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.

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/).

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.

Subcutaneous oxygen and carbon dioxide tensions during head-up tilt-induced central hypovolaemia in humans.

The effect of hypovolaemic shock on subcutaneous oxygen and carbon dioxide tensions was studied in man. Subcutaneous oxygen (Psc,O2) and carbon dioxide (Psc,CO2) tensions were monitored, during 50 degrees head-up tilt (anti-Trendelenburg's position)-induced central hypovolaemia, in two females and eight males, using a silicone tonometer on the lateral upper aspect of the right arm. All cardiovascular variables remained stable at rest. Incremental tilting to 50 degrees increased heart rate (HR) and mean arterial pressure (MAP) (p < 0.01), while stroke volume (SV), cardiac output (CO) and central venous saturation (SvO2) decreased (p < 0.05). Presyncopal symptoms appeared after 28 (8-48) min (mean and range) as HR decreased from 82 (63-108) to 52 (36-70) beats min-1 (p < 0.05), MAP from 88 (61-106) to 46 (37-54) mmHg and SvO2 from 0.68 (0.56-0.76) to 0.58 (0.39-0.70) (p < 0.01). On return of the tilt table to the horizontal position HR, MAP, SV, CO and SvO2 immediately re-established resting values. The Psc,O2 was 83 (72-102) mmHg at rest and during tilting it increased to 89 (82-111) mmHg followed by a decrease to 72 (58-97) mmHg (p < 0.01) at the appearance of presyncopal symptoms. Psc,O2 returned to the pretilt level over 45 (30-60) min of recovery. Arterial oxygen, carbon dioxide and Psc,CO2 did not change significantly. Subcutaneous oxygen tension decreases during marked central hypovolaemia and it returns slowly to the resting level during recovery. Psc,O2 is a more sensitive marker of impaired tissue oxygenation than arterial oxygen pressure.

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.

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)

[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.

Ceftriaxone/metronidazole is more effective than ampicillin/netilmicin/metronidazole in the treatment of bacterial peritonitis.

In a prospective, open, controlled clinical study, 190 consecutive patients who were thought to have bacterial peritonitis before operation, were randomised to antibiotic treatment during and after operation with either ceftriaxone 1 g plus metronidazole 1.5 g once daily (n = 94) or ampicillin 2 g plus netilmicin 150 mg twice daily plus metronidazole 1.5 g once daily (n = 96). Incisional and deep surgical wound infections, postoperative pneumonia and urinary tract infection as well as deaths caused by infection were recorded. Ceftriaxone-metronidazole was significantly more effective than ampicillin-netilmicin-metronidazole, 6/94 wound related infections (6%) compared to 18/96 (19%) (p = 0.02). In patients with peritonitis caused by a perforated colon or appendix the rates of clinical failure were 6% and 28%, respectively. We consider ceftriaxone plus metronidazole an efficient and easily administered antibiotic regimen in patients with bacterial peritonitis, and both the wide range of activity against Gram-negative aerobic rods and the long half life of ceftriaxone seem to be beneficial.

Gastric and colonic oxygen tension measured with a vacuum-fixed oxygen electrode.

A new electrode system for determination of visceral oxygen tension is presented. The system consists of a transcutaneous oxygen electrode (E5242 Radiometer A/S. Copenhagen), which is screwed into a suction ring and fixed to the organ by applying a vacuum. The electrode membrane is then in contact with the organ surface via a fluid layer with a thickness of a few micrometres, without interference from atmospheric air and without mechanical disturbance of the membrane. The electrode system was tested on the gastric and colonic wall in six pigs. As reference, a silicone tonometer was placed subserously beneath the vacuum-fixed electrode. The silicone tonometer was connected to a second transcutaneous oxygen electrode. The tissue oxygen tension was changed by subjecting the animals to various inspiratory concentrations of oxygen and to hypovolaemia. The oxygen tension measured by the vacuum-fixed electrode (PO2vac) was compared with the oxygen tension measured by the tonometer (PO2tono). A good correlation was demonstrated between PO2vac and PO2tono, the correlation coefficient being 0.8619, confirming that the suction-fixed oxygen electrode measures tissue oxygen. The lowest possible vacuum to hold the electrode unit in place was between 4.0 and 6.7 kPa. Provided the measuring time did not exceed 3 min. vacuum had only slight influence on the measured oxygen values. The mean change in PO2vac induced by varying the vacuum from 7 to 26 kPa, and 26 to 7 kPa, was only +0.23 kPa (-1.2 to +1.9) and +0.19 kPa (-0.3 to +1.3), respectively. The mean stabilization time, defined as the time from electrode application until achieving 95% of the equilibration value, was 66 sec (SEM, 3.4 sec) and 57 sec (SEM, 3.0 sec) on the gastric and colonic wall, respectively. The measured values of PO2vac varied significantly between different areas on the gastric wall (p less than 0.001). When several surface measurements were performed throughout the investigated area, the mean oxygen tension approached the oxygen tension measured by the tonometer. It is concluded that the vacuum-fixed electrode constitutes a reliable, easy and, noninvasive method for measurements of the oxygen tension in the gastric and colonic tissue.

Ceftriaxone vs. ampicillin + metronidazole as prophylaxis against infections after clean-contaminated abdominal surgery.

In a prospective, controlled, double-blind study, 496 patients undergoing abdominal surgery were given antibiotic prophylaxis with a single dose of either ceftriaxone or ampicillin + metronidazole. No significant intergroup difference was found between the respective overall rates of infectious complications (3.2% and 4.9%). Analysis of the microbiologic findings showed incisional wound infections, mainly caused by gram-negative rods, to be more common in the ampicillin-metronidazole group, whereas deep wound infections were more frequent in the ceftriaxone group. It is concluded that ceftriaxone seems to be more efficient than ampicillin-metronidazole as prophylaxis against incisional wound infection, but should preferably be supplemented with an antianaerobic agent to prevent deep wound infections.

Continuous assessment of oxygen saturation and subcutaneous oxygen tension after abdominal operations.

Ten patients undergoing abdominal operations had oxygen saturation (SpO2) and transcutaneous (PtcO2) and subcutaneous (PscO2) oxygen tensions monitored continuously during the second and third postoperative nights from 11 pm to 7 am. At the end of the second postoperative night an oxygen stimulation test (10 l/min by face mask) was carried out in eight of the 10. Median SpO2 was 91% (range 82-95) on the second, and 91% (86-95) on the third, postoperative nights, respectively. Six patients had intermittent episodes of desaturation to less than 80%, each of less than one minute's duration. PtcO2, but not PscO2, followed the episodic variations in SpO2. PscO2 was 58 mmHg (46-69) on the second postoperative night and 61 mmHg (48-71) on the third postoperative night. PscO2 correlated with SpO2 in all but one patient who had lower PscO2 than expected from the measured SpO2 and estimated PaO2. Oxygen treatment increased individual PscO2 by 14 mmHg (9-49), PtcO2 by 38 mmHg (10-104), and SpO2 to 99% (95-100), but stable PscO2 was not achieved within the 20 minute period of treatment. These results obtained during continuous measurements show pronounced intersubject differences in oxygen tensions near the surgical wound in the late postoperative period. The results suggest that pulmonary oxygenation is the most important determinant of mean subcutaneous oxygen tension after uncomplicated elective abdominal operations.

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.

Closure of the abdominal fascia after clean and clean-contaminated laparotomy.

This prospective, randomized study compares continuous absorbable suture (Dexon), continuous nonabsorbable suture (Surgilon) and interrupted absorbable suture (Dexon) for fascial closure of clean and clean-contaminated laparotomy wounds. Three months postoperatively, the overall frequencies were for wound dehiscence 0% (0/238), wound infection 5.5% (13/238), hernia formation 0.4% (1/238) and sinus formation 0% (0/238). After a median period of 41 months (range 14-59 months) a physical examination was performed in 93.7% (224/238) of the patients and the observed overall frequency of hernia was 3.1% (7/224). No difference was detected in incidence of wound complications when comparing the three groups. We conclude that layered closure of a laparotomy wound is safe whether using nonabsorbable or absorbable sutures and whether applying a continuous or interrupted technique in the fascial closure of clean and clean-contaminated wounds.

Intraincisional antibiotic in addition to systemic antibiotic treatment fails to reduce wound infection rates in contaminated abdominal surgery. A controlled clinical trial.

One hundred ninety patients with peritonitis at the time of abdominal surgery were allocated at random to systemic antibiotic treatment alone or systemic antibiotic treatment combined with topical application of antibiotics in the wound at the time of wound closure. The overall wound infection rate was 17 percent without significant difference between the two treatment groups (P greater than 0.80).

Clinical versus ultrasonographic evaluation of scrotal disorders.

Clinical and ultrasonographic examinations of scrotal disorders were compared in 166 patients in order to determine their ability to distinguish between those diseases requiring surgery and those requiring clinical follow-up only. Ultrasound examinations were efficient in discriminating between normal and pathological findings. Extra-testicular lesions were readily differentiated from testicular ones. Although both clinical and ultrasonographic examinations had high sensitivity (90%) in detecting testicular cancer, the number of false positive findings was smaller after ultrasound examination. This gave a predictive value of a positive test of 53% after ultrasound examination but only 33% after clinical examination. Ultrasound examination may, therefore, reduce the number of surgical explorations in the scrotum and should be performed in patients with suspected testicular pathology based on history and palpatory findings.