Characteristics of de novo cancer in liver transplant recipients.

Liver transplant recipients receive immunosuppressive treatment to avoid organ rejection, increasing the risk of developing de novo cancer after transplantation. We investigated the cumulative incidence of de novo cancer in a cohort of Danish liver transplant recipients. The study was a retrospective cohort study of adult liver transplant recipients transplanted at Rigshospitalet, Copenhagen, Denmark, between January 1, 2010, and December 31, 2019. De novo cancer was defined as cancer arising at least 30 days after liver transplantation, excluding relapses from prior cancers and donor-derived cancers. We determined the incidence of de novo cancer in the cohort using the Aalen-Johansen estimator, with death and retransplantation as competing risks. We included 389 liver transplant recipients and identified 47 recipients (12%) with de novo cancer after liver transplantation, including 25 recipients with non-melanoma skin cancers. The cumulative incidences at 5 years after liver transplantation for all cancers and non-skin cancers were 10.7% and 4.9%, respectively. De novo cancer after liver transplantation is relatively common, with the majority being non-melanoma skin cancer. Future studies of sufficient size are needed to identify risk factors for de novo cancer after liver transplantation.

Enhanced recovery after surgery is feasible and safe in liver transplantation: a cohort study.

BACKGROUND: The principles of enhanced recovery after surgery (ERAS) are being applied to still more advanced procedures. Liver transplantation offers a unique opportunity for a multimodal approach including donor care as well. Our objective was to determine if ERAS was applicable and safe in orthotopic liver transplantation (OLT). METHODS: A national single centre retrospective study showing the implementation of ERAS from 2013 to 2019 with the proceeding 2 years serving as baseline. The primary endpoints were mortality, length of stay (LOS) in the ward and intensive care unit stay. Secondary endpoints were complications estimated by Dindo-Clavien classification, comprehensive complication index (CCI®) and re-admissions. RESULTS: A total of 334 patients were included. LOS was significantly reduced from a median of 22.5 days at introduction to 14 days at 2019. Cold ischaemia time was reduced from a mean of 10.7 to 6.0 h and the use of blood products (erythrocytes, plasma and thrombocytes) from a median of 28 to 6 units. Complications were reduced in severity. Mortality and readmission rates were not affected. CONCLUSION: ERAS principles are safe and recommended in patients undergoing OLT resulting in reduced severity of complications and LOS without affecting re-admissions or mortality.

High-dose preoperative glucocorticoid for prevention of emergence and postoperative delirium in liver resection: A double-blinded randomized clinical trial substudy.

BACKGROUND: Emergence delirium (ED) and postoperative delirium (POD) are associated with increased morbidity and mortality and occur in up to one-third of patients undergoing major non-cardiac surgery, where the underlying pathogenesis is multifactorial, including increased inflammation. We aimed to assess the effect of pre-operative high- versus low-dose glucocorticoid on the occurrence of ED and POD. METHODS: This was a substudy from a randomized, double-blinded clinical trial. Patients ≥18 years, undergoing open liver resection were randomized 1:1 to high-dose (HD, 10 mg/kg methylprednisolone) or low-dose (LD, 8 mg dexamethasone) glucocorticoid and assessed for ED and POD for a maximum of 4 days during hospitalization. The 3-min Diagnostic Interview for CAM-defined delirium (3D-CAM) was used for assessment, 15 and 90 min after arrival in the post-anesthesia care unit (PACU), and subsequently once daily in the ward. RESULTS: Fifty-three patients were included in this secondary substudy (26 HD-group and 27 LD-group). ED occurred in n = 5 HD versus n = 6 LD patients 15 min after PACU arrival. At 90 min after PACU arrival, 4 patients had ED, all from LD-group, and resulted in significantly longer PACU admission, 273 versus 178 min in ED versus Non-ED patients. During the first 4 days in the ward, n = 5 patients had at least one occurrence of POD, all from LD-group. CONCLUSIONS: The primary finding of the current substudy was a lower occurrence of ED/POD in the PACU 90 min after arrival and during the first four postoperative days in patients receiving high-dose glucocorticoid compared with patients receiving low-dose glucocorticoid. The two study groups were not evenly balanced concerning known explanatory factors, i.e., age and size of surgery, which calls for larger studies to elucidate the matter.

Does multimodal perioperative pain management enhance immediate and short-term outcomes after living donor partial hepatectomy? A systematic review of the literature and expert panel recommendations.

BACKGROUND: The optimal analgesic strategy for patients undergoing donor hepatectomy is not known and the potential short- and long-term physical and psychological consequences of complications are significant. OBJECTIVES: To identify whether a multimodal approach to pain of the donor intraoperatively enhances immediate and short-term outcomes after living liver donation, and to provide international expert panel recommendations. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. PROSPERO 2021 CRD42021260699. RESULTS: Nine studies assessing multi-modal analgesia strategies were included in a qualitative assessment. Interventions included local, regional, and neuro-axial anesthetic techniques, pharmacological intervention (NSAIDs, COX-2 inhibitors, ketamine, dexmedetomidine, and lidocaine), and acupuncture. Overall, there was a significant (40%) reduction in opioid requirement on day 1 and a significant reduction in pain scores in the intervention vs control groups. Significant reductions in either length of stay or post-operative complications were demonstrated in four of nine studies. CONCLUSIONS: Opioid use for patients undergoing donor hepatectomy is likely to impact both their short- and long-term outcomes. To reduce post-operative pain scores, shorten length of hospital stay, and promote earlier post-operative return of bowel function, we recommend that multi-modal analgesia be offered to patients undergoing living donor hepatectomy. Further research is required to confirm which multi-modal techniques are most associated with enhanced recovery in living liver donors.

Morbidity and mortality after liver surgery for colorectal liver metastases: a cohort study in a high-volume fast-track programme.

BACKGROUND: For colorectal liver metastases, surgery is a high-risk procedure due to perioperative morbidity. The objective was to assess severity of complications after fast-track liver surgery for colorectal liver metastases and their impact on morbidity and mortality. METHODS: All patients were treated according to the same fast-track programme. Complications were graded according to the Clavien-Dindo classification for patients undergoing surgery from 2013 to 2015. Correlation between complications and length of stay was analysed by multivariate linear regression. RESULTS: 564 patient cases were included of which three patients died within 3 months (0.53%, 95% CI: 0.17-1.64%). Complications were common with Grade ≤ 2 in 167 patients (30%) and ≥ Grade 3a in 93 (16%). Patients without complications had a mean length of stay of 4.1 days, which increased with complications: 1.4 days (95% CI: 1.3-1.5) for Grade 2, 1.7 days (1.5-2.0) for Grade 3a, 2.3 days (1.7-3.0) for Grade 3b, 2.6 days (1.6-4.2) for Grade 4a, and 2.9 days (2.8-3.1) for Grade 4b. Following were associated with increased length of stay: complication severity grade, liver insufficiency, ascites, biliary, cardiopulmonary, and infectious complications. CONCLUSIONS: Complications after liver surgery for colorectal liver metastases, in a fast track setting, were associated with low mortality, and even severe complications only prolonged length of stay to a minor degree.

Rapid decline in 51Cr-ethylenediaminetetraacetic acid-measured renal function during the first weeks following liver transplantation.

BACKGROUND: Renal dysfunction is a serious late complication after liver transplantation (LTX), but there are no studies addressing the early changes associated with this complication. METHODS: We prospectively studied glomerular filtration rate (GFR) before and at 1, 3 and 12 weeks after LTX using 51Cr-labelled ethylenediaminetetraacetic acid clearance in 37 adult consecutive patients who underwent non-acute first LTX. RESULTS: The mean (±SD) age was 49.5 ± 9.5 years, and the male:female sex ratio was 21:16. Diagnoses were autoimmune liver diseases (17), alcoholic cirrhosis (10) and other diseases (10). Immunosuppressive treatment consisted predominantly of triple-drug therapy. A total of 27 of the 37 patients were eligible for GFR analysis at all times. The mean (±SD) GFR was 86 ± 26 mL/min/1.73 m2 before LTX, and 77 ± 30 mL/min/1.73 m2 at 1 week, 64 ± 27 mL/min/1.73 m2 at 3 weeks and 64 ± 23 mL/min/1.73 m2 at 12 weeks after LTX, comparable to a reduction in mean GFR compared with baseline values of 10% (P = 0.1907), 25% (P = 0.0010) and 26% (P = 0.0007). Age and number of blood transfusions during surgery were identified as risk factors for this decline as well as gender, but not pre-transplant diagnosis, model of end-stage liver disease score, cold ischaemia time or post-transplant area under the curve tacrolimus during Days 0-14. CONCLUSIONS: Using measured rather than estimated GFR, our results show that severe renal impairment occurs during the first week after LTX. These results emphasize the need for more studies addressing renoprotective treatment strategies.

Increasing Incidence of Pelvic Sepsis Following Ileal Pouch-Anal Anastomosis for Ulcerative Colitis in Denmark: A Nationwide Cohort Study.

BACKGROUND: The risk of pelvic sepsis following IPAA for ulcerative colitis may have changed with changes in medical and surgical treatment, but data are scarce. OBJECTIVES: This study aims to examine temporal changes in the risk of pelvic sepsis following IPAA for ulcerative colitis and to ascertain risk factors associated with pelvic sepsis. DESIGN: This is a nationwide cohort study. SETTING: This study was conducted in Denmark from 1996 to 2013. PATIENTS: Patients were operated on with an IPAA for ulcerative colitis. MAIN OUTCOME MEASURES: Pelvic sepsis was defined and validated as the occurrence of anastomotic leakage, pelvic abscesses or fistulas, or an operation for these conditions, recorded in a nationwide registry. Cumulative risks were calculated by using death as a competing risk. Multivariate Cox regression was used to examine the effects of calendar periods (1996-1999, 2000-2004, 2005-2009, and 2010-2013) on hazards ratios for pelvic sepsis, adjusting for age, sex, comorbidity, annual hospital volume, pelvic sepsis in the 12 months preceding surgery, operative stage (1-, 2-, modified 2-, or 3-stage), laparoscopy, and preoperative treatment with biological medicine within 12 weeks before surgery. RESULTS: Of 1456 patients, 244 (16.8%) experienced pelvic sepsis. The 1-year risk increased by calendar period (1996-1999: 2.5%, 2000-2004: 4.5%, 2005-2009: 7.4%, and 2010-2013: 9.6%). The adjusted hazard ratio for pelvic sepsis increased by an average 4.4% (95% CI, 1.3-7.6) per year in the study period. In general, patients were older and had more comorbidities at IPAA in recent years than in earlier years, and more had experienced pelvic sepsis in the 12 months preceding the operation. LIMITATIONS: This study was register based. There were no data on important clinical variables to determine the causes of an increased risk over calendar periods. CONCLUSION: In this nationwide cohort study, the 1-year risk of pelvic sepsis following primary IPAA for ulcerative colitis increased 4-fold from 1996 to 2013. See Video Abstract at http://links.lww.com/DCR/A956.

Second Generation of a Fast-track Liver Resection Programme.

BACKGROUND: Recent developments in perioperative pathophysiology and care have documented evidence-based, multimodal rehabilitation (fast-track) to hasten recovery and decrease morbidity and hospital stay in several major surgical procedures. The aim of this study was to investigate the effect over time of a modified previously published fast-track programme in unselected patients undergoing open or laparoscopic liver resection. METHODS: A prospective study includes the first 121 consecutive patients following an updated fast-track programme for liver resection. High-dose methylprednisolone was given to all patients before surgery, 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. The discharge criteria were (1) pain sufficiently controlled by oral analgesics only; (2) patient comfortable with discharge; (3) no untreated complications. RESULTS: The median length of stay (LOS) for all patients was 4 days, with 2 days after laparoscopic vs. 4 days for open resections. The median LOS after major hepatectomies (≥3 segments) was 5 days. The readmission rate was 6% and the 30-day mortality zero. The LOS decreased compared to our first-generation fast-track programme with LOS 5 days. CONCLUSIONS: Fast-track principles for perioperative care and early discharge are safe even after major liver resection. The introduction of high-dose steroids preoperatively might have facilitated a shorter LOS. Routine discharge on POD 1 or 2 after laparoscopic resection and on POD 4 after open liver resection has proven to be feasible.

Outcome in patients treated with isolated liver transplantation for familial transthyretin amyloidosis to prevent cardiomyopathy.

BACKGROUND: Familial transthyretin (TTR) amyloidosis is caused by different TTR mutations resulting in different clinical phenotypes of the disease. The Leu111Met mutation causes severe restrictive cardiomyopathy. Liver transplantation (LTx) is an established treatment option for patients with TTR amyloidosis; however, information on outcome after isolated LTx in patients with Leu111Met mutation amyloidosis is limited. METHODS: Between 2005 and 2012, six patients with TTR Leu111Met amyloidosis underwent isolated orthotopic LTx. None suffered from neuropathy. Prior to LTx, patients presented with echocardiographic manifestations of early cardiac amyloid involvement and in five endomyocardial biopsy was positive for TTR amyloid. RESULTS: Median age at LTx was 45.5 yr (range 39-54), and four were male (67%). All patients were alive at a median follow-up of 56.6 months (range 18-104). No surgical complications occurred. Two patients (33%) underwent cardiac transplantation during follow-up due to progressive cardiomyopathy. The remaining four patients experienced no echocardiographic or clinical deterioration of cardiac function following LTx. CONCLUSION: Isolated LTx appears to be a valuable treatment option for patients with familial TTR amyloidosis due to Leu111Met mutation. Appropriate timing of LTx is of utmost importance to avoid development of severe amyloid cardiomyopathy and the need for combined heart and liver transplantation.

Ventilatory strategy during liver transplantation: implications for near-infrared spectroscopy-determined frontal lobe oxygenation.

BACKGROUND: As measured by near infrared spectroscopy (NIRS), cerebral oxygenation (ScO2) may be reduced by hyperventilation in the anhepatic phase of liver transplantation surgery (LTx). Conversely, the brain may be subjected to hyperperfusion during reperfusion of the grafted liver. We investigated the relationship between ScO2 and end-tidal CO2 tension (EtCO2) during the various phases of LTx. METHODS: In this retrospective study, 49 patients undergoing LTx were studied. Forehead ScO2, EtCO2, minute ventilation (VE), and hemodynamic variables were recorded from the beginning of surgery through to the anhepatic and reperfusion phases during LTx. RESULTS: In the anhepatic phase, ScO2 was reduced by 4.3% (95% confidence interval: 2.5-6.0%; P < 0.0001), EtCO2 by 0.3 kPa (0.2-0.4 kPa; P < 0.0001), and VE by 0.4 L/min (0.1-0.7 L/min; P = 0.0018). Conversely, during reperfusion of the donated liver, ScO2 increased by 5.5% (3.8-7.3%), EtCO2 by 0.7 kPa (0.5-0.8 kPa), and VE by 0.6 L/min (0.3-0.9 L/min; all P < 0.0001). Changes in ScO2 were correlated to those in EtCO2 (Pearson r = 0.74; P < 0.0001). CONCLUSION: During LTx, changes in ScO2 are closely correlated to those of EtCO2. Thus, this retrospective analysis suggests that attention to maintain a targeted EtCO2 would result in a more stable ScO2 during the operation.

[The quality of the survey-questionnaire Danish National Survey of Patient Experiences is questionable]. / Den Landsdækkende Undersøgelse af Patientoplevelser har tvivlsom kvalitet.

We question the social science methodology in survey-questionnaire Danish National Survey of Patient Experiences (LUP). The results from the survey are part of the accreditation system in The Danish Health-care Quality Programme (DDKM). The methodological validity is researched through LUP-publications. We find that LUP has doubtful scientific quality which means that the validity of the survey results as such is questionable. Since this has consequences for the practical, economic, political and health-care decisions, we recommend that the total accreditation programme should be reconsidered.

[Improved questionnaire concerning the Danish National Survey of Patient Experiences]. / Forbedring af spørgeskema vedrørende Den Landsdækkende Undersøgelse af Patientoplevelser.

We question the evaluation-design of the Danish National Survey of Patient Experiences (LUP). The results from the survey are part of the accreditation system in The Danish Health-care Quality Programme. How the evaluation-design may be improved is researched through a revised questionnaire tested during a three-month period. We find that the existing evaluation-model must be replaced by a developmental evaluation-approach/model which includes valid measures of patient-satisfaction, other target-groups, and allows for the context of the specific health-care sector.

Construct validity of the reporter-interpreter-manager-educator structure for assessing students' patient encounter skills.

PURPOSE: The aim of this study, done in Denmark, was to explore the construct validity of a Reporter-Interpreter-Manager-Educator (RIME)-structured scoring format for assessing patient encounter skills. METHOD: The authors developed a RIME-structured scoring form and explored its construct validity in a two-step procedure. The first step (implemented in 2009) was a randomized, controlled, experimental study in which the performance of three groups (16 fourth-year medical students, 16 sixth-year medical students, and 16 interns) was assessed in two simulated patient encounters. The second step (carried out during 2009-2010) was an observational study of patient encounter skills where clinician examiners used the scoring form in end-of-clerkship oral examinations of three consecutive cohorts of a total of 547 fourth-year medical students. RESULTS: In the experimental study, RIME scores showed significant difference between the three groups-fourth-year students, mean 41.7 (standard deviation [SD] 11.0); sixth-year students, mean 48.2 (SD 10.9); and interns, mean 61.9 (SD 8.5), one-way ANOVA, P < .0001-and showed a progression over the four RIME elements with participants' increasing competence.In the observational study, the mean RIME score was higher (83.8 [SD 15.5]), and advanced RIME levels were frequently missing or scored "not relevant" by the clinician examiners. CONCLUSION: In an experimental setup, the RIME structure demonstrated construct validity in terms of reflecting progress in competence in managing patient encounters when assessed according to an advanced criterion. However, clinician examiners may tacitly score the elements according to what can be expected at a certain level of student experience.

[Resuscitation and abdominal surgical aspects of damage control surgery]. / Resuscitation og abdominalkirurgiske aspekter ved damage control-kirurgi.

In multitrauma patients continuous bleeding is one of the major killers. Coagulation defects have been shown to be a primary event and to occur very early in multitrauma patients (acute traumatic coagulopathy). It is enhanced by acidosis, hypothermia and further coagulation disorders in the "bloody vicious cycle". Due to this a new resuscitation practice has been defined; damage control resuscitation, consisting of hypotensive resuscitation (restricted use of crystalloids), haemostatic resuscitation (balanced use of blood components) in combination with surgical haemostatic procedures (damage control surgery).

[Damage control surgery--a survey of a Cochrane review]. / Damage control kirurgi--en gennemgang af et Cochranereview.

Damage Control Surgery (DCS) has been the approach in dealing with multi-trauma patients for the last 15 years. In this Cochrane-review the authors seek to compare the outcome of DCS with the outcome after the conventional strategy which is often a time-consuming operation with definitive repair. However, no randomised controlled trials are found, and thus it is not possible to say whether DCS is superior to the conventional approach or not. It is not possible to perform any RCT with these patients. According to literature in general on this subject we believe, nevertheless, that the principles in DCS should be followed.

Factors associated with the development of cytomegalovirus infection following solid organ transplantation.

BACKGROUND: Infection with cytomegalovirus (CMV) remains a potentially serious complication in transplant patients. In this study we explored the risk factors for CMV infection in the 12 months following a solid organ transplantation (n = 242) in patients monitored for CMV infection from 2004 to 2007. METHODS: CMV infection was defined as 2 consecutive quantifiable CMV-polymerase chain reaction (PCR) values or 1 measurement of >3000 copies/ml. Data describing pre- and post-transplantation variables were extracted from electronic health records. Time to CMV infection was investigated using Cox proportional hazards analysis. RESULTS: Overall, 31% (75/242) of solid organ transplant patients developed CMV infection: 4/8 (50.0%) heart, 15/43 (34.9%) liver, 30/89 (33.7%) lung and 26/102 (25.5%) kidney transplant patients. The risk of CMV infection according to donor (D)/recipient (R) CMV serostatus (positive + or negative-) was highest for D+/R-(adjusted hazard ratio 2.6, 95% confidence interval 1.6-4.2) vs D+/R+, and was reduced for D-/R+(adjusted hazard ratio 0.2, 95% confidence interval 0.2-0.8) vs D+/R+. CONCLUSION: Positive donor CMV-serostatus is a major risk factor for CMV-infection in CMV-na ve recipients, but also in recipients with positive CMV-serostatus. Conversely, if donor is CMV serostatus is negative, the risk of CMV infection is low, irrespective of recipients CMV-serostatus. These findings suggest poorer immune function towards donor-induced strains of CMV versus recipient own latent strains.