into the urine within 4 hr. It is concluded that substantial oxidative damage to DNA results from reperfusion of transplanted small intestine and liver in pigs, as estimated from the readily excreted repair product 8-oxodG.

[Partial orthotopic liver transplantation]. / Partiel ortotopisk levertransplantation.

From October 1990 to May 1992, nine of 38 patients with liver transplants (24%) had partial orthotopic liver transplantation on account of lack of size-matching donor livers. The preliminary results have presented very few problems; there was no per- or postoperative mortality and no surgical complications. Four patients had episodes of acute rejection which responded to anti-rejection therapy, and two patients were treated for CMV infection. All patients are discharged with normal liver function 4-9 weeks after transplantation (median 5 weeks). The method seems to be safe and can be used in centers with limited activity, where there is a problem of having the correct liver at the correct time.

An in vitro characterization of a silicone tonometer system for synchronous measurement of tissue oxygen- and carbon dioxide tension.

A new tonometry system for continuous and synchronous measurement of tissue oxygen- and carbon dioxide tension is described and characterized in vitro. The tonometer system consists of an O2 and CO2 permeable silicone tube continuously flushed with isotonic saline by an injection pump. When the saline passes through the tonometer tube it equilibrates with O2 and CO2 outside the tube. The oxygen- and carbon dioxide tension of the flushing solution after passage of the tonometer tube are measured by a transcutaneous combined oxygen/carbon dioxide electrode (E5280 Radiometer A/S, Copenhagen, Denmark), connected to the tonometer tube via an airtight polycarbonate chamber. In order to characterize the tonometer system in vitro the tonometer tube was submerged in a test chamber containing isotonic saline, 33 degrees C to 41 degrees C, with varying partial pressures of O2 and CO2. For various lengths of the tonometer and flushing rates through the tonometer the partial pressures of oxygen and carbon dioxide in the flushing solution (pO2eq and pCO2eq), after passage through the tonometer were recorded and compared to the known partial pressures of oxygen and carbon dioxide in the test chamber solution (pO2 test and pCO2test). PO2eq and pCO2eq approached pO2test and pCO2test, when the length of the tonometer was increased, and the flushing rate through the tonometer was decreased. The relative differences (D) between pO2eq and pCO2eq at the one hand and pO2test and pCO2test at the other hand were calculated, and equilibration curves were constructed.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterization of the silicone tonometer using a membrane-covered transcutaneous electrode.

A new oxygen tonometry system consisting of a silicone tube, highly permeable to O2 and CO2 is described. The silicone tube was connected to a membrane-covered transcutaneous oxygen electrode (E5242 Radiometer A/S, Copenhagen, Denmark) via an airtight polycarbonate chamber, and flushed with isotonic saline equilibrated with atmospheric air. The present tonometer system offers certain advantages compared with other systems: continuous reading, minimal oxygen consumption, furthermore the system is thermostated and is insensitive to movement. The tonometry system was tested in vitro for characterization of a silicone tube (Coroplast, Fritz Müller KG, Wuppertal, FRG) 1.0 mm in inner diameter and 1.5 mm in outer diameter. The experiments showed that the oxygen tension measured at the electrode after passage of the tonometer approached the oxygen tension outside the tonometer when the length of the tonometer was increased and when the flushing rate of saline through the tonometer was decreased. The time taken for the flushing solution to reach an equilibrium with the oxygen tension outside the tonometer increased with increasing tonometer length, and decreased with increasing flushing rate. Changing the difference between oxygen partial pressure in the flushing solution and the oxygen partial pressure outside the tonometer tube did not influence the relative equilibration value and the equilibration time. When a pO2 value is measured by the electrode, the exact oxygen tension outside the tonometer tube, for every given length of the tonometer and flushing rate through the tonometer can be read from our calibration curves.