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Background and objective: Acute mesenteric ischemia (AMI) has a high mortality rate due to the development of bowel necrosis. Patients are often ruled outside active care if a large proportion of small bowel is necrotic. With the development of treatment for short bowel syndrome (SBS) and intestinal transplantation methods, long-term survival is possible even after extensive small bowel resections. This study aims to assess the incidence of SBS and potentially suitable candidates for intestinal transplantation among patients treated for AMI.Methods: This population-based retrospective study comprised patients aged less than 70 years and diagnosed with AMI between January 2006 and October 2020 in Helsinki and Uusimaa health care district, Finland.Results: Altogether, AMI was diagnosed in 711 patients, of whom 133 (19%) were aged below 70. An intervention was performed in 110 (83%) patients. Of these 133 patients, 16 (12%) were ruled outside active treatment due to extensive small bowel necrosis at exploratory laparotomy, of whom 6 (5%) were potentially suitable for intestinal transplantation. Two patients were considered as potential candidates for intestinal transplantation at bowel resection but died of AMI. Nine (7%) patients needed parenteral nutrition after resection, and two of them (2%) developed SBS. Only one patient needed long-term parenteral nutrition after hospital discharge. This patient remained dependent on parenteral nutrition but died before evaluation of intestinal transplantation could be carried out while the other patient was able to return to enteral nutrition.Conclusions: A small number of patients with AMI below 70 years of age are potentially eligible for intestinal transplantation.

The aim of the study was to assess long-term morbidity in children operated for choledochal malformation (CM) by relating clinical complications to liver histopathology, follow-up imaging, liver stiffness, and biochemistry. A single-center retrospective follow-up study including all CM patients (n = 55, 71% girls) treated during 1976 to 2018 was performed. Mann-Whitney Utest and Spearman rank correlation were used for statistical analyses. During median follow-up of 5.8 (interquartile range, 2.5–12) years, 1 patient was lost to follow-up whereas all survived. Intraoperative liver biopsies showed fibrosis in 32%, and patients with Metavir stage =2 were younger at surgery (0.36 [0.11–1.9] vs 3.8 [0.72–10.5] years, P= 0.024) than those without fibrosis. Overall, 21% had long-term complications including cholangitis in 9 (>2 episodes in 5) patients, anastomotic stricture in 2 referred patients and adhesive volvulus or hepatocellular carcinoma in 1 each. Anastomotic strictures were successfully managed nonoperatively and hepatocellular carcinoma with thermoablation. In postoperative magnetic resonance cholangiography (MRCP) performed 6.4 (3.6–16) years after hepaticojejunostomy, diameters of both main intrahepatic ducts had decreased significantly to 3.0 (2.5–3.5) mm (P= 0.0001) but a distal cyst stump was remaining in 30% with a length of 6.0 (4.0–20) mm that associated with operation age (r= 0.71, P= 0.015) and fusiform CM type. Follow-up ultrasound revealed mild dilation of intrahepatic bile ducts in 6.3% and mildly to moderately elevated liver biochemistry in 23%, and liver stiffness (>7 kPa) in 22%. Whilst cholangitis was the most common postoperative problem, individual patients experienced other more significant complications and one quarter of patients showed evidence of underlying liver dysfunction.

Supplemental Digital Content is available in the text

Introduction: Recently new standards for reporting outcomes of bile duct injury (BDI) have been proposed. It is unclear how these treatment outcomes are reflected in quality of life (QOL). The aim of this study was to report outcomes and QOL after repair of major BDI and compare repairs by hepatobiliary surgeon to repairs by non-hepatobiliary surgeons. Methods: This was a retrospective study of patients treated for major (Strasberg E-type) BDI after cholecystectomy at a tertiary hepatobiliary center. Outcomes were assessed using Cho-Strasberg proposed standards. QOL was assessed using Short Form Health Survey (SF-36) and the gastrointestinal QOL-index (GIQLI). Patients undergoing uneventful cholecystectomy matched by age, urgency, and duration of follow-up were used as controls. Results: Fifty-two patients with major BDI treated between 2000 and 2016 were included (42% male, median age 53 years). Thirty-seven (71%) patients attained primary patency (29 (83%) if primarily operated by a hepatobiliary surgeon). Actuarial primary patency rate (grade A result) at 1, 3, and 5 years was 58%, 56%, and 53% in the whole cohort, and 83%, 80%, and 80% in patients primary treated by a hepatobiliary surgeon, respectively. At 3-year follow-up 6 (11.5%) patients obtained grade B, 10 (19.2%) grade C, and 7 (13.5%) grade D result. QOL was similar in patients with BDI and controls (median SF-36 physical component 51.7 and 53.6, p= 1.0, mental component 53.3 and 53.4, p= 1.0, GIQLI 109.0 and 123.0, p= 0.174, respectively) at median 90 (IQR 70–116) months from cholecystectomy. QOL was similar regardless of outcome grade. Conclusion: First attempt to repair a severe BDI should be undertaken by a hepatobiliary surgeon. However, long-term QOL is not affected even by severe BDI, and QOL is not associated with the grade of the outcome.

In a large prospective randomized open-label international trial, liver transplant recipients for HCC were randomized to receive non-mTOR-inhibitor-based-treatment or mTOR-inhibitor-based-treatment. Results indicate overall sirolimus does not improve long-term recurrence-free survival beyond 5 years while a benefit was seen in low-risk patients. Supplemental digital content is available in the text.

The prevalence of alcohol use among Finnish liver transplant recipients has not been studied before.

Reduced renal function after liver transplantation (LT) is a long-term extrahepatic complication of major concern caused at least partly by calcineurin inhibitor nephrotoxicity. We report on long-term renal function after LT in children from a single center and analyze the usefulness of glomerular filtration rate (GFR) estimation methods in the follow-up of pediatric LT patients.

Hepatobiliary cystadenomas and cystadenocarcinomas are rare tumors. Differentiating between these tumors and benign hepatic cysts may be difficult. Because of their rarity, diagnosis is often delayed and may result in inaccurate treatment, resulting in unnecessary morbidity and mortality. The purpose of this report is to draw attention to these entities and their complications. We report on two cases with spontaneous rupture of hepatobiliary cystadenoma and cystadenocarcinoma cysts, initially treated as simple hepatic cysts by aspiration, or by aspiration combined with sclerotherapy. The spontaneous rupture of the cysts appeared years after the initial treatment of the cysts, leading in one case to a prolonged stay in an intensive care unit. In both cases, a formal liver resection was carried out and microscopic investigations revealed a mucinous cystadenocarcinoma and cystadenoma. In conclusion, although hepatobiliary cystadenomas and cystadenocarcinomas are rare findings, they should not be forgotten in the diagnostic workshop when examining patients with hepatic cysts. If hepatobiliary cystadenomas and cystadenocarcinomas cannot be excluded following radiological imaging, surgery is recommended.

We studied the role of endogenous activated protein C (APC), the major physiological anti-coagulant with concomitant anti-inflammatory properties, on ischemia/reperfusion (I/R) in 45 patients participating in a larger trial comparing three immunosuppressive protocols in cadaveric renal transplantation: perioperative anti-thymocyte globulin (ATG, Fresenius AG, Bad Homburg, Germany), perioperative basiliximab and conventional triple therapy. Blood samples for assessing plasma APC, protein C, and lactoferrin concentrations, neutrophil CD11b and L-selectin expressions and blood leukocyte differential counts were obtained preoperatively and before reperfusion from central venous cannula, complemented with simultaneous samples from iliac artery and graft vein for calculation of transrenal differences (Δ) of study parameters at 1 and 5 min after reperfusion. Unlike basiliximab or conventional therapy groups, ATG infusion induced a substantial increase in plasma APC concentration (119 [88–144]% before infusion vs. 232 [85–1246]% after infusion, p < 0.001), resulting in renal graft sequestration of APC at 1 min after reperfusion (Δ=−72 [−567 to 12]%, p < 0.001). Graft APC consumption was associated with transrenal reduction of neutrophil activation markers (L-selectin r= 0.7, p = 0.01; lactoferrin r=−0.6, p = 0.02; CD11b r=−0.8, p = 0.001), and with both warm (r= 0.6, p = 0.01) and cold ischemia time (r= 0.6, p = 0.02) and donor age (r= 0.6, p = 0.01). These findings suggest that APC has an anti-inflammatory role in I/R injury in clinical renal transplantation.

We studied the role of endogenous activated protein C (APC), the major physiological anti‐coagulant with concomitant anti‐inflammatory properties, on ischemia/reperfusion (I/R) in 45 patients participating in a larger trial comparing three immunosuppressive protocols in cadaveric renal transplantation: perioperative anti‐thymocyte globulin (ATG, Fresenius AG, Bad Homburg, Germany), perioperative basiliximab and conventional triple therapy. Blood samples for assessing plasma APC, protein C, and lactoferrin concentrations, neutrophil CD11b and L‐selectin expressions and blood leukocyte differential counts were obtained preoperatively and before reperfusion from central venous cannula, complemented with simultaneous samples from iliac artery and graft vein for calculation of transrenal differences (Δ) of study parameters at 1 and 5 min after reperfusion. Unlike basiliximab or conventional therapy groups, ATG infusion induced a substantial increase in plasma APC concentration (119 [88–144]% before infusion vs. 232 [85–1246]% after infusion, p < 0.001), resulting in renal graft sequestration of APC at 1 min after reperfusion (Δ=−72 [−567 to 12]%, p < 0.001). Graft APC consumption was associated with transrenal reduction of neutrophil activation markers (L‐selectin r= 0.7, p = 0.01; lactoferrin r=−0.6, p = 0.02; CD11b r=−0.8, p = 0.001), and with both warm (r= 0.6, p = 0.01) and cold ischemia time (r= 0.6, p = 0.02) and donor age (r= 0.6, p = 0.01). These findings suggest that APC has an anti‐inflammatory role in I/R injury in clinical renal transplantation.

The authors studied the impact of neutrophil activation, detected in experimental models, on reperfusion injury in clinical renal transplantation.

Activated protein C (APC) exhibits anticoagulant and antiinflammatory properties. We studied the kinetics and magnitude of protein C activation in clinical liver transplantation and the interaction of this activation with neutrophil and monocyte activation.

AbstractWe studied the effect of initial graft function and acute rejection on graft survival in 1047 cadaveric renal transplantations during 1991–1997 with a constant policy of donor selection, graft allocation, and immunosuppression. The overall 1‐and 5‐year patient survival rates were 96% and 88%, and the 1‐ and 5‐year graft survival (GS) rates were 92% and 78%. Delayed graft function (DGF) occurred in 31% and there were 1.2% never‐functioning grafts. One‐year GS in transplantations with early graft function (EGF) was 95% compared to 87% in DGF (P< 0.001). Donor age and cause of death, type of graft perfusion and cold ischemia time, and type and length of dialysis treatment were significant factors in determining the onset of graft function. These factors did not have a significant direct effect on GS. Early (< 100 days) acute rejection occurred in 25%. In transplantations without rejection, the 1 and 5‐year GS was 93.3% and 80.8%. In acute rejection responding to steroids, the GS was equal to that up to 3 years, but after that a significantly worse survival rate was observed (1‐ and 5‐year GS: 93.6% and 73.4 %). DGF was detrimental to GS both in transplantations without rejection and in all rejection types.

Background: Heavy alcohol consumption is associated with menstrual irregularities, including anovulation, luteal‐phase dysfunction, recurrent amenorrhea, and early menopause. In addition, moderate to heavy alcohol intake has been found to increase the risk of spontaneous abortions and breast cancer. These adverse effects could at least in part originate from alcohol‐mediated changes in hormone levels.

Background & Aims:Oxygen free radicals, generated by xanthine oxidase (XO) and activated leukocytes, are involved in reperfusion injury in experimental liver transplantation. The roles of XO and neutrophil activation during reperfusion in clinical liver transplantation were studied. Methods:In 10 patients undergoing liver transplantation, we assessed plasma concentrations of circulating XO by enzyme-linked immunosorbent assay (ELISA), the purine metabolites hypoxanthine, xanthine, and urate by high-performance liquid chromatography, lactoferrin by ELISA, and malondialdehyde fluorometrically up to 48 hours postoperatively. Results:During reperfusion after portal vein declamping, elevated plasma concentrations of XO (52.1 ng/mL [range, 8.0–440.1]), hypoxanthine (81.62 μmol/L [48.2–108.7]), xanthine (21.01 μmol/L [8.7–22.3]), and lactoferrin (532.6 ng/mL [370.4–1326.6]) were observed compared with the preoperative levels (0 ng/mL [0–12], 1.88 μmol/L [0.62–3.15], 0.95 μmol/L [0–0.41], and 164.3 ng/mL [73.7–334.1], respectively; all P< 0.05). No changes occurred in urate or malondialdehyde. After portal vein declamping, XO, hypoxanthine, and xanthine levels were substantially greater in the hepatic than portal vein (all P< 0.05). Marginal transhepatic differences occurred in lactoferrin. Conclusions:Reperfusion during liver transplantation is associated with liberation of xanthine oxidase, hypoxanthine, and xanthine from the liver into the circulation. During reperfusion, intravascular neutrophil activation takes place in the hepatic circulation.

Rat models are often used to study liver allograft rejection. We have established a model for rat liver allograft rejection, monitored by fine needle aspiration biopsy (FNAB), in the strain combination PVG-to-BN with a mean survival time of 37 ± 20 days. In this model, we observed acute rejection with an intense peak of lymphoid blasts and lymphocyte-dominated inflammation in the FNAB [9.1 ± 3.0 corrected increment units (CIU)], and an eventual increase in macrophages (up to 4.2 ± 4.4 CIU), together with fibrosis and parenchymal necrosis in the graft. Markers of immune activation, such as an increase in IL-2-receptor (from 1 % ± 2 % to 21 % ± 13 %) and class II (from 20 % ± 9 % to 43 % ± 13 %) expressing lymphoid cells and induction of ICAM-1 in the graft, were consistent with the overall cellular response. The FNAB correlated well with parallel graft histology. In this rat model, the atraumatic monitoring makes a close follow-up possible without having to sacrifice the experimental animals. This saves work, animals, and costs in the study of liver rejection.

We prospectively studied anatomical variations and diseases of the liver in 100 consecutive donor operations during a period of 1 year. The “normal” arterial anatomy with a single hepatic artery (HA) from the celiac trunk was seen in 76% of all cases. Seven of twelve different major variations of the HA may be considered as “rare”, one of which cannot be found in the earlier literature. During harvesting, 6% of the livers were discarded, 3% on the basis of infection and 1% because of a polycystic disease. Two cases were rejected as the liver was found to be severely hypoperfused or hypoxic in an otherwise stable donor. Severe steatosis was macroscopically and histologically diagnosed in 3% of the cases, and in three donors a benign tumour was found in the liver or in the gall bladder. Two primarily nonfunctioning livers in the present series of 94 recipient operations were retrieved from this group of severely steatotic livers. As the donor liver was totally “normal” in only 2 out of 3 of the cases, the present study underlines the importance of searching for extremely variable anomalies of the HA and for liver-related diseases during organ harvesting.

We have used allogeneic pig liver transplants to investigate the structure of inflammation in acute liver allograft rejection. An inflammatory episode of acute cellular rejection was observed in 9/10 allografts in non-immunosuppressed recipients, when monitored with simultaneous fine-needle aspiration biopsies (FNAB) and core needle biopsies (NB). The intensity of inflammation in FNAB was quantitated using the corrected increment method and correlated with NB findings. In FNAB, all inflammatory episodes were detected on the 4th day after transplantation with lymphoid blast and lymphocyte infiltration, later accompanied by monocytes and macrophages. Maximal intensity of inflammation was recorded in FNAB on day 14. In NB, histology demonstrated distinct inflammation in the portal area on day 4. The predominantly lymphocytic infiltration, also containing varying numbers of plasma cells, eosinophils, neutrophils and macrophages, reached its maximum 7–14 days after transplantation. With the indirect immunoperoxidase technique, lymphoid cell subpopulation analysis of FNAB demonstrated an increase of both T4 and T8 cells during rejection. The T4/ T8 ratio was first low, and increased at the beginning of the episode, on day 4, but decreased again on days 7 and 14. The number of B cells in the graft was also elevated during rejection. The cellular changes in the corresponding blood specimens followed approximately the same lines, although the changes were less prominent. NB immunohistology, using immunoperoxidase and frozen sections, correlated well with FNAB results, and demonstrated a T4 predominance in the portal area on day 4 but a T8 predominance on days 7 and 14. In addition to lymphoid cells, macrophages/granulocytes were also frequent in the portal area and scattered in the parenchyma on days 7 and 14. An additional inflammatory cell component in liver allograft rejection, detectable only in the NB, was eosinophils in the portal area, recorded in maximum on day 14. Taken together, the inflammatory changes in the FNAB and NB were similar, and time-related changes of cellular infiltrate in FNAB and NB correlated closely.

The procedure of liver transplantation in alcoholic liver disease raises the question whether it would be possible to regulate the recipient's future drinking by the choice of donor liver. To address this question, we conducted transplantations with rat lines selected for high (AA) and low (ANA) alcohol preference. AA recipients having alcohol experience before the operation remained heavy drinkers regardless of whether the graft came from an AA or ANA donor. However, in those AA recipients who started drinking only after the operation, differences emerged, with AA grafts creating heavy drinking and ANA donor livers resulting in very low drinking. An overall increase in the acetaldehyde levels was introduced by the ANA livers, thus reflecting the original line differences. Similarly, in subsequent experiments, it was observed that when the aldehyde dehydrogenase inhibitor calcium carbimide was introduced in different amounts to the diet, alcohol drinking was reduced more in animals not used to drinking. The magnitude of this effect, especially in situations with established heavy drinking, is of relevance in future contemplations about liver transplantations between humans with dfferent aldehyde dehydrogenase genotypes.