Comparing practice and outcome of laparoscopic liver resection between high-volume expert centres and nationwide low-to-medium volume centres.

BACKGROUND: Based on excellent outcomes from high-volume centres, laparoscopic liver resection is increasingly being adopted into nationwide practice which typically includes low-medium volume centres. It is unknown how the use and outcome of laparoscopic liver resection compare between high-volume centres and low-medium volume centres. This study aimed to compare use and outcome of laparoscopic liver resection in three leading European high-volume centres and nationwide practice in the Netherlands. METHOD: An international, retrospective multicentre cohort study including data from three European high-volume centres (Oslo, Southampton and Milan) and all 20 centres in the Netherlands performing laparoscopic liver resection (low-medium volume practice) from January 2011 to December 2016. A high-volume centre is defined as a centre performing >50 laparoscopic liver resections per year. Patients were retrospectively stratified into low, moderate- and high-risk Southampton difficulty score groups. RESULTS: A total of 2425 patients were included (1540 high-volume; 885 low-medium volume). The median annual proportion of laparoscopic liver resection was 42.9 per cent in high-volume centres and 7.2 per cent in low-medium volume centres. Patients in the high-volume centres had a lower conversion rate (7.4 versus 13.1 per cent; P < 0.001) with less intraoperative incidents (9.3 versus 14.6 per cent; P = 0.002) as compared to low-medium volume centres. Whereas postoperative morbidity and mortality rates were similar in the two groups, a lower reintervention rate (5.1 versus 7.2 per cent; P = 0.034) and a shorter postoperative hospital stay (3 versus 5 days; P < 0.001) were observed in the high-volume centres as compared to the low-medium volume centres. In each Southampton difficulty score group, the conversion rate was lower and hospital stay shorter in high-volume centres. The rate of intraoperative incidents did not differ in the low-risk group, whilst in the moderate-risk and high-risk groups this rate was lower in high-volume centres (absolute difference 6.7 and 14.2 per cent; all P < 0.004). CONCLUSION: High-volume expert centres had a sixfold higher use of laparoscopic liver resection, less conversions, and shorter hospital stay, as compared to a nationwide low-medium volume practice. Stratification into Southampton difficulty score risk groups identified some differences but largely outcomes appeared better for high-volume centres in each risk group.

Long-Term Effects of Omitting Antibiotics in Uncomplicated Acute Diverticulitis.

BACKGROUND: Traditionally uncomplicated acute diverticulitis was routinely treated with antibiotics, although evidence for this strategy was lacking. Recently, two randomized clinical trials (AVOD trial and DIABOLO trial) published short-term results of omitting antibiotics compared to routine antibiotic treatment. Both showed no significant differences regarding recovery from the initial episode, as well as rates of complicated or recurrent diverticulitis and sigmoid resection. However, both studies showed a trend of higher rates of sigmoid resection in the observational groups. Here, the long-term effects of omitting antibiotics in first episode uncomplicated acute diverticulitis were assessed. METHODS: A total of 528 patients with CT-proven, primary, left-sided, uncomplicated acute diverticulitis were randomized to either an observational or an antibiotic treatment strategy (DIABOLO trial). Outcome measures were complicated diverticulitis, recurrent diverticulitis and sigmoid resection at 24 months' follow up. Differences between the groups were explored and risk factors were identified using multivariable logistic regression. RESULTS: Complete case analyses showed no difference in rates of recurrent diverticulitis (15.4% in the observational group versus 14.9% in the antibiotic group; p = 0.885), complicated diverticulitis (4.8% versus 3.3%; p = 0.403) and sigmoid resection (9.0% versus. 5.0%; p = 0.085). Young patients (<50 years) and patients with a pain score at presentation of 8 or higher on a visual analogue pain scale were at risk for complicated or recurrent diverticulitis. In this multivariable analysis, treatment type (with or without antibiotics) was not an independent predictor for complicated or recurrent diverticulitis. CONCLUSION: Omitting antibiotics in the treatment of uncomplicated acute diverticulitis did not result in more complicated diverticulitis, recurrent diverticulitis or sigmoid resections at long-term follow up. As the DIABOLO trial was not powered for these secondary outcome measures, some uncertainty remains whether (small) non-significant differences could be true associations.

Randomized clinical trial of observational versus antibiotic treatment for a first episode of CT-proven uncomplicated acute diverticulitis.

BACKGROUND: Antibiotics are advised in most guidelines on acute diverticulitis, despite a lack of evidence to support their routine use. This trial compared the effectiveness of a strategy with or without antibiotics for a first episode of uncomplicated acute diverticulitis. METHODS: Patients with CT-proven, primary, left-sided, uncomplicated, acute diverticulitis were included at 22 clinical sites in the Netherlands, and assigned randomly to an observational or antibiotic treatment strategy. The primary endpoint was time to recovery during 6 months of follow-up. Main secondary endpoints were readmission rate, complicated, ongoing and recurrent diverticulitis, sigmoid resection and mortality. Intention-to-treat and per-protocol analyses were done. RESULTS: A total of 528 patients were included. Median time to recovery was 14 (i.q.r. 6-35) days for the observational and 12 (7-30) days for the antibiotic treatment strategy, with a hazard ratio for recovery of 0·91 (lower limit of 1-sided 95 per cent c.i. 0·78; P = 0·151). No significant differences between the observation and antibiotic treatment groups were found for secondary endpoints: complicated diverticulitis (3·8 versus 2·6 per cent respectively; P = 0·377), ongoing diverticulitis (7·3 versus 4·1 per cent; P = 0·183), recurrent diverticulitis (3·4 versus 3·0 per cent; P = 0·494), sigmoid resection (3·8 versus 2·3 per cent; P = 0·323), readmission (17·6 versus 12·0 per cent; P = 0·148), adverse events (48·5 versus 54·5 per cent; P = 0·221) and mortality (1·1 versus 0·4 per cent; P = 0·432). Hospital stay was significantly shorter in the observation group (2 versus 3 days; P = 0·006). Per-protocol analyses were concordant with the intention-to-treat analyses. CONCLUSION: Observational treatment without antibiotics did not prolong recovery and can be considered appropriate in patients with uncomplicated diverticulitis. Registration number: NCT01111253 (http://www.clinicaltrials.gov).

Comparison of extended hemicolectomy versus transverse colectomy in patients with cancer of the transverse colon.

BACKGROUND: Cancer of the transverse colon is rare and postoperative mortality tends to be high. Standard surgical treatment involves either extended hemicolectomy or transverse colectomy, depending on the location of the tumour. The aim of the present study was to compare postoperative mortality and five-year survival between these types of surgery. METHODS: For this observational study, data on patients with a tumour of the transverse colon, treated by open resection in the Dordrecht Hospital from 1989 through 2003, were derived from the database of the regional cancer registry. Information on type of resection, tumour stage, complications, postoperative mortality (30-day) and survival was abstracted from the medical files. Patients with multi-organ surgery, (sub)total colectomy or stage IV disease were excluded from the analysis, leaving a total series of 103 patients. RESULTS: Transverse colectomy comprised one third of operations, predominantly involving partial resections. Postoperative mortality was 6% (2/34) after transverse colectomy and 7% (5/69) after extended hemicolectomy. Five-year survival was slightly higher for the hemicolectomy group (61% versus 50%), but this difference did not reach statistical significance (p = 0.34). CONCLUSION: Our results confirm the high postoperative risk after surgery for cancer of the transverse colon and show that this risk does not depend on the type of surgery. Considering the satisfactory results after partial transverse colectomy, segmental resections may be considered as an option for the treatment of localised tumours of the transverse colon.

Outcome of surgery for colovesical and colovaginal fistulas of diverticular origin in 40 patients.

INTRODUCTION: According to literature, colonic resection with a primary anastomosis and no defunctioning ileostomy is a safe treatment for colovesical or colovaginal fistula of diverticular origin. This study investigates the outcome of surgery for this patient group in a regional hospital. METHODS: Patients were obtained from a prospective database in the period 2004-2011. Several variables were investigated for their relation with surgical outcome. RESULTS: A colovesical (n = 35) or colovaginal (n = 5) fistula was diagnosed in 18 men and 22 women. The mean age was 69 years (range, 45-90). A rectosigmoid resection with primary anastomosis was performed in 32 patients. Fourteen patients received a defunctioning ileostomy. Eight patients were treated with a Hartmann procedure. Overall 30-day treatment-related morbidity and mortality was 48 and 8 %, respectively. Major morbidity, because of anastomotic leakage, was mainly observed in the primary anastomosis group without a defunctioning ileostomy. Morbidity and mortality were associated with high body mass index, diabetes, use of corticosteroids, and American Society of Anesthesiologists classification, though not significantly. CONCLUSIONS: One should be liberal in the use of a defunctioning ileostomy in case of a primary anastomosis after colonic resection for a diverticular fistula, in order to prevent high morbidity rates due to anastomotic leakage.

Treatment of grade 2 and 3 hemorrhoids with Doppler-guided hemorrhoidal artery ligation.

AIM: We evaluated the results of the Doppler-guided hemorrhoidal arterial ligation (DG-HAL) method in the management of symptomatic grade 2 and 3 hemorrhoids. PATIENTS AND METHODS: Between June 2005 and March 2006, 110 consecutive patients with symptomatic grade 2 and 3 hemorrhoids according to the DG-HAL method were treated. All procedures were performed in daycare under spinal anesthesia. The primary objective was the reduction in hemorrhoidal gradation as determined by proctoscopy; the secondary was patient satisfaction. This was measured by interviewing patients over the telephone. RESULTS: The average age was 47.6 years. 42 patients had grade 2 hemorrhoids, 68 grade 3. An average of 7.3 ligations were placed. Proctoscopy showed that, after 6 weeks, 97 (88%) patients had a significant improvement in their hemorrhoidal gradation. After an average follow-up of 37 weeks, 93 of the 110 (84.5%) patients were satisfied with the postoperative result. Mortality was 0% and morbidity 3%. CONCLUSION: DG-HAL is a safe and effective treatment in the management of symptomatic grade 2 and 3 hemorrhoids.

Effects of brain death on stress and inflammatory response in the human donor kidney.

BACKGROUND: After kidney transplantation, a decreased graft survival is seen in grafts from brain dead donors compared to living donors, possibly related to a progressive inflammatory reaction in the graft. In this study, we focused on the effects of brain death on the inflammatory response (adhesion molecules, leukocyte infiltration, and gene expression) and stress-related heat shock proteins in the human kidney. Research outcomes and clinical donor parameters were linked to outcome data after transplantation. METHODS: Human kidney biopsy specimens were obtained during organ retrieval from brain dead and living organ donor controls. On these specimens, immunohistochemistry and semiquantitative RT-PCR were performed. Regression analyses were performed connecting results to outcome data of kidney recipients. RESULTS: In brain death, immunohistochemistry showed an increase of E-selectin and interstitial leukocyte invasion versus controls; RT-PCR showed an increase of gene expression of HO-1 and Hsp70. One and 3 years after transplantation, high ICAM and VCAM expression proved to have a negative effect on kidney function in brain dead and living kidneys, while HO-1 proved to have a strongly positive effect, but only in kidneys from living donors. CONCLUSIONS: E-selectin expression and interstitial leukocyte accumulation in brain dead donor kidneys indicate an early phase inflammatory state prior to organ retrieval. Also, brain death causes a stress-related response resulting in upregulation of potentially protective heat shock proteins. The upregulation of HO-1 is beneficial in living donor kidneys, but might be inadequate in brain death.

Donor brain death reduces survival after transplantation in rat livers preserved for 20 hr.

BACKGROUND: Eighty percent of donor organs come from donors who have suffered brain trauma (brain-dead donors). This unphysiological state alters the hemodynamic and hormonal status of the organ donor. This can cause organ injury, which has been suggested to alter the immunological or inflammatory status of the organ after transplantation, and may lead to increased sensitivity of the organ to preservation/transplantation injury. In this study we asked the question: does brain death cause injury to the liver that decreases successful liver preservation? METHODS: The rat liver transplant model was used to compare survival in rats receiving a liver from a brain-dead donor versus a non-brain-dead donor. Brain death was induced by inflation of a cranially placed balloon catheter. The rats were maintained normotensive with fluid infusion for 6 hr. The livers were flushed with University of Wisconsin (UW) solution and immediately transplanted or cold stored for 20 hr before transplantation. RESULTS: Recipient survival with immediately transplanted livers or those stored for 20 hr was 100% with livers from non-brain-dead donors. However, survival decreased when livers were procured from brain-dead donors. Survival was 75% (6/8) when storage time was 0 hr and 20% (2/10) when the liver was cold stored for 20 hr before transplantation. CONCLUSION: This study shows that brain death induces alterations in the donor liver that make it more sensitive to preservation/reperfusion injury than livers from donors without brain death. The mechanism of injury to the liver caused by brain death is not known. Because most livers used clinically for transplantation come from brain-dead donors, it is possible that poor function of these livers is due to the intrinsic condition of the donor organ, more than the quality of the preservation. Methods to treat the brain-dead donor to improve the quality of the liver may be needed to allow better preservation of the organ and to give better outcome after liver transplantation.

Effects of brain death and hemodynamic status on function and immunologic activation of the potential donor liver in the rat.

OBJECTIVE: To assess the effect on the function and immunologic status of potential donor livers of the duration of brain death combined with the presence and absence of hemodynamic instability in the donor. SUMMARY BACKGROUND DATA: Brain death, regarded as a given condition in organ transplantation, could have significant effects on the donor organ quality. METHODS: Brain death was induced in Wistar rats. Short or long periods of brain death in the presence or absence of hemodynamic instability were applied. Sham-operated rats served as controls. Organ function was studied by monitoring standard serum parameters. The inflammatory status of the liver was assessed by determining the immediate early gene products, the expression of cell adhesion molecules, and the influx of leukocytes in the liver. RESULTS: Progressive organ dysfunction was most pronounced in hemodynamically unstable brain-dead donors. Irrespective of hemodynamic status, a progressive inflammatory activation could be observed in brain-dead rats compared with controls. CONCLUSIONS: Brain death causes progressive liver dysfunction, which is made worse by the coexistence of hemodynamic instability. Further, brain death activates the inflammatory status of the potential donor liver, irrespective of the presence of hypotension. The changes observed may predispose the graft to additional damage from ischemia and reperfusion in the transplant procedure.

Induction of organ dysfunction and up-regulation of inflammatory markers in the liver and kidneys of hypotensive brain dead rats: a model to study marginal organ donors.

BACKGROUND: Marginal donors exposed to the full array of effects induced by brain death are characterized by low success rates after transplantation. This study examined whether organs from marginal brain dead animals show any change in organ function or tissue activation making them eventually more susceptible for additional damage during preservation and transplantation. METHODS: To study this hypothesis we first focused on effects of brain death on donor organ quality by using a brain death model in the rat. After induction of brain death, Wistar rats were ventilated for 1 and 6 hr and then killed. Sham-operated rats served as controls. Organ function was studied using standard serum parameters. Tissue activation of liver and kidney was assessed by staining of immediate early gene products (IEG: FOS, JUN), and inflammatory markers; cell adhesion molecules (Intercellular adhesion molecule-1, vascular cell adhesion molecule-1), leukocyte infiltrates (CD45, T cell receptor, CD8, CD4), and MHC class II. RESULTS: During brain death progressive organ dysfunction was observed that coincided with a significant increase in activation of immediate early genes, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, CD45, and MHC class II versus nonbrain dead controls. In liver tissue also the markers for T cell receptor and CD8 significantly increased. CONCLUSIONS: These findings suggest that an immune activation with increased endothelial cell activation and immediate early gene expression occurs in marginal donors after brain death induction. We suggest that brain death should not longer be regarded as a given nondeleterious condition but as a dynamic process with potential detrimental effects on donor organs that could predispose grafts for increased alloreactivity after transplantation.

Extended preservation and effect of nitric oxide production in liver transplantation.

Liver transplantation (Ltx) has become a routine procedure for patients with end-stage liver disease. Despite ongoing progress on short- and long-term graft survival, primary dysfunction (PDF) remains a major problem. PDF is significantly associated with the duration of cold ischemia- and, possibly, with reperfusion-related injury. Nitric oxide (NO) has many physiological functions and plays an important role in modulating tissue injury. However, the mechanism of NO action in ischemia/reperfusion injury after Ltx is thus far unknown. In this study we investigated the role of inducable NO synthase (iNOS) in the liver after preservation with UW solution using the orthotopic Ltx model in the rat. Male Brown Norway rats were used for the Ltx procedure. After donor hepatectomy, livers were stored on ice-cold UW solution for 24 or 40 h and subsequently transplanted. A control group consisted of rats with Ltx after less than 1 h storage. Post-transplant blood samples were taken at 48 h to determine standard parameters for liver injury (aspartate transaminase, lactate dehydrogenase). Liver biopsies were obtained for detection of expression of iNOS (western blot) 24 and 48 h post-transplant. We observed that a preservation time of 24 h in UW solution presents no problem for graft survival after Ltx in rats with some brain function and in healthy animals. After 40 h preservation, liver damage is obvious and graft survival reduced, indicating the limits of cold storage may be within reach. With longer preservation times, more NOs was detected in liver tissue. This finding suggests that NO has a role in ischemia/reperfusion-related injury. Current intervention with NOS inhibitors will reveal whether NO has a negative or a positive effect on graft survival after Ltx.

Tissue pH in cold-stored human donor livers preserved in University of Wisconsin solution. A noninavasive clinical study with 31P-magnetic resonance spectroscopy.

It is not known whether the tissue acidosis that accompanies cold storage is the beginning of irreversible cell injury, ultimately leading to cell death, or whether it is a natural "protective" mechanism for cells to survive hypoxic periods. To answer this question, the tissue pH of 45 cold-stored human donor livers preserved in University of Wisconsin solution (UW) was assessed shortly before implantation using noninvasive 31P magnetic resonance spectroscopy. We conclude that tissue pH during cold storage may be partly dependent upon hepatic glycogen stores and donor age. The wide range of tissue pH values that was observed at the time of implantation does not result in significant effects on cellular damage after transplantation. This indicates that tissue pH is not a major determinant for the viability of UW solution-preserved human donor livers, as indicated by postoperative hepatocellular damage and liver synthesis function. The membrane stabilizing and buffering capacity of UW solution appears to protect liver viability against tissue acidosis. Our results also indicate that liver tissue pH can be lower than has been previously assumed in the literature without significant adverse effects on liver viability.

Tissue hydration in kidneys during preservation: a relaxometric analysis of time-dependent differences between cortex and medulla.

Cold preservation of donor organs induces hypothermia-related tissue edema as a result of a reduced activity of the ATP-dependent sodium pump at low temperatures. Hypothermia-induced tissue edema occurs in kidney preservation and is a significant risk factor for delayed graft function (DGF) after transplantation. DGF remains a major problem in kidney transplantation and is significantly associated with preservation injury. The state of hydration of cold-stored organs can be assessed from a biopsy for determination of the wet/dry weight ratio. As a non-invasive method to determine tissue hydration MRI T1 and T2 relaxometry can be used. In this study we have compared changes in tissue hydration in UW-preserved porcine kidneys with increasing cold ischemia times (CIT) using wet/dry weight ratio and MR ralaxometry. The results of the two techniques were correlated to evaluate the use of MR relaxometry. Wet/dry weight ratios of the renal cortex decreased with prolonged CIT (P < 0.01) whereas those of the medulla did not change significantly. T1 values of the cortex decreased with prolonged CIT (P < 0.01). T2 values of the cortex showed a non-significant decline with increased CIT. No significant changes in T1 and T2 were found in the medulla. The correlation between T1 and the wet/dry weight ratio of the cortex was significant (P = 0.05, linear correlation coefficient 0.8698). We conclude that MR relaxometry can be a valuable noninvasive technique to assess tissue hydration in cadaveric donor kidneys before transplantation.