To evaluate a new 2-step technique for obtaining adequate but short-term parenchymal hypertrophy in oncologic patients requiring extended right hepatic resection with limited functional reserve.Patients presenting with primary or metastatic liver tumors often face the dilemma that the remaining liver tissue may not be sufficient. Preoperative portal vein embolization has thus far been established as the standard procedure for achieving resectability.Two-staged hepatectomy was performed in patients who preoperatively appeared to be marginally resectable but had a tumor-free left lateral lobe. Marginal respectability was defined as a left lateral lobe to body weight ratio of less than 0.5. In the first step, surgical exploration, right portal vein ligation (PVL), and in situ splitting (ISS) of the liver parenchyma along the falciform ligament were performed. Computed tomographic volumetry was performed before ISS and before completion surgery.The study included 25 patients with primary liver tumors (hepatocellular carcinoma: n = 3, intrahepatic cholangiocarcinoma: n = 2, extrahepatic cholangiocarcinoma: n = 2, malignant epithelioid hemangioendothelioma: n = 1, gallbladder cancer: n = 1 or metastatic disease [colorectal liver metastasis]: n = 14, ovarian cancer: n = 1, gastric cancer: n = 1). Preoperative CT volumetry of the left lateral lobe showed 310 mL in median (range = 197-444 mL). After a median waiting period of 9 days (range = 5-28 days), the volume of the left lateral lobe had increased to 536 mL (range = 273-881 mL), representing a median volume increase of 74% (range = 21%-192%) (P < 0.001). The median left lateral liver lobe to body weight ratio was increased from 0.38% (range = 0.25%-0.49%) to 0.61% (range = 0.35-0.95). Ten of 25 patients (40%) required biliary reconstruction with hepaticojejunostomy. Rapid perioperative recovery was reflected by normalization of International normalized ratio (INR) (80% of patients), creatinine (84% of patients), nearly normal bilirubin (56% of patients), and albumin (64% of patients) values by day 14 after completion surgery. Perioperative morbidity was classified according to the Dindo-Clavien classification of surgical complications: grade I (12 events), grade II (13 events), grade III (14 events, III a: 6 events, III b: 8 events), grade IV (8 events, IV a: 3 events, IV b: 5 events), and grade V (3 events). Sixteen patients (68%) experienced perioperative complications. Follow-up was 180 days in median (range: 60-776 days) with an estimated overall survival of 86% at 6 months after resection.Two-step hepatic resection performing surgical exploration, PVL, and ISS results in a marked and rapid hypertrophy of functional liver tissue and enables curative resection of marginally resectable liver tumors or metastases in patients that might otherwise be regarded as palliative.
Adipocytes synthesize galectin-3 whose deficiency protects from inflammation associated with metabolic diseases. We aimed to study circulating galectin-3 in obesity and type 2 diabetes (T2D).Galectin-3 was measured by ELISA in the serum of male normal-weight and overweight controls and T2D patients and in T2D patients of both sexes. Because visceral fat contributes to systemic inflammation, galectin-3 was analyzed in paired samples of human and rodent sc and visceral adipose tissue. Visceral adipose tissue adipokines are released to the portal vein, and galectin-3 was analyzed in portal, hepatic, and systemic venous serum (PVS, HVS, and SVS, respectively) of patients with liver cirrhosis and in patients who underwent surgery for nonhepatic diseases. The effect of metformin on adipocyte galectin-3 was analyzed by immunoblot.Circulating galectin-3 was similarly elevated in T2D and obesity compared with normal-weight individuals and revealed a body mass index-dependent positive correlation with leptin, resistin, IL-6, and age. In T2D patients, galectin-3 was increased in serum of patients with elevated C-reactive protein and negatively correlated with glycated hemoglobin. Metformin treatment was associated with lower systemic galectin-3. Reduced galectin-3 in metformin-incubated human adipocytes indicated that low galectin-3 may be a direct effect of this drug. Galectin-3 was higher in PVS compared with HVS and SVS, suggesting that the splanchnic region is a major site of galectin-3 synthesis. Low galectin-3 in HVS compared with PVS demonstrated hepatic removal.Systemic galectin-3 is elevated in obesity and negatively correlates with glycated hemoglobin in T2D patients, pointing to a modifying function of galectin-3 in human metabolic diseases.
To increase the number of transplanted organs, the Eurotransplant foundation uses a so-called “rescue-organ-allocation” procedure for organs that had been rejected by at least three consecutive transplant centers for medical reasons. The transplant center that finally accepts such an organ can then freely choose a patient from its own waiting list, without being bound to regular allocation criteria. Almost 30% of deceased donor livers are now allocated through this process in the Eurotransplant region. We report our results of 38 “rescue-allocation” livers (RA livers) transplanted at our institution (2003–2007), compared to a group of 115 regularly allocated organs within the same period. From our data, RA livers have the same results as regularly allocated livers. Type and frequency of postoperative morbidity did not differ between both groups, though the analysis of subgroups showed a tendency toward reduced survival of RA livers in patients with viral hepatitis. Interestingly, the Donor Risk Index (DRI) showed no difference between RA livers and regularly allocated livers. Although preliminary due to small numbers, we conclude that RA livers can be safely transplanted without increased mortality or morbidity. However, no donor specific criteria which would justify rejecting a RA liver were found. This highly challenges the applicability of the RA procedure in its current form.
Split liver transplantation (SLT) offers the potential for expanding the limited deceased donor pool. Whereas outcomes of SLT in the pediatric population are generally considered positively, there are concerns regarding increased complications, especially biliary problems of right-extend liver transplantation (ERLT).1,2 Limiting liver splitting to optimal donors using a standardized technique may enable equivalent results of ERLT and whole liver transplantation (WLT). The technique of partial liver transplantation was developed by R. Pichlmayr in the 1980s.3 After initial trials and a clinical learning curve, SLT was established in Germany as a standard procedure, applied in-situ by experienced transplant surgeons who either performed the splitting procedure in the donor clinic or, alternatively, the ex-situ application for liver transplants that were shipped to recipient hospitals. As a rule, during the initial period, both split grafts (right extended and left lateral) remained in the splitting center. Later, in early 2000, it was decided in Germany that the extended right graft will no longer be allocated to the splitting center but rather undergo a nationwide Model for End-stage Liver Disease (MELD)–based allocation to avoid a preference for centers or patients. This approach resulted in a second transport and thus a prolonged ischemic time. Notably, only highly selected organs of excellent quality are used for ERLT. On the background of a significant recent deterioration of available donors in Germany,4 we hypothesized that the outcome after ERLT from optimal donors should compare favorably to that of WLT. Particularly, we were interested in testing if the change in allocation policy leading to prolonged cold ischemic time (CIT) and possibly further organ damage in ERLT may affect transplant outcomes. Against this background, we conducted a retrospective study in 7 large transplant centers in Germany between 2007 and 2015. A 1:1 matched-pairs analysis of 121 patients with ERLT and WLT each was done. Matching criteria included (1) recipient age, (2) recipient calculated MELD score, and (3) donor age. Notably, ischemic times in the ERLT group increased by approximately 2.5 hours. Regarding surgical outcome, biliary and vascular complications were comparable following ERLT versus WLT. Likewise, overall patient mortality was comparable (17.4% with 21 patient deaths after ERLT and WLT each). Interestingly, in the early postoperative period (by 3 mo) patient mortality was higher after ERLT compared with WLT. With regard to the causes of death, organ failure with infectious complications, often associated with primary non function, dominated in the ERLT group. Additionally, statistical analysis revealed a significant reduction of graft survival for right-extended splits compared with whole organs (Figure 1). This difference in organ survival was distinctly amplified in the subgroup of patients transplanted with a high MELD score (≥30 points) (Figure 2).FIGURE 1.: Graft survival whole organ vs right-extended split liver transplantation (LT). The figure shows the graft survival of the matched-pairs cohort (whole organ vs right-extended split LT, n = 121 per group) illustrated by Kaplan-Meier survival curves. There was a significant reduced graft survival following right-extended split LT compared to whole liver transplantation (Log-rank test P = 0.046).FIGURE 2.: Graft survival whole organ vs right-extended split liver transplantation (LT) in recipients calculated MELD score ≥30 points. The figure illustrates the graft survival in patients with a high MELD score at the time of transplantation (MELD score ≥ 30 points; n = 52 patients). There was a clearly reduced graft survival following right-extended split LT compared to whole organ (Log-rank test P = 0.077). MELD, Model for End-stage Liver Disease.Liver allocation in Germany is based on urgency using the MELD score.5 In clinical practice, liver splitting (generally ex-situ) is performed by the transplant center for a small child as the primary recipient, if the graft quality is estimated of appropriate quality. There are no clearly defined splitting criteria or mandatory splitting policies for high-quality organs and also no incentives for the specific center performing liver graft splitting. The remaining right-extended graft then undergoes formal MELD allocation within Germany or in selected cases in the entire Eurotransplant region6 resulting into prolonged ischemic times. In our cohort, ERLT showed a worse graft survival than WLT resulting into higher early mortality in the ERLT group. In particular, ERLT recipients with high MELD scores demonstrated an increased risk of primary non function and early mortality. We postulate that the interplay of several factors may explain the inferior outcomes of ERLT observed in our study, despite the use of organs from high-quality donors. The graft quality decreases as the splitting procedure creates an anatomic variant graft. Further damage of the graft occurs due to prolonged CIT with an extended transport time due to the formal allocation of the ERLT graft. In detail, in our study, the mean CIT in ERLT was 2.5 hours above the CIT in WLT resulting into an average of 13 hours. As split liver transplants are more technically demanding, they are also more vulnerable to secondary hits such as prolonged CIT and postoperative complications in severely ill recipients.7 Because of these factors, the early postoperative period after SLT is most critical which seems to be particularly true for recipients with high MELD levels. In our opinion, it is essential to improve the logistics of SLT in Germany to reduce CITs. In a recent analysis of 64 adult recipients who received an ERLT at the University Medical Center Hamburg-Eppendorf,8 we found that grafts after external splitting with subsequent shipping to our center had a significantly longer ischemic time and compromised outcomes compared to ERLT after in-house splitting. Besides internal splitting with both split parts remaining in the same center, several other options could be considered: in situ splitting in the donor hospital followed by parallel shipping of split grafts to 2 recipient centers, sharing of splits within a regional network reducing travel distances for the second split, and, once established, the use of machine perfusion to abrogate the negative consequences of prolonged ischemic times. All of these options require adjustments with regard to legal, administrative, and logistical issues as well as human and hospital resources. However, at a time of organ shortage, when split liver transplants offer the opportunity to increase the number of transplants, every effort must be made to ensure the optimal outcome of these valuable transplants. In conclusion, with the introduction of MELD-based allocation of right-extended grafts causing long CITs outcomes have been inferior. As a result, liver splitting enables pediatric liver transplant but shows results that, because of the logistics implemented in Germany, are well below expectations that can be anticipated from these high-quality transplants—in our opinion, a tragedy at times when every effort should be made to increase organ availability and to improve outcomes.
