DCLK1 Expression and its Functional Significance in Intrahepatic Cholangiocarcinoma and Bil-IN Stage.

BACKGROUND/AIM: Although several studies in some neoplasms have reported correlation between the expression levels of Doublecortin-like kinase1(DCLK1) and carcinogenesis, its role in cholangiocarcinoma remains unknown. MATERIALS AND METHODS: DCLK1 expression in normal epithelium (NE), biliary intraepithelial neoplasia (BilIN)1∼3, and intrahepatic cholangiocarcinoma (ICC) were investigated immuno-histochemically. The molecular effects of DCLK1 were investigated by gene silencing using RNAi [DCLK1-tagrgeting (siDCLK1)]. The human ICC cell lines HuCCT1 and HuH28 were transfected with these siRNAs, and used for assays in the presence or absence of DCLK1 inhibitors. RESULTS: The positive ratio of DCLK1 expression in ICC was higher than that in NE, and equally distributed among BilIN1∼3 (NE: BilIN1: BilIN2: BilIN3: ICC=62%: 91%: 97%: 100%: 95%, p<0.05). In the wound healing assay, the migration of the siDCLK1-treated cells was significantly inhibited compared to the NT-treated cells (p<0.05). In the cell invasion assay, the invasion of the siDCLK1-treated cells was significantly inhibited compared to the NT-treated cells (p<0.05). In the presence of the DCLK1 inhibitor, cell proliferative capacity at 24 hours was decreased in a concentration-dependent manner. CONCLUSION: DCLK1 was highly expressed in the early stage of ICC carcinogenesis. Human ICC cell growth was suppressed in vitro by siRNA silencing of DCLK1 or after treatment with the DCLK1 inhibitor, indicating DCLK1 may be molecular target for ICC therapy.

Analysis of the Clinical Course in a Population of Patients with Biliary Tract Cancer Diagnosed as Unresectable After Portal Vein Embolization: A Case Series.

Portal vein embolization (PVE) is recommended as a preoperative procedure for patients with biliary tract cancer scheduled to undergo hepatic resection of more than 50%-60% of the liver. However, details and/or information regarding the follow-up of unresectable cases are often lacking, and the clinical course of unresectable cases is not well analyzed and reported. This study aimed to clarify the clinical prognosis of patients with unresectable biliary tract cancer after PVE. We retrospectively analyzed the clinical backgrounds of patients with biliary tract cancer who underwent PVE without subsequent resection between January 2011 and October 2022. Of the 21 patients with biliary tract cancer who underwent PVE during the study period, eight (38%) cases were unsuitable for resection after PVE for the following reasons: intraoperatively detected dissemination (n=2), para-aortic lymph node metastasis (n=1), liver metastasis (n=1), decreased liver function (n=2), development of liver metastasis while waiting (n=1), and insufficient residual liver volume (n=1). All patients received subsequent chemotherapy, including gemcitabine plus S-1 therapy in three cases, gemcitabine plus cisplatin plus S-1 in three cases, and gemcitabine plus cisplatin or S-1+cisplatin in one case each. As there is currently no curative treatment for biliary tract cancer other than surgery, multidisciplinary management and treatment of patient factors, including tumor factors and liver function, are essential to reducing the number of unresectable cases after PVE.

[Air embolism after biliary stent removal during endoscopic retrograde cholangiopancreatography for cholangitis after biliary reconstruction: a case report].

A 62-year-old male patient underwent pancreaticoduodenectomy with modified Child reconstruction for distal cholangiocarcinoma. After eight years, a contrast-enhanced computed tomography (CT) revealed a recurrent lesion at the biliojejunal anastomosis, and a biliary stent was placed for obstructive cholangitis in the right posterior segment of the liver. A right hepatectomy was planned for a local recurrent lesion;thus, percutaneous transhepatic portal embolization was performed on the portal vein's right branch to enlarge the left liver. However, he was referred to our department for endoscopic retrograde biliary drainage for the subsequent cholangitis and liver abscess appearance. A double-balloon enteroscope under CO2 insufflation was used to reach the bile duct-jejunal anastomosis. After removing the bile duct stent with grasping forceps, his general condition suddenly deteriorated, causing cardiopulmonary arrest. He was diagnosed with air embolism based on the findings of air in the heart, aorta, and brain on CT after the return of spontaneous circulation. Treatment for the air embolism and subsequent complications continued in the intensive care unit, but he eventually died 114 days after the onset of the air embolism due to his deteriorating general condition. Pathological autopsy revealed cholangiocarcinoma that extends from the porta hepatis to the posterior segment. Additionally, the proximity between the bile duct and vein extended by the adenocarcinoma and the fibrous obstruction of the vein were revealed, indicating the possibility of a bile duct-vein shunt.

An Analysis of 10,000 Cases of Living Donor Liver Transplantation in Japan: Special Reference to the Graft-Versus-Recipient Weight Ratio and Donor Age.

OBJECTIVE: To analyze 10,000 cases of living donor liver transplantation (LDLT) recipient data to elucidate outcomes with special reference to the graft-versus-recipient weight ratio (GRWR), based on the Japanese Liver Transplantation Society (JLTS) registry. BACKGROUND: The JLTS registry has been accurate and complete in characterizing and following trends in patient characteristics and survival of all patients with LDLT. METHODS: Between November 1989 and August 2021, 10,000 patients underwent LDLT in Japan. The procedures performed during the study period included pediatric liver transplantation (age <18 years, n = 3572) and adult liver transplantation (age ≥18 years, n=6428). Factors related to patient survival (PS) and graft survival (GS) were also analyzed. RESULTS: The GRWR was <0.7, 0.7 to <0.8, 0.8 to <3, 3 to <5, and ≥5 in 0.2%, 2.0%, 61.8%, 31.8%, and 2.6% of pediatric patients and <0.6, 0.6 to <0.7, 0.7 to <0.8, and ≥0.8 in 8.0%, 12.7%, 17.7%, and 61.5% of adult patients, respectively. Among pediatric recipients, the PS rate up to 5 years was significantly better in cases with a GRWR ≤5 than in those with a GRWR >5. When the GRWR and donor age were combined, among adult recipients 50 to 60 years old, the early PS and GS up to 5 years were significantly better in cases with a GRWR ≥0.7, than in those with a GRWR <0.7. (P = 0.02). In adults, a multivariate analysis showed that GRWR <0.6, transplant era (<2011), donor age (>60 years), recipient age (>60 years), model for end-stage liver disease score (≥20), and center volume (<10) were significant prognostic factors for long-term PS. CONCLUSION: Although a satisfactory long-term PS and GS, especially in the recent era (2011-2021), was achieved in the JLTS series, a GRWR ≥5 in pediatric cases and relatively old donors with a GRWR <0.7 in adult cases should be managed with caution.

Serum wisteria floribunda agglutinin-positive human Mac-2 binding protein is unsuitable as a diagnostic marker of occult hepatocellular carcinoma in end-stage liver cirrhosis.

BACKGROUND AND PURPOSE: Serum glycosylated Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+-M2BP) is a marker of liver fibrosis and hepatocellular carcinoma (HCC). In this study, we aimed to evaluate the diagnostic ability of WFA+-M2BP for occult HCC, which current diagnostic imaging tests fail to detect. METHODS: Patients who underwent hepatectomy for liver transplantation (LT) and whose whole liver could be sliced and subjected to histological examination between 2010 and 2018 were eligible for this study (n = 89). WFA+-M2BP levels were measured in samples collected before the LT. Comparison of the postoperative histological test results with the preoperative imaging data grouped the patients into histologically no group (N), histologically detected group (D), histologically increased group (I), and histologically decreased or same group (DS), and the results were compared with the WFA+-M2BP values. In addition, comparisons were made between each data with and without HCC, including occult HCC, and total tumor diameter. RESULTS: Irrespective of underlying hepatic disease conditions, there were 6 patients in the N group, 10 in the D group, 41 in the I group, and 32 in the DS group. The median of the serum WFA+-M2BP level for each group was as follows: N group, 8.05 (1.25-11.9); D group, 11.025 (1.01-18.21); I group, 9.67 (0.29-17.83); and DS group, 9.56 (0.28-19.44) confidence of interval. We found no significant differences between the pairings. Comparison of underlying hepatic diseases revealed that liver cirrhosis due to hepatitis B and C and non-B and -C liver cirrhosis had no significant differences. AFP levels, on the other hand, had significant relationships in comparison between the presence or absence of histological HCC, in correlation between total tumor diameter, and in the ROC analysis for the diagnosis of HCC including occult HCC. CONCLUSION: Serum WFA+-M2BP cannot help diagnose occult HCC that is already undetected using imaging tests in decompensated liver cirrhosis patients requiring LT.

Living donor liver transplantation for a patient with acute liver failure following thyroid storm: a case report.

BACKGROUND: Thyroid storm can be complicated by liver dysfunction, which may occasionally progress to acute liver failure. We herein report a case of acute liver failure following thyroid storm that was treated with living donor liver transplantation after resuscitation from cardiopulmonary arrest. CASE REPORT: The patient was a woman in her 40 s who had been diagnosed with an abnormal thyroid function. She suffered from fatigue and vomiting, and was found to have consciousness disorder, a fever, and tachycardia with a neck mass. She was diagnosed with thyroid storm and was referred to our hospital. After arrival, she went into cardiopulmonary arrest and veno-arterial extracorporeal membrane oxygenation was initiated. In addition to treatment for thyroid storm with antithyroid drugs, steroids, and plasma exchange, extracorporeal life support was required for 5 days. However, despite improvements in her thyroid function, her liver function deteriorated. We planned living donor liver transplantation for acute liver failure after ensuring the recovery and control of the thyroid function following total thyroidectomy. The donor was her husband who donated the right lobe of his liver. Although she experienced acute cellular rejection after surgery, and other complications-including intra-abdominal hemorrhaging and ischemic changes in the intestine-her liver function and general condition gradually improved. One year after living donor liver transplantation, the patient was in a good condition with a normal liver function. CONCLUSIONS: To our knowledge, this is the first report of living donor liver transplantation in a patient with acute liver failure following thyroid storm. Liver transplantation should be recognized as an effective treatment for acute liver failure following thyroid storm.

Pathologic Complete Response after Chemotherapy with Atezolizumab plus Bevacizumab for Hepatocellular Carcinoma with Tumor Thrombus in the Main Portal Trunk.

We report a case of pathologic complete response after successful treatment for advanced hepatocellular carcinoma (HCC) complicated with portal venous tumor thrombus with atezolizumab and bevacizumab followed by radical resection. The patient was a male in his 60s. During follow-up for chronic hepatitis B, abdominal ultrasonography revealed a huge tumor located in the right lobe of the liver with the portal vein thrombosed by the tumor. The tumor thrombus extended to the proximal side of the left branch of the portal vein. The patient's tumor marker levels were elevated (alpha-phetoprotein, 14,696 ng/mL; PIVKA-II, 2,141 mAU/mL). Liver biopsy revealed poorly differentiated HCC. The lesion was categorized as advanced stage according to the BCLC staging system. As systemic therapy, atezolizumab plus bevacizumab was administered. Imaging showed marked shrinkage of the tumor and portal venous thrombus with a remarkable decrease of tumor marker levels after 2 courses of chemotherapy. After 3 additional courses of chemotherapy, radical resection was considered possible. The patient underwent right hemihepatectomy and portal venous thrombectomy. A pathological examination revealed a complete response. In conclusion, we experienced a case in which advanced HCC was curatively treated with atezolizumab plus bevacizumab, which was administered as systemic therapy with a view to conversion surgery.

A hybrid procedure of living donor liver transplantation for a pediatric patient with citrin deficiency.

BACKGROUND: The application of laparoscopic procedures in the liver surgery has been growing. We herein present the first case of a pediatric patient who underwent living donor liver transplantation (LDLT) using a hybrid procedure with hand-assisted laparoscopic mobilization of the liver, subsequent explantation of the diseased liver, and implantation of the graft under direct vision. METHODS: A 12-year-old girl with citrin deficiency was scheduled for LDLT with a left lobe graft. After making an 8-cm upper midline incision, a 5-mm trocar was placed at the umbilicus and the right upper abdomen. Mobilization of the right liver lobe was performed using a hand-assisted laparoscopic surgery (HALS) procedure. After the extension of the midline incision, short hepatic vein dissection, encircling the right hepatic vein and hepatic hilum dissection was performed. Explantation of the liver and subsequent implantation of the liver graft were conducted under direct vision. RESULTS: Since the operation, her normal activities of daily life have been maintained with a normal liver function. Subsequently, her secondary sexual characteristics have recovered without any wound-related complications. CONCLUSIONS: A hybrid LDLT procedure was feasible for a pediatric patient. This procedure's benefits are considered meaningful for pediatric patients as it does not disrupt the rectus muscles or nerves and achieves cosmesis.

Stress exacerbates pancreatic cancer both directly and indirectly by creating an immunosuppressive environment.

BACKGROUND/PURPOSE: Sympathetic nerve stimulation by stress exacerbates various solid tumors, including pancreatic cancer (PCa). The relationship between cancer and immunity has been suggested; however, there is limited information about the effects of nerve stimulation on immunity and cancer. We aimed to investigate the involvement of sympathetic nerve stimulation in immune cells and its effects on PCa using a restraint stress mouse model. METHODS: In the in vitro experiment, the mouse-derived PCa cell line (LTPA) was cultured in a noradrenalin-supplemented medium. In the in vivo experiment, mice were divided into non-stress and stress groups. RESULTS: LTPA proliferated significantly more when cultured in a noradrenalin-supplemented medium than in a normal medium. Flow cytometry analysis of blood immune cells revealed a significant decrease in B cells, T cells, and macrophages and a significant increase in myeloid-derived suppressor cells (MDSCs) in the stress group. Furthermore, a significant increase in blood noradrenaline levels was observed in the stress group (p < .01). In the PCa mice model, immune cells in the blood showed a similar trend, and the stress group had a poor prognosis. Furthermore, immunostaining at the tumor site showed that there was a lower number of B and T cells in the stress group. In addition, MDSCs were present at the tumor margins. CONCLUSION: These results suggest that sympathetic nerve stimulation is not only directly involved in PCa growth but also exacerbates PCa by creating an immunosuppressive environment in the blood and tumor tissue.

Association between hospital acquired disability and post-discharge mortality in patients after living donor liver transplantation.

BACKGROUND: Hospital-acquired disability (HAD) in patients who undergo living donor liver transplantation (LDLT) is expected to worsen physical functions due to inactivity during hospitalization. The aim of this study was to explore whether a decline in activities of daily living from hospital admission to discharge is associated with prognosis in LDLT patients, who once discharged from a hospital. METHODS: We retrospectively examined the relationship between HAD and prognosis in 135 patients who underwent LDLT from June 2008 to June 2018, and discharged from hospital once. HAD was defined as a decline of over 5 points in the Barthel Index as an activity of daily living assessment. Additionally, LDLT patients were classified into four groups: low or high skeletal muscle index (SMI) and HAD or non-HAD. Univariate and multivariate Cox proportional hazard models were used to evaluate the association between HAD and survival. RESULTS: HAD was identified in 47 LDLT patients (34.8%). The HAD group had a significantly higher all-cause mortality than the non-HAD group (log-rank: p < 0.001), and in the HAD/low SMI group, all-cause mortality was highest between the groups (log-rank: p < 0.001). In multivariable analysis, HAD was an independent risk factor for all-cause mortality (hazard ratio [HR]: 16.54; P < 0.001) and HAD/low SMI group (HR: 16.82; P = 0.002). CONCLUSION: HAD was identified as an independent risk factor for all-cause mortality suggesting that it could be a key component in determining prognosis after LDLT. Future larger-scale studies are needed to consider the overall new strategy of perioperative rehabilitation, including enhancement of preoperative physiotherapy programs to improve physical function.

A Single-site Interventional Study on the Contemporary Relevance of Braun Enteroenterostomy After Pancreaticoduodenectomy.

BACKGROUND/AIM: Braun enteroenterostomy following pancreaticoduodenectomy is a standard procedure. It has been reported to decrease bile reflux and vomiting, prevent reflux gastritis and delay gastric emptying (DGE). However, some reports suggest that the incidence of DGE is unaffected with this procedure. Therefore, in this study, we aimed to investigate whether Braun enteroenterostomy was effective after pancreaticoduodenectomy. PATIENTS AND METHODS: A total of 145 patients who underwent pancreaticoduodenectomy were enrolled and divided into 2 groups i.e., 51 patients with Braun enteroenterostomy (B group) and 94 patients without Braun enteroenterostomy (non-B group). We compared the perioperative data of the patients. Patients who reported postoperative symptoms underwent gastrointestinal endoscopic evaluation. RESULTS: The incidence of DGE was 7.4% (7/94) and 1.9% (1/51) in the non-B and B groups, respectively (p=0.36), with no significant difference between the groups. During follow-up, some patients reported symptoms including epigastralgia, nausea and melena. The incidence of these symptoms was 27.7% (26 patients; 26/94) and 23.5% (12 patients; 12/51) in non-B and B groups, respectively. Regarding gastrointestinal endoscopic findings, the incidence of anastomotic ulcer was 7.7% (2/26) and 16.7% (2/12) in non-B and B groups, respectively (p=0.40). Bile reflux incidence was 30.8% (8/26) and 0% (0/12) in non-B and B groups, respectively (p=0.03). CONCLUSION: Though Braun enteroenterostomy was related to bile reflux, it did not affect the incidence of anastomotic and gastric ulcers or DGE. Therefore, it may not be a necessary procedure after pancreaticoduodenectomy.

Cytomegalovirus Graft Duodenitis Diagnosed by Transanal Double-Balloon Endoscopy Technique in an Enteric-Drained Pancreas Transplant Recipient: A Case Report.

Duodenal graft complications are not uncommon after pancreas transplant (PTx). Although direct visualization and biopsy of the duodenal graft are important for accurate diagnosis and management, endoscopic access is often limited in cases of enteric-drained PTx. Herein, we present a case of cytomegalovirus (CMV) graft duodenitis that was successfully diagnosed by transanal endoscopy using the double-balloon technique. The patient was a 54-year-old woman who underwent simultaneous pancreas and kidney transplant for type 1 diabetes mellitus and end-stage kidney disease. Enteric drainage was established by anastomosing the graft duodenum to her ileum. One month after the transplant, she developed fever and complained of lower abdominal pain. Graft duodenitis was suspected by laboratory test and imaging study results. Transanal double-balloon endoscopy was performed, and the biopsy specimen of the mucosa of the graft duodenum revealed CMV duodenitis without histopathologic findings of acute rejection. The postendoscopy course was uneventful. Treatment with ganciclovir was promptly initiated, and the CMV duodenitis was resolved with good function of the pancreas graft. In patients who undergo PTx with establishment of exocrine drainage by enteroanastomosis to the recipient ileum, transanal double-balloon endoscopy might be a feasible and safe technique for the surveillance of duodenal graft complications, including CMV duodenitis.

The Effects of Vonoprazan Fumarate on the Tacrolimus Blood Concentration in Liver Transplant Recipients.

BACKGROUND/AIM: The proton pump inhibitors were reported to affect the blood concentration of tacrolimus. Vonoprazan fumarate is a new acid suppressant with potent acid inhibitory effects. There have been no reports concerning the effect of vonoprazan on the tacrolimus blood concentration in liver transplant (LT) recipients. PATIENTS AND METHODS: Eighteen living donor liver transplantation (LDLT) recipients who switched from proton pump inhibitors (PPIs) to vonoprazan between 2016 to 2018 were enrolled in this retrospective study. We investigated blood levels of tacrolimus, and liver and renal function before and after the change from PPIs to vonoprazan. RESULTS: The median C 0 /D of tacrolimus before conversion, 3 months after conversion, and 6 months after conversion were 2.33, 1.53, and 1.89, respectively, and there was no significant difference. Conversion from another PPI to vonoprazan was not associated with a worsening liver function. The estimated glomerular filtration rate was significantly worse after conversion. CONCLUSION: Vonoprazan can be safely administered to LT recipients receiving tacrolimus during the stable period.

Liver transplantation for intrahepatic and hilar cholangiocellular carcinoma: Most recent updates in the literature.

Liver transplantation (LT) for non-hepatocellular carcinoma is still a debatable indication. Recently, hilar cholangiocellular carcinoma (hCCC) has attracted interest as a new indication for LT, but LT in this case should be carefully considered. Based on the recent meta-analysis for intrahepatic CCC (IHCCC) and our results from incidental IHCCC transplanted for other diseases such as primary sclerosing cholangitis, the indication for LT for IHCCC should be limited to a single tumor less than 2 cm. For hCCC, with pre-transplant chemoradiotherapy and careful selection criteria, long-term survival after LT could be attained. In order to improve the results of LT for intrahepatic and hCCC, further studies are required on the ingenuity of immunosuppressive therapy combined with chemotherapy, and optimal treatment methods to prevent recurrence, as well as initial case selection.

Long-term outcomes of living-donor liver transplantation, hepatic resection, and local therapy for hepatocellular carcinoma with three <3-cm nodules in a single institute.

Background and Aim: Treatment for small hepatocellular carcinoma (HCC) is determined based on the results of a liver function test and the tumor location and spread. The present study compared the outcomes among local therapy, hepatic resection (HR), and living-donor liver transplantation (LDLT) for small HCC in a single institute. Methods: We compared the overall survival, recurrence-free survival, and cancer-specific survival rates in patients with three HCC nodules <3 cm in size among local therapy, which included radiofrequency ablation (RFA), percutaneous ethanol injection (PEI), and transarterial chemoembolization (TACE), and surgical treatment (HR and LDLT). Results: One hundred and ninety-seven patients with local therapy (109 RFA, 26 PEI, and 78 TACE), 107 with HR, and 66 with LDLT were enrolled in this study. There was no significant difference in OS among these groups. The recurrence-free, cancer-specific survival (CSS) of LDLT was superior to local therapy and HR. The prognostic factors for the survival were Child-Pugh (CP) Grade B and tumor marker for local therapy and multiple tumors and elevated ALT levels for HR. Conclusions: For CP grade B patients with HCC of three <3-cm nodule, LDLT could be considered because it resulted in better survival and CSS rates than local therapy.

The Efficacy of Acoustic Radiation Force Impulse Elastography for Predicting Clinical Outcomes in Living Donor Liver Transplant.

PURPOSE: Acoustic radiation force impulse (ARFI) elastography is widely used for evaluating liver fibrosis. Here we evaluated the efficacy of ARFI elastography for estimating graft quality and clinical outcomes in living donor liver transplant (LDLT). METHODS: We retrospectively evaluated the cases of 87 LDLT donors who preoperatively underwent ARFI elastography at Nagasaki University Hospital between August 2010 and June 2016. We analyzed whether the velocity of shear wave (Vs) obtained by ARFI elastography affected the regeneration rate of each donor's remnant liver and the 1-year survival rate of the recipients. RESULTS: There were no significant correlations between Vs value and the donors' age. Only 1 donor (1.1%) showed significant fibrosis, F2 (portal fibrosis with few septa) in zero-biopsy. The 7 donors (8.0%), including 1 case, showed a high Vs value (> 1.33) that was equal to F2, although there was no abnormal pathologic finding except in 1 case. In those cases, the regeneration rate of the remnant liver after hepatectomy was significantly lower compared to other cases. The 1-year survival rate of the recipients paired with the high-Vs donors was also significantly poorer than that of the other cases (high-Vs: 57.1%, others: 84.2%, P = .04). CONCLUSIONS: ARFI elastography might be an effective examination for the preoperative evaluation of the graft quality in LDLT.

Recurrent Cytomegalovirus Infection Controlled by the Introduction of Everolimus in a Simultaneous Pancreas-Kidney Transplantation Recipient: A Case Report.

In simultaneous pancreas-kidney transplantation (SPK) recipients, cytomegalovirus (CMV) infection is a major complication that has been associated with the use of tacrolimus (TAC)-based immunosuppression. As one of the immunosuppressive drug options, the use of mammalian target of rapamycin inhibitors (mTORi) results in reduced rates of CMV infection in the field of solid organ transplantation. However, little is known about mTORi usage in pancreas transplantation. We report a case of recurrent CMV infection that was controlled by the introduction of mTORi (everolimus) in addition to a TAC-based immunosuppression regimen in SPK. A 52-year-old man underwent SPK. Graft duodenal perforation occurred on the 13th day of surgery, and graft duodenal resection was performed after long-term abscess drainage treatment. After graft duodenal resection, he was diagnosed with CMV viremia, and valganciclovir was started. However, because of recurrent febrile neutropenia caused by cytopenia as a side effect of valganciclovir, there was a repeated need for granulocyte-colony stimulating factor treatment. Immunosuppressive drug taper adjustment was attempted to control recurrent CMV viremia, and everolimus was introduced with the aim of reducing the dose of TAC and mycophenolate mofetil. This resulted in a continuously negative CMV antigenemia test and a stable general condition. Understanding the characteristics of various immunosuppressive agents and appropriately controlling and managing infectious diseases is crucial for the good postoperative management of patients with SPK.

Living Donor Liver Transplantation With Augmented Venous Outflow and Splenectomy: A Promised Land for Small Left Lobe Grafts.

OBJECTIVE: Living donor liver transplantation (LDLT) using small grafts, especially left lobe grafts (H1234-MHV) (LLG), continues to be a challenge due to small-for-size syndrome (SFSS). We herein demonstrate that with surgical modifications, outcomes with small grafts can be improved. METHODS: Between 2012 and 2020, we performed 130 adult LDLT using 61 (47%) LLG (H1234-MHV) in a single Enterprise. The median graft-to-recipient weight ratio was 0.84%, with graft-to-recipient weight ratio <0.7% accounting for 22%. Splenectomy was performed in 72 (56%) patients for inflow modulation before (n=50) or after (n=22) graft reperfusion. In LLG-LDLT, venous outflow was achieved using all three recipient hepatic veins. In right lobe graft (H5678) (RLG)-LDLT, the augmented graft right hepatic vein was anastomosed to the recipient's cava with a large cavotomy. Outcome measures include SFSS, early allograft dysfunction (EAD), and survival. RESULTS: Graft survival rates at 1, 3, and 5 years were 94%, 90%, and 83%, respectively, with no differences between LLG (H1234-MHV) and RLG (H5678). Splenectomy significantly reduced portal flow without increasing the complication rate. Despite the aggressive use of small grafts, SFSS and EAD developed in only 1 (0.8%) and 18 (13.8%) patients, respectively. Multivariable logistic regression revealed model for end-stage liver disease score and LLG (H1234-MHV) as independent risk factors for EAD and splenectomy as a protective factor (odds ratio: 0.09; P =0.03). For LLG (H1234-MHV)-LDLT, patients who underwent prereperfusion splenectomy tended to have better 1-year graft survival than those receiving postreperfusion splenectomy. CONCLUSIONS: LLG (H1234-MHV) are feasible in adult LDLT with excellent outcomes comparable to RLG (H5678). Venous outflow augmentation and splenectomy help lower the threshold of using small-for-size grafts without compromising graft survival.

Helicobacter bilis infection induces oxidative stress in and enhances the proliferation of human cholangiocytes.

BACKGROUND: Helicobacter bilis, an enterohepatic Helicobacter species, represents a carcinogenic risk factor for cholangiocytes owing to the prevalence of infections in patients with biliary tract cancer, cholecystitis, and pancreaticobiliary maljunction. However, the effect of H. bilis infection on cholangiocytes and the process and mechanism of carcinogenesis are not known. We aimed to determine the effects of H. bilis on cholangiocytes, focusing on inflammation and oxidative stress. MATERIALS AND METHODS: Helicobacter bilis and MMNK-1 cells were cocultured for 24 h and inflammatory cytokine secretion was evaluated. Furthermore, MMNK-1 cell proliferation, intracellular reactive oxidant species (ROS) production, and DNA damage caused by ROS were investigated. All factors were compared with and without H. bilis infection. RESULTS: Interleukin (IL)-6 and IL-8 secretion were significantly increased in MMNK-1 cocultures with H. bilis (IL-6, 24.3 ± 12.2 vs. 271.1 ± 286.4 pg/ml; IL-8, 167.6 ± 78.7 vs. 1085.1 ± 1047.1 pg/ml, p < .05). MMNK-1 proliferation was also significantly higher in H. bilis cocultures (1.05 ± 0.02 vs. 1.00-fold, respectively; p < .05). Coculturing enhanced the production of ROS in MMNK-1 cells depending on the cell concentration of H. bilis (1.0 vs. 1.17 ± 0.06, p < .05); however, DNA injury was not observed in cocultures with H. bilis (5.35 ± 0.87 vs. 6.08 ± 0.55 pg/µl, p = .06). CONCLUSIONS: Helicobacter bilis infection induced ROS production in and enhanced the proliferation of cholangiocytes.

Prognostic Impact of Relative Dose Intensity of Adjuvant Chemotherapy With S-1 on Pancreatic Ductal Adenocarcinoma.

BACKGROUND/AIM: Although adjuvant chemotherapy (AC) with S-1 is currently the standard treatment for pancreatic ductal adenocarcinoma (PDAC) in Japan, the associations between its relative dose intensity (RDI) and survival outcomes remain unclear. PATIENTS AND METHODS: We reviewed 310 patients with PDAC who had undergone pancreatectomy from January 2014 to June 2020 at three institutions. Of these, patients who had received adjuvant S-1 monotherapy were analyzed. Patients who had died or developed recurrences within 6 months, or received neoadjuvant chemotherapy, were excluded from the analyses. Possible predictors of overall survival (OS), including RDI, were analyzed using Cox regression. The cutoff value for RDI was determined by receiver operating characteristic analysis. RESULTS: Ninety-four patients with a median age of 69 years (range=39-84 years) were analyzed. In the high-RDI group (RDI≥72.3%, n=74), the OS rates were 98.5% and 80.8% at 1 and 3 years, respectively, whereas in the low-RDI group (RDI <72.3%, n=20) they were 88.9% and 51.6%, respectively (p=0.001). By multivariate analysis, lymph node metastasis [hazard ratio (HR)=3.06; p=0.020], low RDI (HR=2.95; p=0.020), and time interval from surgery to initiation of AC > 51 days (HR=2.50; p=0.046) were independently associated with inferior OS. The combination of the latter two factors clearly stratified both OS and recurrence-free survival (p<0.001 and p=0.017, respectively). CONCLUSION: Early initiation and maintenance of RDI of S-1 monotherapy after pancreatectomy may improve the OS of PDAC patients.