To analyze developing infections after living donor hepatectomy (LDH) in living liver donors (LLDs).

Demographic and clinical characteristics of 1106 LLDs were retrospectively analyzed in terms of whether postoperative infection development. Therefore, LLDs were divided into two groups: with (n = 190) and without (n = 916) antimicrobial agent use.

The median age was 29.5 (min-max: 18-55). A total of 257 (23.2%) infection attacks (min-max: 1-8) was developed in 190 (17.2%) LLDs. The patients with the infection that were longer intensive care unit (ICU) and hospital stays, higher hospital admissions, emergency transplantation, invasive procedures for ERCP, PTC biloma, and abscess drainage, and the presence of relaparatomies and transcystic catheters. Infection attacks are derived from a 58.3% hepatobiliary system, 13.2% urinary system, 6.6% surgical site, and 5.8% respiratory system. The most common onset symptoms were fever, abdominal pain, nausea, and vomiting. A total of 125 positive results was detected from 77 patients with culture positivity. The most detected microorganisms from the cultures taken are Extended-Spectrum β-lactamases (ESBL) producing Klebsiella pneumonia (16.8%) and Escherichia coli (16%), Methicillin-Resistant Staphylococcus aureus [(MRSA) (9.6%)], Methicillin-susceptible S aureus [(MSSA) (9.6%)], and Pseudomonas aeruginosa (8.8%), respectively. The average number of ICU hospitalization days was 3 ± 2 (min 1-max 30, IQR:1) and hospitalization days was 14 ± 12 (min 3-max 138, IQR: 8). All infection attacks were successfully treated. No patients died because of infection or another surgical complication.

Infections commonly observed infected biloma, cholangitis, and abscess arising from the biliary system and other nosocomial infections are the feared complications in LLDs. These infections should be managed multidisciplinary without delay and carefully.

Postoperative pain after living donor hepatectomy is significant. Postoperative coagulopathy may limit the use of epidural analgesia, the gold standard for pain control in abdominal surgery. The erector spinae plane block (ESPB) is a novel regional anesthesia technique that has been shown to provide effective analgesia in abdominal surgery. In this study, we examined the effect of continuous ESPB, administered via catheters, on perioperative opioid requirements after right living donor hepatectomies for liver transplantation.

We performed a retrospective cohort study in patients undergoing right living donor hepatectomy. Twenty-four patients who received preoperative ESPB were compared to 51 historical controls who did not receive regional anesthesia. The primary endpoint was the total amount of oral morphine equivalents (OMEs) required on the day of surgery and postoperative day (POD) 1.

Patients in the ESPB group required a lower total amount of OMEs on the day of surgery and POD 1 [141 (107-188) mg] compared the control group [293 (220-380) mg; P < .001].

The use of continuous ESPB significantly reduced opioid consumption following right living donor hepatectomy.

This study aimed to evaluate postoperative long-term liver restoration and splenic enlargement and their clinical significance in living donor liver transplantation. One hundred and sixteen donors who had donated livers more than 5 years previously accepted the invitation to participate in this study. The liver restoration rate and the splenic enlargement rate were calculated as the rate with respect to the original volume. The mean liver restoration rate was 0.99 ± 0.12 and older age was associated with a higher incidence for liver restoration rate <0.95 (P = .005), whereas type of donor operation was not. The donors with liver restoration rate <0.95 showed lower serum albumin levels than those with liver restoration rate ≥0.95. The mean splenic enlargement rate was 1.10 ± 0.16. Right lobe donors demonstrated higher splenic enlargement rate (1.14 ± 0.18) than left lobe/lateral segment donors (1.06 ± 0.13). In the donors with splenic enlargement rate ≥1.10, platelet count was not fully restored to the preoperative level. In conclusion, older age increases the risk for incomplete postoperative liver restoration, which may be associated with a decrease in albumin more than 5 years after donation. Right lobe donation poses a risk of splenic enlargement, which is associated with incomplete restoration of platelet count.

Multidetector computerized tomography (MDCT) is considered to be a fast noninvasive diagnostic technique for the evaluation of postoperative complications in patients with liver transplantation (LT). However, its role has not been fully established in the diagnosis for detecting complications after liver transplantation. The aim of this work was to evaluate the diagnostic performance of MDCT for detecting abdominal complications in the early and late periods after LT.

We retrospectively enrolled 75 patients who had undergone LT from March 2006 to January 2010, followed by MDCT from March 2006 to November 2017. Patients were divided into 2 groups according to the timing after LT: within the first 3 months (early period) or ≥3 months after LT (late period). We evaluated vascular, biliary, and other complications on MDCT. Angiography, endoscopic retrograde cholangiography, and percutaneous transhepatic cholangiography were used as reference standards.

We initially found 77 complications in 45 patients (60.0%) with the use of MDCT. After comparison with the reference standards, 83 complications were diagnosed in 49 patients (65.3%). Forty-seven complications (34 vascular, 10 biliary, 3 other complications) were diagnosed in 33 patients (44.0%) during the early period, and 36 complications (6 vascular, 20 biliary, 10 other complications) were detected in 27 patients (36.0%) in the late period. The sensitivity, specificity, and diagnostic accuracy of MDCT for diagnosing overall complications were, respectively, 93.6%, 90.2%, and 92.0% in the early period (for vascular complications: 97.1%, 92.6%, and 94.3%,; for biliary complications: 80.0%, 100%, and 97.7%) and 77.8%, 98.1%, and 89.8% in the late period (for vascular complications: 83.3%, 100%, and 98.9%; for biliary complications: 65.0%, 98.6%, and 90.9%).

Although MDCT in the late period should be interpreted with caution in patients with suspected biliary complication, MDCT is a reliable diagnostic technique for the identification of early and late abdominal complications after LT.

This study was performed to evaluate the incidence and clinical outcome of diaphragmatic hernia after living-donor right hepatectomy.

Three hundred thirty-six patients (202 men, 134 women; mean age, 37.6 years) who underwent abdominal computed tomography (CT) after right donor hepatectomy were enrolled in this study. The CT images and the electronic medical records were reviewed. We evaluated the associations between diaphragmatic hernia and patient characteristics.

Diaphragmatic hernia developed in 9 (2.7%) of 336 patients at a median time interval of 173 days (range, 98-488 days) after hepatectomy. In all 6 patients with available follow-up CT images, diaphragmatic hernia increased in size. Three patients presented with abdominal pain and underwent diaphragmatic repair. Diaphragmatic hernia was associated with older age but not with body mass index or sex.

Clinicians and radiologists should not overlook the possibility of diaphragmatic hernia after living-donor right hepatectomy, especially in old liver donors.

The right lobe of the liver is generally preferred for living donor liver transplantation in adult patients with end-stage liver disease. It is important to know the preoperative factors relating to the major postoperative complications. We therefore evaluated the possible risk factors for predicting postoperative complications in right lobe liver donors.

Data from 378 donors who had undergone right lobe hepatectomy at our center were evaluated retrospectively. The factors we evaluated included donor age, gender, body mass index (BMI), remnant liver volume, operation time, history of previous abdominal surgery, inclusion of the middle hepatic vein and variations in the portal and bile systems.

Of the 378 donors, 219 were male and 159 female. None of the donors died, but 124 (32.8%) donors experienced complications including major complications (Clavien scores III and IV) in 27 (7.1%). Univariate analysis showed that complications were significantly associated with male gender and higher BMI (P<0.05), but not with donor age, remnant liver volume, operation time, graft with middle hepatic vein, variations in the portal and bile systems and previous abdominal surgery (P<0.05). Multivariate logistic regression analysis showed that major complications were significantly associated with male gender (P=0.005) and higher BMI (P=0.029). Moreover, the Chi-square test showed that there were significant relationships between major complications and male gender (P=0.010, X2=6.614, df=1) and BMI >25 kg/m2 (P=0.031, X2=8.562, df=1). Of the 96 male donors with BMI >25 kg/m2, 14 (14.6%) with major complications had significantly smaller mean remnant liver volume than those (82, 85.4%) without major complications (32.50%+/-4.45% vs 34.63%+/-3.11%, P=0.029).

Male donors with BMI >25 kg/m2 and a remnant liver volume ≤32.50% had a significantly increased risk for major complications.

For many patients, living donor liver transplantation represents their only hope of receiving a lifesaving graft. In certain (albeit rare) cases, a minor will be the only suitable donor. Living liver donation by minors has been reported in several countries. In the academic literature and professional guidelines, little attention is paid to the development of an ethical framework for this practice. The focus is frequently limited to the donation of regenerative tissues and kidneys. However, liver donation differs in important respects because of the increased medical risks and the lack of substitute therapies. Therefore, in this article, we assess whether living liver donation by minors is ethically appropriate. We argue that living liver donation by minors is justifiable only if minors possess the capacity to consent to donation or if the procedure is in their best interests. Although minors may possess adult-like levels of cognitive maturity, they lack sufficient psychosocial maturity to give valid consent to donation. In addition, living liver donation is generally not in a minor's best interests. With respect to the latter, the potential psychological benefits that a minor may experience as a result of living liver donation are insufficiently empirically supported and are unlikely to outweigh the short- and long-term medical and psychological risks. Therefore, we conclude that minors should not be considered as potential living liver donors.

Living donor liver transplantation (LDLT) has become necessary because of the shortage of cadaveric organs. We retrospectively analyzed 500 living donor hepatectomies using the Clavien classification system for complications to grade their severity.

We retrospectively identified and applied the Clavien classification to 500 consecutive donors who underwent right for LDLT left hepatectomy between January 2007 and August 2011.

The 149 complications were observed in 93 of 500 (18.6%) donors who were followed for a mean 30 months. There wan no donor mortality. Complications developed in 85 (18.6%) right 5 (35.7%) left, and 3 (10%) left lateral segment hepatectomy donors. The overall incidence of reoperations was 7.2%. Seventy-seven of 149 complications were grade I (51.6%) or 9 grade II (6%). The major complications consisted of 27 (18.1%) grade IIIa, 35 (23.4%) grade IIIb, and 1 (0.6%) grade IVa. Grade IVb and grade V complications did not occur. The most common problems were biliary complications in 14 of 181 donors (7.7%).

Donors for LDLT experienced a range of complications.

To study diagnostic laparoscopy as a tool for excluding donors on the day of surgery in living donor liver transplantation (LDLT).

This study analyzed prospectively collected data from all potential donors for LDLT. All of the donors were subjected to a three-step donor evaluation protocol at our institution. Step one consisted of a clinical and social evaluation, including a liver profile, hepatitis markers, a renal profile, a complete blood count, and an abdominal ultrasound with Doppler. Step two involved tests to exclude liver diseases and to evaluate the donor's serological status. This step also included a radiological evaluation of the biliary anatomy and liver vascular anatomy using magnetic resonance cholangiopancreatography and a computed tomography (CT) angiogram, respectively. A CT volumetric study was used to calculate the volume of the liver parenchyma. Step three included an ultrasound-guided liver biopsy. Between November 2002 and May 2009, sixty-nine potential living donors were assessed by open exploration prior to harvesting the planned part of the liver. Between the end of May 2009 and October 2010, 30 potential living donors were assessed laparoscopically to determine whether to proceed with the abdominal incision to harvest part of the liver for donation.

Ninety-nine living donor liver transplants were attempted at our center between November 2002 and October 2010. Twelve of these procedures were aborted on the day of surgery (12.1%) due to donor findings, and eighty-seven were completed (87.9%). These 87 liver transplants were divided into the following groups: Group A, which included 65 transplants that were performed between November 2002 and May 2009, and Group B, which included 22 transplants that were performed between the end of May 2009 and October 2010. The demographic data for the two groups of donors were found to match; moreover, no significant difference was observed between the two groups of donors with respect to hospital stay, narcotic and non-narcotic analgesia requirements or the incidence of complications. Regarding the recipients, our study clearly revealed that there was no significant difference in either the incidence of different complications or the incidence of retransplantation between the two groups. Day-of-surgery donor assessment for LDLT procedures at our center has passed through two eras, open and laparoscopic. In the first era, sixty-nine LDLT procedures were attempted between November 2002 and May 2009. Upon open exploration of the donors on the day of surgery, sixty-five donors were found to have livers with a grossly normal appearance. Four donors out of 69 (5.7%) were rejected on the day of surgery because their livers were grossly fatty and pale. In the laparoscopic era, thirty LDLT procedures were attempted between the end of May 2009 and October 2010. After the laparoscopic assessment on the day of surgery, twenty-two transplantation procedures were completed (73.4%), and eight were aborted (26.6%). Our data showed that the levels of steatosis in the rejected donors were in the acceptable range. Moreover, the results of the liver biopsies of rejected donors were comparable between the group A and group B donors. The laparoscopic assessment of donors presents many advantages relative to the assessment of donors through open exploration; in particular, the laparoscopic assessment causes less pain, requires a shorter hospital stay and leads to far superior cosmetic results.

The laparoscopic assessment of donors in LDLT is a safe and acceptable procedure that avoids unnecessary large abdominal incisions and increases the chance of achieving donor safety.

We compared the effect of two inhalation anesthetics desflurane and isoflurane on postoperative hepatic and renal functions as well as coagulation profiles in living donors undergoing right hepatectomy. This study was performed on 80 patients who were randomly allocated to group D (desflurane, n = 40) or group I (isoflurane, n = 40) after Faculty Ethics Committee approval. After induction, isoflurane or desflurane was used with air/oxygen for anesthetic maintenance. The isoflurane or desflurane concentration was set at one minimum alveolar concentration (MAC). Remifentanil was infused for analgesia as well as cisatracurium. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), international normalized ratio (INR), albumin, total bilirubin, blood urea nitrogen, creatinine, platelet count, and hemoglobin levels were analyzed preoperatively at end of the operation, and on postoperative days (PODs) 1, 2, 3, 5, 7, and 30. Both AST and ALT differed significantly and continually except on POD 30. AST showed significant elevations from the end of the operation to POD 2 and ALT, from the end of the operation to POD 5 in group I compared with group D. INR was significantly higher from the end of the operation to POD 3 in group I and to POD 2 in group D. At the end of the operation as well as on POD 1 and POD 2, INR was significantly increased in group I compared with group D. Albumin level was significantly lower at the end of the operation in both groups, but it was not different. No patient developed hepatic or renal failure. Our study showed better postoperative hepatic tests and INR using desflurane than isoflurane at equivalent doses of 1 MAC in living donors undergoing right hepatectomy.

Lee et al. recently published a method for estimating right hemi-liver volume (RHLV) by using bedside ultrasound measurement of right (R) and left (L) portal vein (PV) diameters and Urata's standard liver volume (SLV) formula where RHLV = SLV×[R(2) /(R(2) +L(2) )]. We calculated RHLV by substituting SLV from 15 different published formulas in the worldwide literature. We also modified Lee's method using right anterior (RA) and posterior (RP) where RHLV = SLV×[(RA(2) +RP(2) )/(RA(2) +RP(2) +L(2) )] for donors with unusual PV branching. We compared the calculated RHLV with RHLV estimated with software-assisted CT (SACT) volumetry and actual graft weight after right-lobe donation in 200 right-lobe donors. This study confirmed that accurate estimates of RHLV can be achieved by SACT volumetry or by the simple method of Lee but using the SLV of only 3 of the 15 published formulas (Lin or Vauthey using body weight or body surface area) rather than Urata's. Our modification of the Lee's formula using RA and RP, PV diameters was also accurate and not different from Lee's formula. These simplified formulas may be used for donor screening for graft size adequacy before expensive evaluation proceeds.

We sought to estimate the risk of perioperative mortality or acute liver failure for live liver donors in the United States and avoid selection or ascertainment biases and sample size limitations.

We followed up 4111 live liver donors in the United States between April 1994 and March 2011 for a mean of 7.6 years; deaths were determined from the Social Security Death Master File. Survival data were compared with those from live kidney donors and healthy participants of the National Health and Nutrition Examination Survey (NHANES) III.

Seven donors had early deaths (1.7 per 1000; 95% confidence interval [CI], 0.7-3.5); risk of death did not vary with age of the liver recipient (1.7 per 1000 for adults vs 1.6 per 1000 for pediatric recipients; P = .9) or portion of liver donated (2.0 per 1000 for left lateral segment, 2.8 per 1000 for left lobe, and 1.5 per 1000 for right lobe; P = .8). There were 11 catastrophic events (early deaths or acute liver failures; 2.9 per 1000; 95% CI, 1.5-5.1); similarly, risk did not vary with recipient age (3.1 per 1000 adult vs 1.6 per 1000 pediatric; P = .4) or portion of liver donated (2.0 per 1000 for left lateral segment, 2.8 per 1000 for left lobe, and 3.3 per 1000 for right lobe; P = .9). Long-term mortality of live liver donors was comparable to that of live kidney donors and NHANES participants (1.2%, 1.2%, and 1.4% at 11 years, respectively; P = .9).

The risk of early death among live liver donors in the United States is 1.7 per 1000 donors. Mortality of live liver donors does not differ from that of healthy, matched individuals over a mean of 7.6 years.

Organ transplantation from deceased donors is still far below the need. Because of this deficiency, liver transplantations are performed mostly from live donors in many transplant centers in our country. Living-donor liver transplantation (LDLT) has evolved dramatically over the past decade. The aim of this study was to present our clinical experience with living-donor hepatectomy.

We retrospectively analyzed all patients who underwent donor hepatectomy between March 2000 and September 2010. We reviewed demographic data, operation type, operation and cold ischemia times, duration of hospital stay, and postoperative complications.

During the study period, 140 living donors underwent operations for liver transplantation. We performed 108 right hepatectomies, 17 left hepatectomies, and 15 left lateral hepatectomies. The mean age of the donors was 30.8 years. There was no operative or postoperative mortality. Overall morbidity rate was 13.57% (n = 19). Nine patients had biliary leakages, 4 biliomas; 2 urinary tract infections, and 1 each inferior vena caval injury, pneumonia, portal vein thrombosis, and acute tubular necrosis. Reoperation was not required in any of these patients.

Living-donor liver transplantation is a valuable alternative for patients awaiting a cadaver organ. Live-donor hepatectomy can be performed with low morbidity. The greatest disadvantage of this procedure is the risk of the surgical operation for the individual who will experience no medical benefit from this procedure.

Right lobe living donor liver transplantation is an effective treatment for selected individuals with end-stage liver disease. Although 1 year donor morbidity and mortality have been reported, little is known about outcomes beyond 1 year. Our objective was to analyze the outcomes of the first 202 consecutive donors performed at our center with a minimum follow-up of 12 months (range 12-96 months). All physical complications were prospectively recorded and categorized according to the modified Clavien classification system. Donors were seen by a dedicated family physician at 2 weeks, 1, 3 and 12 months postoperatively and yearly thereafter. The cohort included 108 males and 94 females (mean age 37.3 +/- 11.5 years). Donor survival was 100%. A total of 39.6% of donors experienced a medical complication during the first year after surgery (21 Grade 1, 27 Grade 2, 32 Grade 3). After 1 year, three donors experienced a medical complication (1 Grade 1, 1 Grade 2, 1 Grade 3). All donors returned to predonation employment or studies although four donors (2%) experienced a psychiatric complication. This prospective study suggests that living liver donation can be performed safely without any serious late medical complications and suggests that long-term follow-up may contribute to favorable donor outcomes.

We compared postoperative hepatic and renal functions between the two inhalational anesthetics, desflurane and sevoflurane in living donors undergoing right hepatectomy. Seventy-four adult donors were randomly allocated into Des group (n = 37) and sevo group (n = 37). Before the induction of anesthesia, morphine sulfate 400 microg was injected intrathecally. Anesthesia was maintained with one minimum alveolar concentration (MAC) of deflurane or sevoflurane plus continuous intravenous remifentanil. Liver and renal function tests were performed and analysed at preoperative period, immediately after operation, and on 1st, 2nd, 3rd, 5th, 7th, and 30th postoperative days (PODs). Aspartate aminotransferase (AST) showed significant elevations from the day of surgery to POD 3 and alanine aminotransferase (ALT) was significantly elevated on POD 1 and POD 3 in the sevo group. Albumin level was significantly lower on POD 2 in the sevo group. Creatinine was significantly higher on POD 3 and POD 30 and estimated glomerular filtration ratio was significantly lower on POD 3 and POD 30 in the sevo group. No patient developed hepatic or renal failures. The results of our study showed better postoperative hepatic and renal function test with desflurane than sevoflurane at equivalent dose of 1 MAC in living donors undergoing right hepatectomy, but further study is required to evaluate clinical importance.

Living donor liver transplantation (LDLT) has been expanding to adult recipients by using right lobe grafts. However, the incidence of complications is more frequent than that involving left lobe grafts. Hence, we aimed to analyze postoperative complications in right lobe liver donors as a step to improve the results in the donors.

Three hundred and eleven right lobe liver donors were retrospectively reviewed between February 1998 and December 2003.

The ages of the donors ranged from 19 to 64 years (median: 46 years). Their body mass index ranged from 16.6 to 34.3 (median: 22.1). The mean duration of the operation was 6.58 (1.25) hours and blood loss was 289 (254) mL. The estimated median donor residual liver volume was 42.2% (range: 20.6-60.3%) and the median hospital stay was 14.5 days (range: 6-267 days). One donor died of liver failure due to small residual liver volume (26%) and steatohepatitis. One hundred and twenty three complications occurred in 104 donors (33.4%). Donors experienced one or more complications. According to the Clavien classification, grade I complications occurred in 71 of the episodes (57.7%), grade II complications in 9 (7.3%), grade IIIa complications in 39 (31.7%), grade IIIb complications in 3 (2.5%), and grade V complications in 1 (0.8%). Biliary complications were the most common and occurred in 37 donors (12%).

Right lobe liver donation is a widely accepted procedure that results in the expansion of the indication for LDLT to adults and large children. However, remnant liver size and anatomical variations in the biliary tree represent important risk factors for postoperative complications.

Living donor liver transplantation (LDLT) has been expanding to adult recipients by using right lobe grafts. However, the incidence of complications is more frequent than that involving left lobe grafts. Hence, we aimed to analyze postoperative complications in right lobe liver donors as a step to improve the results in the donors.

Three hundred and eleven right lobe liver donors were retrospectively reviewed between February 1998 and December 2003.

The ages of the donors ranged from 19 to 64 years (median: 46 years). Their body mass index ranged from 16.6 to 34.3 (median: 22.1). The mean duration of the operation was 6.58 (1.25) hours and blood loss was 289 (254) mL. The estimated median donor residual liver volume was 42.2% (range: 20.6-60.3%) and the median hospital stay was 14.5 days (range: 6-267 days). One donor died of liver failure due to small residual liver volume (26%) and steatohepatitis. One hundred and twenty three complications occurred in 104 donors (33.4%). Donors experienced one or more complications. According to the Clavien classification, grade I complications occurred in 71 of the episodes (57.7%), grade II complications in 9 (7.3%), grade IIIa complications in 39 (31.7%), grade IIIb complications in 3 (2.5%), and grade V complications in 1 (0.8%). Biliary complications were the most common and occurred in 37 donors (12%).

Right lobe liver donation is a widely accepted procedure that results in the expansion of the indication for LDLT to adults and large children. However, remnant liver size and anatomical variations in the biliary tree represent important risk factors for postoperative complications.

Living donor liver transplantation (LDLT) has been accepted as a valuable treatment for patients with end-stage liver disease seeking to overcome the shortage of organs and the waiting list mortality. The aim of this study was to report our experience with LDLT.

We retrospectively analyzed 50 LDLTs performed in our organ transplant center from January 1997 to March 2008. We reviewed the demographic data, family history, operative and hospital stay durations as well as postoperation complications among donors and recipients. We also performed a retrospective analysis of recipient chemical and biochemical data.

Among 50 patients (30 males and 20 females) of overall mean age of 7.21 +/- 5.35 who underwent LDLT (10 right lobe, 38 left lobe, and 2 left lateral segments), 47 received a liver graft from their parent, two from a brother, and one from an uncle. The most common indications for LDLT were end-stage liver disease due to Wilson's disease (16%), cryptogenic cirrhosis (16%), tyrosinemia (14%), biliary atresia (12%), autoimmune hepatitis (12%), and progressive familial intrahepatic cholestasis (12%). The mean follow-up was 16.91 +/- 23.74 months. There were 13 (26%) recipient mortalities including vascular complications; three to sepsis after bowel perforation, two from liver dysfunction, two from chronic rejection due to noncompliance, and one from diffuse aspergillosis. The morbidity rate was 50%, including 19 reexplorations during the hospital course and five biliary complications.

This study demonstrated that LDLT can decrease the number of patients awaiting liver transplantation especially in the pediatric group. However, because of relatively high mortality and morbidity, we must improve our treatment outcomes.

Living donor liver transplantation in adults continues to be controversial. Viewed as an alternative to prevent deaths on the waiting list, this type of transplant is the only possibility in Asian countries (Japan, Korea, China, etc) but is not widely applied in the west. This intervention is associated with significant donor morbidity (depending on the scale of the intervention) and mortality which, although sporadic, reduces its acceptance, especially in a context with high cadaveric donation. Outcomes in recipients are similar to those in cadaveric transplant recipients, although the high incidence of biliary complications could compromise long-term results. We describe the experience of Hospital Clínic in a total of 67 transplant recipients. Graft and patient survival at 1 and 5 years was 90.7%, 70.3%, 90.7% and 77.6%, respectively. Although the frequency of biliary complications was high (37.3%), death from sepsis and retransplantation only occurred in two patients.

The healthy condition of living donors makes their tolerance to pain particularly low, and clinicians are often challenged to come up with an analgesic technique that is effective yet ensures donor safety. This study compared, in donor right hepatectomy, the efficacy and safety of preoperative intrathecal morphine (ITM) combined with intravenous patient-controlled analgesia (IV-PCA) with IV-PCA alone. Forty adult patients were randomly allocated into 2 groups: ITM+IV-PCA group (n = 20) and IV-PCA-only group (n = 20). Patients in the ITM+IV-PCA group received morphine sulfate (400 microg). The visual analog scale (VAS) at rest and when coughing and supplementary meperidine and IV-PCA (fentanyl) consumption were assessed at 2, 4, 6, 8, 10, 12, 18, 24, 30, 36, 42, 48 56, 64, and 72 hours after surgery. Also, side effects such as sedation, dizziness, nausea, vomiting, pruritus, and respiratory depression were evaluated. The ITM+IV-PCA group showed significantly less pain at rest and when coughing for up to 30 hours and 24 hours, respectively. Cumulative postoperative consumption of meperidine and IV-PCA (fentanyl) were significantly less in the ITM+IV-PCA group. The incidence of side effects were comparable between the 2 groups except for pruritus; its incidence was significantly higher in the ITM+IV-PCA group during the first 24 hours, but no treatment was required due to its mild severity. The results of our study suggest that preoperative ITM combined with IV-PCA may be considered as an effective and safe pain management regimen in living liver donors who have characteristics of low tolerance to pain and postoperative coagulation derangement.

Various volatile anesthetics have been used in hepatectomy in living donors, and their effects on major organs have been extensively evaluated. However, the impact of total intravenous anesthesia (TIVA) on postoperative liver and renal functions after large liver resections has been less extensively investigated than that of volatile agents. The aim of this study was to compare the postoperative hepatic and renal functions between volatile anesthesia with desflurane and TIVA with propofol-remifentanil in living donors undergoing right hepatectomy. Seventy adult patients were randomly allocated into 2 groups: the desflurane group (n = 35) and TIVA group (n = 35). Aspartate aminotransferase, alanine aminotransferase, prothrombin time (PT), albumin, total bilirubin (TB), blood urea nitrogen (BUN), creatinine (Cr), BUN/Cr ratio, estimated glomerular filtration rate (GFR), platelet count, and hemoglobin levels were analyzed in the preoperative period, immediately after the operation, and on the first, second, third, fifth, seventh, and thirtieth postoperative days (PODs). Most of the liver function test results were not significantly different between the 2 groups. However, PT (international normalized ratio) and TB were significantly greater on POD 5 in the TIVA group. Among the renal function tests, Cr was significantly higher and estimated GFR was significantly lower on POD 1 in the TIVA group. The platelet counts and hemoglobin levels were similar between the 2 groups. In conclusion, the results of our study suggest that living related donors for liver transplant may have a better outcome following anesthesia with desflurane. However, further testing will be necessary to prove this hypothesis.

With the increasing number of living donor liver transplantations, biliary complications in donors have emerged as a major postoperative problem. The aim of the present study was to characterize the features of the biliary complications that occur in donors.

The study subjects comprised 731 consecutive patients who donated liver grafts (434 right-lobe and 297 left-lobe grafts) for transplantation at Kyoto University Hospital from July 1999 to December 2006. Donors whose biliary complications could not be cured by conservative therapy were referred for endoscopic treatment.

Postoperative biliary complications occurred in 55 (7.5%) donors. Initially, 48 of these 55 donors had biliary leakage and 7 had biliary stricture. Subsequently, 5 of 48 donors with leakage developed biliary stricture. The respective incidences of biliary leakage and overall biliary complications were significantly higher among donors of right-lobe grafts (9.9% and 11.1%) than among donors of left-lobe grafts (1.7% and 2.4%). Among 55 donors with biliary complications, 24 were cured by conservative therapy, and 1 was converted to surgical repair due to ileus. Endoscopic treatment was successful in 24 of 30 (80%) donors treated by endoscopic retrograde cholangiography, while the remaining 6 (20%) patients underwent surgery due to difficulties with cannulation (N = 2), excessive biliary leakage (N = 2), or complete biliary obstruction (N = 2).

Donors of right-lobe grafts have a significantly higher incidence of biliary complications than donors of left-lobe grafts. When conservative therapy fails, endoscopic treatment is effective for these complications, and should be attempted as the first-line therapy before surgical repair.

Donor safety has been scrutinized by both the medical community and the media. Variability exists in reported donor complications and associated risk factors are ill defined. Use of administrative data can overcome the bias of single-center studies and explore variables associated with untoward events. A retrospective cohort study identifying living liver donors in two large healthcare registries yielded 433 right and left lobe donors from 13 centers between 2001 and 2005. Perioperative complications were identified using International Classification of Diseases, 9th Revision (ICD-9) coding data and classified according to the Clavien system. Logistic regression models identified factors associated with complications. There was one perioperative death (0.23%). The overall complication rate was 29.1% and major complication rate defined by a Clavien grade >or=3 was 3.5%. Center living-donor volume (OR = 0.97, 95% CI = 0.95-0.99) and the ratio of living-donors to all donors (living and deceased) (OR = 0.94, 95% CI = 0.92-0.96) were associated with a lower risk of all complications. Donor age >50 years (OR = 4.25, 95% CI = 1.22-14.87) was associated with a higher risk of major complications. Living liver donation is currently performed with a low risk of major morbidity. Use of administrative data represents an important tool to facilitate a better understanding of donor risk factors.

A donor right hepatectomy (RH) is associated with a higher rate of morbidity than a left hepatectomy. Therefore, the precise morbidity should be known to improve the success of donor RH implementation. However, the rate of complication varies according to the individual definition of morbidity. This study prospectively analyzed the outcomes of 83 consecutive living donor RHs between January 2002 and July 2004 using a standardized classification of the severity of complications. The morbidity was classified using the modified Clavien system: grade I for minor complications; grade II for potentially life-threatening complications requiring pharmacological treatment; grade III for complications requiring invasive intervention; grade IV for complications causing organ dysfunction requiring intensive care unit management; and grade V complications resulting in the death of the patient. The donors were followed-up regularly for at least 12 months. No donor death or relaparotomy was noted. Overall, 65 out of 83 donors (78.3%) experienced postoperative complications: grades I, II, III, IV, and V complications in 64 (77.1%), 11 (13.3%), 1 (1.2%), 0, and 0 patients, respectively. The most common grade I complications were hyperbilirubinemia (n = 31) and pleural effusion (n = 31), and bile leakage in grade II (n = 7). The bilirubin and alanine aminotransferase levels were normal in 92.7% of donors at the 1-year follow-up. In conclusion, although most of these adverse events were minor and self-limited, 78% of right liver donors still experienced morbidity. Therefore, continuous standardized reporting of the donor morbidity as well as meticulous surgery and intensive care are essential for the success of donor RH implementation.

The growing gap between the number of patients awaiting liver transplantation and available organs has continued to be the primary issue facing the transplant community. To overcome the waiting list mortality, living donor liver transplantation has become an option, in which the greatest concern is the safety of the donor, especially in adult-to-adult living donor liver transplantation (A-A LDLT) using a right lobe liver graft.

We evaluated the safety of donors after right lobe liver donation for A-A LDLT performed in our center.

From January 2002 to March 2006, 26 patients underwent A-A LDLT using right lobe liver grafts in our center. Seven donors were men and 19 were women (range, 19-65 years; median age, 38 years). The right lobe liver grafts were obtained by transecting the liver on the right side of the middle hepatic vein without interrupting the vascular blood flow. The mean follow-up time for these donors was 9 months.

These donor residual liver volumes ranged from 30.5% to 60.3%. We did not experience any donor mortality. Two cases (7.69%) experienced major complications: intra-abdominal bleeding and portal vein thrombosis in one each and three (11.54%), minor ones: wound steatosis in two, and transient chyle leak in one. All donors were fully recovered and returned to their previous occupations.

A-A LDLT using a right lobe liver graft has become a standard option. The donation of right lobe liver for A-A LDLT was a relatively safe procedure in our center.

Living-related liver transplantation has become the treatment of choice for many liver diseases. We present our initial analysis of 53 cases of adult to adult living-related liver transplantation performed in a single institute in Italy.

From January 2002 to September 2006, we performed 53 adult to adult living-related liver transplantations. The donors (age 18-53) all had genetic or emotional relationships; they were all ABO identical or compatible. Recipients (ages 18-68) suffered from cirrhosis secondary to viral etiology (18), hepatocellular carcinoma with viral cirrhosis (24), cystic fibrosis (2), primary biliary cirrhosis (2), hepatocellular carcinoma with non-viral cirrhosis (2), alcoholic cirrhosis (1), ornithine transcarbamylase deficiency (OTC), (1) criptogenic cryptogenic cirrhosis, (1) primary sclerosing cholangitis, (1) biliary atresia and metastatic carcinoid (1). Donor liver resection resulted in 51 right hepatectomies and two left hepatectomies. Graft body weight ratio was always above 0.8%; graft implantation was performed with the piggy back technique and, in 43 cases, with the use of veno-venous bypass.

There was neither donor mortality nor need of blood transfusion. Actuarial recipient survival rate at 3 years was 82.66% and graft survival rate was 75.34%. Six patients underwent retransplantation: in four cases due to hepatic artery thrombosis, and in two, due to graft dysfunction. Three patients had one episode each of acute cellular rejection.

Adult to adult living-related liver transplantation represents a resource to be used in confronting organ shortage, and is a valuable option for decreasing mortality and drop out from the waiting list.

It has been 16 years since the first successful living-donor liver transplant was performed from a parent to a child. The overall recipient and graft survival, together with a low morbidity and mortality in donors, have resulted in the widespread acceptance of the procedure by both the transplant community and the public at large. Adult-to-adult living-donor liver transplantation has been evolving over the past decade. Despite living-donor transplant patients being better-risk candidates than those who receive a graft from a deceased donor, and well-established and experienced units achieving satisfactory results, overall recipient and graft survival recorder by registries can only be described as suboptimal. This, combined with the high morbidity and not-insignificant mortality amongst donors makes expansion of adult-to-adult liver transplantation hard to justify on a risk-benefit analysis.

To define the current standards of donor right hepatectomy, including the middle hepatic vein for adult-to-adult live donor liver transplantation.

Donor morbidity and mortality are inevitable given the ultra-major nature of the donor operation. Results from a matured center could define the true impact of this donor procedure most accurately.

From May 9, 1996 to April 13, 2005, 200 consecutive donors underwent donor right hepatectomy at the University of Hong Kong Medical Center. All right liver grafts except one included the middle hepatic vein. Donor characteristics, operation time, blood loss, hospital stay, laboratory results, and complications graded by Clavien's classification divided into four eras (each consecutive 50 cases) were compared.

Donor characteristics of the four eras were generally comparable. Operative outcomes improved progressively through the four eras. From era 1 to era 4, operation time decreased from 598 minutes (range, 378-932 minutes) to 391 minutes (range, 304-635 minutes). Blood loss also decreased from 500 mL (200-1600 mL) of era 1 to 251 mL (range, 95-595 mL) of era 4. Overall complication rate was 20.5% (41 of 200). Complications rates from eras 1 to 4 were 34%, 16%, 16%, and 16%, respectively. The most common complications were of grade I (24 of 41, 58.5%). A late donor death occurred in era 4 from the development of a duodenocaval fistula 10 weeks postoperation, giving a donor mortality of 0.5% (1 of 200).

This study validated the estimated morbidity and mortality of donor right hepatectomy of 20% and 0.5%, respectively. The data provide reference for counseling potential donors and setting the standards of donor right hepatectomy in the current era.

Although organ transplantation has matured into a proven therapy for end-stage organ failure, the many notable developments of the past 5 years speak to the multitude of remaining challenges. Two new procedures, islet transplantation and adult-to-adult living donor liver transplantation, have emerged to enlarge our therapeutic armamentarium for Type 1 diabetes mellitus and end-stage liver disease, respectively. In cardiac transplantation, the acceptance of ventricular assist devices as destination therapy is a notable event in light of critical shortage of deceased donor organs. Both liver and lung allocation policies have made a dramatic paradigm shift away from waiting time toward the survival benefit of transplantation. Finally, primary threats to post-transplant longevity have gained an increasing share of the spotlight. Recognition of the impact of renal insufficiency for all nonrenal transplant recipients, of recurrent hepatitis C virus for liver recipients, and of accelerated vasculopathy for cardiac have identified novel end points for clinical trials.

The selection of donors for living donor liver transplantation (LDLT) is one of the most important features in this kind of surgery. The aim of this study is to describe our initial experience in the donor evaluation process. From December 2001 to January 2005, 104 donors were evaluated for 70 recipients (65 potential donors were evaluated for 39 adult recipients, and 39 donors for 31 pediatric recipients). Only 30 donors were able to donate: 13 for the adult group, and 17 for the pediatric one. In general, the utilization rate of potential donors was 28.8% (30/104). For the adult patients, 65 potential donors were seen to perform 13 LDLT, which represents a utilization rate of potential donors of 20%. For the pediatric patients, this rate was 43.6%. The exclusion criteria were clinical in 22 cases (21%), anatomical in 13 cases (13%), psychosocial in nine cases (9%), and others in 12 (12%). Death of recipients led to exclusion 18 of donors (17%). Thirty-three percent of adults and 55% of pediatric recipients who had at least one potential donor to start the evaluation process were able to identify a living donor. In conclusion, the first limit for LDLT is the rigorous donor evaluation.

To explore the use of medical journals, lay media, registries, and transplant center websites to discuss living liver donor mortality.

To study the incidence of and circumstances relating to living liver donor death, medical journals and lay print media were searched to create a case summary of worldwide living liver donor deaths. The United Network for Organ Sharing (UNOS) and European Liver Transplant Registry (ELTR) were also queried for information regarding living liver donor deaths. Lastly, the Websites of United States transplant centers offering living liver donation were reviewed to identify whether or not death was stated as a donor risk.

Literature review revealed 14 living liver donor deaths. One of the five deaths occurring in the United States had been reported to UNOS. One of the 14 cases had been reported only in lay literature, and another only in the ELTR. In at least five cases, surgical complications were not the cause of donor death. Among the 62 transplant center Websites, only 12 centers (19%) specifically mentioned death as a donation risk. Eight of these 12 centers (67%) mentioned death in terms of percent mortality risk; however, risk rates spanned a 10-fold range from 0.2% to 2%.

Potential living liver donors are best served by accurate information about donor mortality. Access to such data is difficult and these individuals would benefit by a worldwide living liver donor registry and peer-reviewed publication of donor mortality.

Living donor liver transplantation (LDLT) was initially developed to provide suitable liver grafts for pediatric patients with end-stage liver disease. This innovation was remarkable for the prospective nature of its development and the public discussions that resolved the ethical dilemma of removing a portion of a liver from a healthy donor for the benefit of another person. Since its inception, this procedure has been uniformly adopted by most pediatric transplant centers, with excellent results. Unfortunately, liver grafts obtained from this procedure did not provide sufficient hepatocyte mass for use in adult recipients. An adult donor procedure was, therefore, developed to provide larger liver grafts, which were derived from the right lobe of the liver. Much of the driving force for adult-to-adult LDLT has been in countries that lack the health-care infrastructure for obtaining deceased donors or have cultural objections to deceased donor transplantation. In developed countries, the initial growth of adult-to-adult LDLT has been tempered by notable donor complications, including death, but it continues to have an important role in providing life-saving liver grafts for recipients who are unable to compete for deceased donor grafts in the current organ-allocation system.

To overcome the barrier of size match, right lobe graft has been widely used in living donor liver transplantation (LDLT). We assessed donor outcome, with a focus on remnant liver volume (RLV) after right hepatectomy based on the experiences of 2 LDLT centers, as a means of guiding the establishment of safe RLV limits for donor right hepatectomy. Between January 2002 and December 2003, a consecutive 146 liver donors who underwent right hepatectomy with at least 12 months of follow-up were enrolled in this study. Donors were grouped into 2 groups according to RLV: group 1 (n = 74), <35% (range, 26.9-34.9) and group 2 (n = 72), > or = 35% (35.0-46.8). No donors died or suffered a life-threatening complication. Mean peak serum postoperative aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (IU/L) levels were 219.5 +/- 79.9 and 231.5 +/- 83.3 in group 1 and 210.3 +/- 81.6 and 225.8 +/- 93.0 in group 2 (P = 0.497 and 0.699), respectively. Mean peak serum total bilirubin (TB) (mg/dL) level in group 1 (3.4 +/- 1.6) was higher than in group 2 (2.8 +/- 1.4; P = 0.023). Overall 23 (15.8%) major morbidities, 10 in group 1 (13.5%) and 13 in group 2 (18.1%), occurred according to Clavien's system (P = 0.939). These included bleeding (n = 3 in group 1 and n = 6 in group 2; P = 0.282), ileus (n = 3 and 1; P = 0.324), biliary leakage (n = 4 and 4; P = 0.968), and pneumonia (n = 0 and 2; P = 0.149). Minor morbidities were also comparable in the 2 groups. In conclusion, the outcome of donors with an RLV of <35% was not different from that of donors with an RLV of > or = 35%, with the exception of transient cholestasis. Therefore, a remnant RLV of <35% does not appear to be a contraindication for right liver procurement in living donors.

The introduction of living donor liver transplantation (LDLT) has been one of the most remarkable steps in the field of liver transplantation (LT). First introduced for children in 1989, its adoption for adults has followed only 10 years later. As the demand for LT continues to increase, LDLT provides life-saving therapy for many patients who would otherwise die awaiting a cadaveric organ. In recent years, LDLT has been shown to be a clinically safe addition to deceased donor liver transplantation (DDLT) and has been able to significantly extend the scarce donor pool. As long as the donor shortage continues to increase, LDLT will play an important role in the future of LT.

The objective of this study was to evaluate the effect of systematic utilization of extended donor criteria liver allografts (EDC), including living donor allografts (LDLT), on patient access to liver transplantation (LTX).

Utilization of liver allografts that do not meet traditional donor criteria (EDC) offer immediate expansion of the donor pool. EDC are typically allocated by transplant center rather than regional wait-list priority (RA). This single-institution series compares outcomes of EDC and RA allocation to determine the impact of EDC utilization on donor use and patient access to LTX.

The authors conducted a retrospective analysis of 99 EDC recipients (49 deceased donor, 50 LDLT) and 116 RA recipients from April 2001 through April 2004. Deceased-donor EDC included: age >65 years, donation after cardiac death, positive viral serology (hepatitis C, hepatitis B core antibody, human T-cell lymphotrophic), split-liver, hypernatremia, prior carcinoma, steatosis, and behavioral high-risk donors. Outcome variables included patient and graft survival, hospitalization, initial graft function, and complication categorized as: biliary, vascular, wound, and other.

EDC recipients were more frequently diagnosed with hepatitis C virus or hepatocellular carcinoma and had a lower model for end-stage liver disease (MELD) score at LTX (P < 0.01). Wait-time, technical complications, and hospitalization were comparable. Log-rank analysis of Kaplan-Meier survival estimates demonstrated no difference in patient or graft survival; however, deaths among deceased-donor EDC recipients were frequently the result of patient comorbidities, whereas LDLT and RA deaths resulted from graft failure (P < 0.01). EDC increased patient access to LTX by 77% and reduced pre-LTX mortality by over 50% compared with regional data (P < 0.01).

Systematic EDC utilization maximizes donor use, increases access to LTX, and significantly reduces wait-list mortality by providing satisfactory outcomes to select recipients.

The shortage of deceased organ donors has created a need for right lobe living donor liver transplantation (RLDLT) in adults. Concerns regarding donor safety, however, necessitate continuous assessment of donor acceptance criteria and documentation of donor morbidity. We report the outcomes of our first 101 donors who underwent right lobectomy between April 2000 and November 2004. The cohort comprised 58 men and 43 women with a median age of 37.8 years (range: 18.6-55 years); median follow-up is 24 months. The middle hepatic vein (MHV) was taken with the graft in 55 donors. All complications were recorded prospectively and stratified by grade according to Clavien's classification. Overall morbidity rate was 37%; all complications were either grade 1 or 2, and the majority occurred during the first 30 days after surgery. Removal of the MHV did not affect morbidity rate. There were significantly fewer complications in the later half of our experience. All donors are well and have returned to full activities. With careful donor selection and specialized patient care, low morbidity rates can be achieved after right hepatectomy for living donor liver transplantation.

The objective of this study was to characterize the patient population with respect to patient selection, assess surgical morbidity and graft failures, and analyze the contribution of perioperative clinical factors to recipient outcome in adult living donor liver transplantation (ALDLT).

Previous reports have been center-specific or from large databases lacking detailed variables. The Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) represents the first detailed North American multicenter report of recipient risk and outcome aiming to characterize variables predictive of graft failure.

Three hundred eighty-five ALDLT recipients transplanted at 9 centers were studied with analysis of over 35 donor, recipient, intraoperative, and postoperative variables. Cox regression models were used to examine the relationship of variables to the risk of graft failure.

Ninety-day and 1-year graft survival were 87% and 81%, respectively. Fifty-one (13.2%) grafts failed in the first 90 days. The most common causes of graft failure were vascular thrombosis, primary nonfunction, and sepsis. Biliary complications were common (30% early, 11% late). Older recipient age and length of cold ischemia were significant predictors of graft failure. Center experience greater than 20 ALDLT was associated with a significantly lower risk of graft failure. Recipient Model for End-stage Liver Disease score and graft size were not significant predictors.

This multicenter A2ALL experience provides evidence that ALDLT is a viable option for liver replacement. Older recipient age and prolonged cold ischemia time increase the risk of graft failure. Outcomes improve with increasing center experience.

Liver transplant is the primary therapy for patients with end-stage liver disease. Its high success rates have lead to a broadening of the indications for liver transplantation, resulting in an increasing shortage of donors. Living donor liver transplantation has become an option to overcome waiting list mortality. We describe our experience with hepatectomy for living donor liver transplantation and report a case of death.

Patients (n = 132) underwent hepatectomy for living donor liver transplantation from June 2000 through June 2004. A 4-phase preoperative evaluation was performed on all patients, whose ages ranged from 13 to 54 years (mean = 29.7 +/- 8.1 years). Of the 132 patients, 76 patients (57.5%) underwent left lateral segmentectomy, 33 patients (25%) underwent left lobectomy, and 23 patients (16%) underwent right hepatectomy. In 2 other patients (1.5%), a monosegment (segment II) was obtained after left lateral segmentectomy.

Twenty patients (15%) experienced a complication, the most common being incisional hernia, pneumonia, and biliary fistulae. On the seventh postoperative day, 1 patient developed a fatal cerebral hemorrhage while recovering from mild liver dysfunction.

Although living donor liver transplantation is generally safe, serious and fatal complications may occur.

Organ transplantation occupies the center stage in the treatment of many forms of end-stage organ disease. When the limits of conventional medical care are exhausted, bridging therapies, cadaveric transplantation, and posttransplant medical care come to the fore. Living donor transplantation has grown out of the numerical and immunosuppression limitations of this process. Living donor transplantation medicine and surgery encompass two of the most fascinating and compelling social and ethical dilemmas of modern health care. This article provides an overview of medical and ethical concerns for those who decide to become living donors and those who care for them in the perioperative period.

A 57-year-old male with a history of hypercholesterolemia and anxiety but otherwise in good health volunteered to donate the right lobe of his liver to his brother. The operation was performed uneventfully, without transfusion. Postoperatively he did well, until he developed tachycardia, profound hypotension, and coffee ground emesis on postoperative day 3. Despite resuscitative measures, he arrested and expired. Autopsy demonstrated gas gangrene of the stomach as the underlying cause of the hemorrhage and numerous colonies of Gram-positive bacilli were identified. Subsequent polymerase chain reaction (PCR) analysis identified these bacteria to be Clostridium perfringens (C. perfringens) type D. This patient's death was devastating, both to his family and his medical team. The impact of his death has transcended that of an individual occurrence. In conclusion, herein we present the facts and discuss this extraordinary example of florid clostridial infection and toxin-mediated shock. It was completely unexpected and probably unpreventable, and its cause was almost inconceivable.