Standardized upfront Glissonean approach and liver hanging maneuver reduces bile leakage from the hepatic hilum in living donors.

Biliary complications after hepatectomy in living donors have yet to be eradicated. We hypothesized that a standardized upfront Glissonean approach and liver hanging maneuver (GH) would prevent mechanical and thermal injuries to the hilar plate of the remnant liver by determining the point of bile duct division and the final destination of hepatectomy preceding liver parenchymal transection (safety) and facilitate liver transection deep within the parenchyma and allow maximum length of hilar structures (rationality). GH was implemented in 2016 and its incidence of bile leakage was retrospectively compared against the conventional technique. GH comprises six steps: (1) development of the retrohepatic avascular plane between the right hepatic vein (RHV) and the middle hepatic vein (MHV) and isolation of the hepatic vein(s); (2) isolation of the right or left Glissonean pedicle with the corresponding Glissonean pedicles of the caudate lobe; (3) for right liver grafts and left liver grafts with the caudate lobe, passage of the tape for the liver hanging maneuver along the retrohepatic avascular plane and above the hilar plate, and for left liver grafts without the caudate lobe and for left lateral section grafts, passage of the tape from between the RHV and the MHV, along the Arantius ligament, and to the right of the umbilical portion; (4) liver transection; (5) isolation of hilar structures; and (6) graft procurement. Until 2020, 62 consecutive living donors underwent GH (success rate, 100%). The incidence of bile leakage from the hepatic hilum (0%) was significantly lower than that among 59 donors who underwent the conventional technique in 2011-2015 (9%; p = 0.01). In conclusion, GH is highly effective in reducing bile leakage from the hepatic hilum in living donors.

Hepatic venous outflow obstruction after adult living donor liver transplantation.

Hepatic venous outflow obstruction (HVOO) is a rare but critical vascular complication after adult living donor liver transplantation. We categorized HVOOs according to their morphology (anastomotic stenosis, kinking, and intrahepatic stenosis) and onset (early-onset < 3 mo vs. late-onset ≥ 3 mo). Overall, 16/324 (4.9%) patients developed HVOO between 2000 and 2020. Fifteen patients underwent interventional radiology. Of the 16 hepatic venous anastomoses within these 15 patients, 12 were anastomotic stenosis, 2 were kinking, and 2 were intrahepatic stenoses. All of the kinking and intrahepatic stenoses required stent placement, but most of the anastomotic stenoses (11/12, 92%) were successfully managed with balloon angioplasty, which avoided stent placement. Graft survival tended to be worse for patients with late-onset HVOO than early-onset HVOO (40% vs. 69.3% at 5 y, p = 0.162) despite successful interventional radiology. In conclusion, repeat balloon angioplasty can be considered for simple anastomotic stenosis, but stent placement is recommended for kinking or intrahepatic stenosis. Close follow-up is recommended in patients with late-onset HVOO even after successful treatment.

Short-term Outcomes of "Difficult" Laparoscopic Liver Resection at Specialized Centers: Report From INSTALL (International Survey on Technical Aspects of Laparoscopic Liver Resection)-2 on 4478 Patients.

OBJECTIVE: To define the current status of "difficult" LLR, a global database was created and investigated. BACKGROUND: In the Second International Consensus Conference in 2014, minor LLR was considered as a standard practice and major LLR remained an innovative procedure. Since then, no updates on worldwide trends have been available. METHODS: A questionnaire on all consecutive patients who underwent difficult LLR (major hepatectomy, posterosuperior segmentectomy, sectionec-tomy, living donor hepatectomy, tumor size ≥10 cm, Child-Pugh grade ≥B, combined with biliary reconstruction, and Iwate criteria difficulty score ≥7) in 2014-2018 was distributed via email to 65 high-volume LLR centers worldwide. individual data on patient and tumor demographics, surgical information, and short-term outcomes were obtained to create a large-scale international registry for analyses. RESULTS: Overall, 58 centers in 19 countries performed 4478 difficult LLR (median, 58.5; range, 5-418) during the study period. Hepatocellular carcinoma accounted for ≥ 40% of all indications. Half of the patients underwent major hepatectomy, followed by sectionectomy, posterosuperior segmentectomy, and living donor hepatectomy. in the vast majority of procedures, Clavien-Dindo grade ≥IIIa complication rates of ≈10% and 90-day mortality rates of ≈1% were achieved. Left or right trisectionectomy had the worst Clavien-Dindo grade ≥IIIa complication rate of ≥10% and 90-day mortality rate of 5%-10%. No significant correlation was observed between center volume and short-term outcomes. CONCLUSIONS: Total 4478 patients underwent difficult LLR worldwide in 2014-2018. Most procedures are safe and feasible when conducted in specialized centers.

Portal Vein Complications After Adult Living Donor Liver Transplantation: Time of Onset and Deformity Patterns Affect Long-Term Outcomes.

Portal vein complications (PVCs) after adult living donor liver transplantation (LDLT) are potentially lethal. We categorized PVCs by the time of onset (early versus late, <1 month versus ≥1 month, respectively) and deformity patterns (portal vein stenosis [PVS], portal vein thrombosis [PVT], and portal vein occlusion [PVO]) to establish optimal treatment strategies. Overall, 35/322 (10.9%) recipients developed PVCs between 2000 and 2019. Pretransplant PVT (odds ratio [OR], 15.20; 95% confidence interval [CI], 3.70-62.40; P < 0.001) was the only independent risk factor for PVS. In contrast, male sex (OR, 5.57; 95% CI, 1.71-18.20; P = 0.004), pretransplant PVT (OR, 4.79; 95% CI, 1.64-14.00; P = 0.004), and splenectomy (OR, 3.24; 95% CI, 1.23-8.57; P = 0.018) were independent risk factors for PVT. PVS was successfully treated with interventional radiology regardless of its time of onset. On the other hand, late PVT and PVO had significantly lower treatment success rates (2/15, 13%) compared with those that occurred in the early period (10/11, 91%) despite aggressive intervention (P < 0.001). Deformity patterns had a significant impact on the 5-year cumulative incidence of graft loss as a result of PVC (PVO + Yerdel grades 2-4 PVT group [n = 16], 41% versus PVS + Yerdel grade 1 PVT group [n = 19], 0%; P = 0.02). In conclusion, late grades 2 to 4 PVT and PVO are refractory to treatment and associated with poor prognoses, whereas PVS has a good prognosis regardless of time of onset. A tailored approach according to the time of onset and deformity patterns of PVC is essential.

Asymptomatic hepatic artery dissection early after living-donor liver transplantation with simultaneous splenectomy: two case reports.

BACKGROUND: Hepatic artery dissection after liver transplantation is an uncommon morbidity. The onset mechanism and management for this disorder remain unclear. The present report describes the cases of two patients with hepatic artery dissection after living-donor liver transplantation (LDLT) with simultaneous splenectomy and provides new insight into the onset mechanism of this disorder. CASE PRESENTATION: CASE 1: A 51-year-old man with liver cirrhosis caused by hepatitis B virus underwent LDLT with a right lobe graft and splenectomy simultaneously. The recipient's right hepatic artery had partial dissection at the anastomosis site; therefore, his left hepatic artery was anastomosed. Contrast-enhanced computed tomography (CT) on postoperative day (POD) 27 showed dissection from his celiac artery to his left hepatic artery with bleeding in the false lumen. There was a risk of rupture of the false lumen; therefore, emergency interventional radiology and coil embolization of the false lumen were performed. The patient was doing well at 6 months after LDLT. CASE 2: A 58-year-old woman with liver cirrhosis caused by primary biliary cholangitis underwent LDLT with a left lobe graft and splenectomy simultaneously. Her hepatic artery had a dissection that extended from her left hepatic artery to the proper hepatic artery. The gastroduodenal artery was anastomosed. Contrast-enhanced CT on POD 8 revealed dissection from the celiac artery to the common hepatic artery as well as a pseudoaneurysm at the celiac artery. We managed the patient with conservative treatment and performed daily follow-ups with Doppler ultrasonography examination and serial contrast-enhanced CT. At the time of writing this report, the patient was doing well at 34 months after LDLT. CONCLUSIONS: Patients who have an intimal dissection at the anastomosis site and/or simultaneous splenectomy are at a higher risk of hepatic artery dissection. Most patients with asymptomatic hepatic artery dissections can be treated conservatively. Blood flow in the intrahepatic artery should be checked frequently using Doppler ultrasonography or contrast-enhanced CT soon after diagnosis.

[A Case Report of Successful Treatment with Dose-controlled mFOFOX6+Bevacizumab for Metastatic Colorectal Cancer in Patient Receiving Hemodialysis].

A 65-years-old man undergoing hemodialysis for chronic kidney disease was diagnosed with ascending colon cancer and 3 hepatic metastases. He was administered mFOLFOX6 (reducing the dose to 50%) plus bevacizumab (BEV) therapy. Hemodialysis was performed 4 h after administration of oxaliplatin on day1 and repeated three times a week. No serious adverse events were observed. After 4 courses of chemotherapy, a computer tomography scan showed that the hepatic metastases had reduced. 2 courses of mFOLFOX6 (increasing the dose to 75%) plus BEV therapy were added, he was operated by laparoscopic right hemicolectomy and laparoscopic patrial hepatectomy. He has been in remission for 2 years and 4 months since the surgery. Dose-adjusted chemotherapy with hemodialysis was effective and improve the prognosis of the patient.

Elevated Alfa-Fetoprotein and Des-Gamma-Carboxy Prothrombin Levels Predict Poor Outcomes After Liver Transplantation for Hepatocellular Carcinoma Beyond the Japan Criteria.

AIM: The Japan criteria (Milan criteria + 5-5-500 rule) was established recently to select cirrhotic patients with hepatocellular carcinoma for liver transplantation. We evaluated factors associated with poor prognosis after liver transplantation and investigated whether a further extension of the criteria would be worthwhile. METHODS: We retrospectively analyzed 86 patients who underwent liver transplantation for hepatocellular carcinoma at Kumamoto University Hospital since 2004; 69 patients (80.2%) met the Japan criteria (the JCIN group), and 17 patients (19.8%) did not (the JCOUT group). RESULTS: The 5-year cancer-specific survival rates of the JCIN group (92.2%) were significantly better than that of the JCOUT group (39.2%; P < .001). In univariable analysis, alfa-fetoprotein and des-gamma-carboxy prothrombin were significant independent factors associated with cancer-specific survival rates. According to the receiver operating characteristic curves, the cutoff values of alfa-fetoprotein and des-gamma-carboxy prothrombin that predicted hepatocellular carcinoma recurrence after liver transplantation were 756 ng/mL and 1976 mAU/mL, respectively. The JCOUT group was divided into 2 subgroups according to alfa-fetoprotein and des-gamma-carboxy prothrombin: low risk (alfa-fetoprotein level <756 ng/mL and des-gamma-carboxy prothrombin level <1976 mAU/mL) and high risk (alfa-fetoprotein level ≥756 ng/mL and/or des-gamma-carboxy prothrombin level ≥1976 mAU/mL). The 5-year cancer-specific survival rate in the low-risk group (67.5%) was significantly better than that in the high-risk group (0%; P < .001). CONCLUSIONS: Alfa-fetoprotein levels of <756 ng/mL and des-gamma-carboxy prothrombin levels of <1976 mAU/mL may help identify cirrhotic patients with hepatocellular carcinoma who do not meet the Japan criteria but still benefit from liver transplantation.

Hungry Bone Syndrome After Living Donor Liver Transplant for Biliary Atresia.

Hungry bone syndrome is a rare but potentially lethal complication that is characterized by rapid, severe, long-lasting hypocalcemia and hypophosphatemia secondary to increased bone metabolism. We present a case of hungry bone syndrome after living donor liver transplant for biliary atresia. Following a failed Kasai procedure for biliary atresia, a 5-month-old boy underwent living donor liver transplant with reduced left lateral lobe from his father. Despite the oral administration of alfacalcidol, the patient exhibited severe craniotabes before the surgery. He developed severe hypocalcemia and hypophosphatemia im-mediately after liver transplant and required supplementation of calcium and phosphorus for 1 month thereafter. After serum levels of calcium and phosphate had normalized, there was a rapid increase in the serum bone-type alkaline phosphatase level, and the craniotabes subsided remarkably. To our knowledge, this is the world's first reported case of hungry bone syndrome after liver transplant for cholestatic cirrhosis. It underscores the importance of strict nutritional and electrolyte management in the perioperative period. A prompt diagnosis and correction of hungry bone syndrome are imperative to prevent the associated significant morbidity and mortality.

Long-term outcomes of living donor liver transplantation in patients with a prior history of nonhepatic malignancy.

Posttransplant malignancy has become a significant cause of mortality. Data on the long-term outcomes of patients with pretransplant nonhepatic malignancy (PTM) after living donor liver transplantation (LDLT) are scarce, although the recipients of other organs with PTM have been reported to have a poor survival. Fifteen patients with PTM (4.4%) among the 342 adult recipients were identified in our LDLT programs. The outcomes of the patients with PTM after LDLT were compared to those of patients without PTM in terms of the all-cause mortality and cancer-specific mortality (defined as mortality related to malignancy expect for hepatocellular carcinoma, cholangiocarcinoma, or neuroendocrine tumor). The sites of PTM included the breast in six, stomach in two, and colon, lung, kidney, uterine, thyroid, larynx, and acute myelogenous leukemia in one each. The median interval from the PTM treatment to LDLT was 57 months (range, 2-298). The patients who received the curative treatment for PTM were selected as the recipients. No patients with PTM had recurrence during the follow-up period. The 1-, 5-, and 10-year patient survival rates were 100%, 92.9%, and 92.9% in the PTM group and 86.2%, 76.7%, and 68.5% in the non-PTM group, respectively (p = 0.142). Likewise, there was no significant difference between the two groups in the cancer-specific mortality. In conclusion, the patients with PTM had comparable outcomes with regard to mortality and cancer-specific mortality compared with those without PTM. This study showed that the patients with PTM can obtain an acceptable outcome after LDLT when carefully selected.

Two-staged biliary reconstruction with temporary complete external biliary drainage as a bailout procedure in a pediatric patient after difficult living donor liver retransplantation.

Biliary leakage at the site of the hepaticojejunostomy after liver transplantation is a life-threatening complication. We herein present the case of a 7-year-old girl who underwent complete external biliary drainage during difficult living donor liver retransplantation as a bailout procedure. The patient had undergone duct-to-duct biliary reconstruction in the initial living donor liver transplantation. In the retransplantation, Roux-en-Y (RY) reconstruction was planned but abandoned due to the critical condition in the operation. As an alternative procedure, the patient underwent complete external drainage using a 6Fr drainage tube with cuff. Five months after retransplantation when the nutrition status and physical strength of a patient recovered fully, RY hepaticojejunostomy was successfully performed. This is a case report of two-staged biliary reconstruction with temporary complete external biliary drainage used in pediatric liver retransplantation, which was performed after some months not a few days. It is a safe and feasible alternative when primary anastomosis is deemed to carry a high risk of bile leakage in cases of difficult liver transplantation in critically ill patients.

Living donor liver transplantation for a patient with a history of total gastrectomy.

Adhesions due to previous upper abdominal surgery may complicate later liver transplantation. Here we report successful living donor liver transplantation (LDLT) in a patient with a history of total gastrectomy. A 32-year-old Japanese woman developed end-stage liver failure due to alcoholic cirrhosis. She had undergone total gastrectomy, pancreato-splenectomy, and partial colectomy due to rupture of a pancreatic cyst. LDLT was performed using a right lobe graft from her sister. To minimize blood loss and injury to the jejunum, adhesions between the left lobe and nearby organs were dissected without blood flow in or out of the liver. The right liver graft was implanted uneventfully. She was extubated on postoperative day (POD) 1, but then developed septic shock due to aspiration pneumonia on POD 2. She was reintubated and antibiotics and antifungal agents were administered. Administration of tacrolimus was changed to an intravenous route on POD 3. Her condition improved and she was re-extubated on POD 9. On POD 14, tacrolimus was administered orally. She was discharged from our hospital on POD 30 without any other events and is doing well 6 months after LDLT. We believe that careful planning, such as mobilizing the left lobe with the blood flow blocked just before liver explantation, elevating the head of the bed during tube-feeding, and calculating the area under the curve after drug administration will enable liver transplantation for patients with a history of total gastrectomy.

Colon perforation due to antigenemia-negative cytomegalovirus gastroenteritis after liver transplantation: A case report and review of literature.

BACKGROUND: Cytomegalovirus (CMV) remains a critical complication after solid-organ transplantation. The CMV antigenemia (AG) test is useful for monitoring CMV infection. Although the AG-positivity rate in CMV gastroenteritis is known to be low at onset, almost all cases become positive during the disease course. We treated a patient with transverse colon perforation due to AG-negative CMV gastroenteritis, following a living donor liver transplantation (LDLT). CASE SUMMARY: The patient was a 52-year-old woman with decompensated liver cirrhosis as a result of autoimmune hepatitis who underwent a blood-type compatible LDLT with her second son as the donor. On day 20 after surgery, upper and lower gastrointestinal endoscopy (GE) revealed multiple gastric ulcers and transverse colon ulcers. The biopsy tissue immunostaining confirmed a diagnosis of CMV gastroenteritis. On day 28 after surgery, an abdominal computed tomography revealed transverse colon perforation, and simple lavage and drainage were performed along with an urgent ileostomy. Although the repeated remission and aggravation of CMV gastroenteritis and acute cellular rejection made the control of immunosuppression difficult, the upper GE eventually revealed an improvement in the gastric ulcers, and the biopsy samples were negative for CMV. The CMV-AG test remained negative, therefore, we had to evaluate the status of the CMV infection on the basis of the clinical symptoms and GE. CONCLUSION: This case report suggests a monitoring method that could be useful for AG-negative CMV gastroenteritis after a solid-organ transplantation.

A Case Report of Hepatocellular Carcinoma in a Non-cirrhotic Patient With Liver Iron Overload Associated With Myelodysplastic Syndrome.

Hereditary hemochromatosis (HH) is associated with an increased risk for hepatocellular carcinoma (HCC) occurring predominantly in patients with cirrhosis at the time of diagnosis. However, HCC in non-cirrhotic liver of patients with secondary hemochromatosis is rare. A 67-year-old man with a history of myelodysplastic syndrome (MDS) was found to have a liver tumor on abdominal computed tomography (CT). On the basis of findings of high levels of serum ferritin and transferrin saturation, and low intensity of liver parenchyma on magnetic resonance imaging (MRI), we made a diagnosis of hemochromatosis. Liver resection was performed and the specimen showed moderately differentiated hepatocellular carcinoma surrounded by non-cirrhotic liver parenchyma with intracellular iron deposition. Multicentric recurrence of liver tumor occurred 2 years after the surgery despite of deferoxamine therapy with well controlled ferritin level. We reported a case of hepatocellular carcinoma in a non-cirrhotic patient with liver iron overload secondary to MDS. It demonstrated the importance of early detection and initiation of treatment of iron overload in preventing HCC in MDS patients, even among Asian population.