Liver Resection Under Total Hepatic Vascular Exclusion with In Situ Hypothermic Isolated Hepatic Perfusion for Advanced Liver Tumors.

PURPOSE: Continuous dissection or simultaneous reconstruction of the hepatic vein (HV) and inferior vena cava (IVC) was achieved under total hepatic vascular exclusion (THVE) with in situ hypothermic isolated hepatic perfusion (HIHP) in two cases. CASE 1: The patient previously underwent liver resections with the right HV for colorectal liver metastasis (CRLM). This time, the CRLM had invaded the left HV and IVC, and five courses of FOLFILI plus ramucirumab were given, resulting in stable disease. Due to expected high HV pressure, liver parenchymal transection was started under THVE. Sub-segmentectomy with patch graft plasty of the IVC and reconstruction of the left HV using a jugular vein graft were performed under THVE and HIHP. This patient died at home 3 months after surgery; the cause of death was unknown. CASE 2: Hepatocellular carcinoma in the caudate lobe was in extensive contact with the roots of three main HVs and the IVC, and pressed the hepatocaval confluence, with high HV pressure expected. In addition, tumor thrombosis extended to both the main portal vein and the common bile duct, resulting in the inability to introduce chemotherapy. After tumor thrombectomy, liver parenchymal transection was started under THVE. Extended left hepatectomy with wedge resection, and primary suture of the right HV and IVC was performed under THVE and HIHP. Recurrence-free and overall survivals were 8 months (lung metastasis) and 31 months, respectively. CONCLUSIONS: In liver resection for liver tumors located in the hepatocaval confluence, THVE with HIHP is useful for ensuring the safety.

Laparoscopic Left Hepatectomy with Resection of the Spiegel Lobe Using the Modified Caudate Lobe-First Approach.

BACKGROUND: Laparoscopic left hepatectomy with resection of the Spiegel lobe remains a technically demanding procedure as it is a deep-seated area surrounding the inferior vena cava (IVC). Mobilization of the Spiegel lobe requires safe exposure of the ventral side of the IVC while dissecting the short hepatic veins from the IVC. Additionally, wide space is needed to isolate the left Glissonean pedicle (Glt). We used a modified caudate lobe-first approach to overcome this challenge Maeda (J Hepato-Bil Pancreat Sci 25:335-41, 2018), Li (J Gastrointest Surg 23:1084-5, 2019), Homma (Surg Endosc 33:3851-7, 2019). METHODS: The ischemic area was confirmed after isolating the left and middle hepatic artery and left portal vein. After mobilizing the left lateral section, the Spiegel lobe was divided from the notch, which is the boundary between the caudate lobe and the Spiegel lobe, toward the middle hepatic vein (MHV). The Spiegel lobe was safely detached from the IVC with a short hepatic vein transected with the caudo-dorsal view. The Glt could be easily isolated due to the wide space on the ventral side of the IVC. After dividing the left hepatic duct, the MHV was exposed continuously from the root to the periphery, and parenchymal transection was completed by connecting the demarcation line and MHV. RESULTS: The total operation time was 430 min, and estimated blood loss was minimal. The patient was discharged on postoperative day 6 without complications. CONCLUSIONS: The modified caudate lobe-first approach can be used to safely perform laparoscopic left hepatectomy combined with the Spiegel lobe resection.

Laparoscopic Anatomic Liver Resection of the Dorsal Part of Segment 8 Using an Hepatic Vein-Guided Approach.

BACKGROUND: Laparoscopic anatomic liver resection is considered highly challenging, especially in segment 8 (S8), owing to the limited angle of the laparoscope and limited manipulation of the surgical instrument1,2. Additionally, resection is technically difficult when approaching the more peripheral branches since the Glissonean pedicle of S8 has several variations3 and is far from the hepatic hilum. The hepatic vein (HV)-guided approach involves entering from the cranial side of the liver while overcoming these difficulties with the unique view and techniques of laparoscopy4,5. We describe laparoscopic anatomic resection of the dorsal part of S8 using the HV-guided approach for hepatocellular carcinoma. METHODS: The drainage vein of segment 8 (V8), which often runs between the ventral and dorsal parts of S86,7, was exposed from the confluence of the middle HV to the periphery. The dorsal Glissonean branch of S8 (G8dor) was identified by deep dissection of the parenchyma on the right side of the V8. The right HV (RHV) was exposed toward the periphery after dissecting the G8dor. Liver parenchymal dissection was completed by connecting the demarcation line and the RHV. RESULTS: The total operation time was 319 min, estimated blood loss was 5 mL, and the patient was discharged on postoperative day 6 with no complications. CONCLUSION: Laparoscopic anatomic resection of the dorsal parts of S8 could be safely performed by exposing the HVs from their roots and using the HVs as a landmark to identify the intrahepatic Glissonean pedicles.

Intrahepatic Glissonean Approach for Laparoscopic Bisegmentectomy 7 and 8 With Root-Side Hepatic Vein Exposure.

BACKGROUND: Laparoscopic anatomic liver resections of the posterosuperior segments are technically demanding procedures.1-5 The segments are located in a deep-seated area of the liver surrounded by the ribs and the diaphragm, making forceps manipulation difficult. To overcome this limitation, an intrahepatic Glissonean approach and exposure of the hepatic veins from the root side was applied.6-10 The authors describe the technical aspects of performing a bisegmentectomy 7-8. METHODS: Liver parenchymal transection was initiated from the ventral aspect of the root of the middle hepatic vein, which often runs in the intersegmental plane, identifying the Glissonean pedicle of segment 8 (G8). After dissection of the G8, segmentectomy 8 was performed through identification of the ischemic area. After complete mobilization of the right lobe, the Glissonean pedicle of segment 7 (G7), which runs relatively near the liver surface,9, 10 was marked using ultrasonography. After division of the G7, a wide dissection between the caudate lobe and segment 7 was performed and connected to the previously dissected plane from the dorsal side of the right hepatic vein (RHV). Finally, bisegmentectomy 7-8 was performed with RHV resection because of tumor invasion. RESULTS: The operation time was 510 min, and the estimated blood loss was 150 ml. The patient was discharged on postoperative day 10 without any complications. CONCLUSIONS: Application of the intrahepatic Glissonean approach and exposure of the major hepatic veins from their roots using unique laparoscopic principles allows a safe performance of bisegmentectomy 7-8.

Outcomes and management of delayed complication after severe blunt liver injury.

BACKGROUND: The treatment of delayed complications after liver trauma such as bile leakage (BL) and hepatic artery pseudoaneurysms (HAPs) is difficult. The purpose of this study is to investigate the outcomes and management of post-traumatic BL and HAPs. METHODS: We retrospectively evaluated patients diagnosed with blunt liver injury, graded by the American Association for the Surgery of Trauma Liver Injury Scale, who were admitted to our hospital between April 2010 and December 2019. Patient characteristics and treatments were analyzed. RESULTS: A total of 176 patients with blunt liver injury were evaluated. Patients were diagnosed with grade I-II liver injury (n = 127) and with grade III-V injury (n = 49). BL was not observed in patients with grade I-II injury. Eight patients with grade III-V injury developed BL: surgical intervention was not needed for six patients with peripheral bile duct injury, but hepaticojejunostomy was needed for two patients with central bile duct injury. Out of 10 patients with HAPs, only three with grade I-II injury and one with grade III-V were treated conservatively; the rest six with grade III-V injury required transcatheter arterial embolization (TAE). All pseudoaneurysms disappeared. CONCLUSIONS: Severe blunt liver injury causing peripheral bile duct injury can be treated conservatively. In contrast, the central bile duct injury requires surgical treatment. HAPs with grade I-II injury might disappear spontaneously. HAPs with grade III-V injury should be considered TAE.

Short-term outcomes of laparoscopic versus open liver resection for hepatocellular carcinoma in older patients: a propensity score matching analysis.

BACKGROUND: The incidence of hepatocellular carcinoma (HCC) requiring surgical treatment in older patients has been continuously increasing. This study aimed to examine the safety and feasibility of performing laparoscopic liver resection (LLR) versus open liver resection (OLR) for HCC in older patients at a Japanese institution. METHODS: Between January 2010 and June 2021, 133 and 145 older patients (aged ≥ 70 years) who were diagnosed with HCC underwent LLR and OLR, respectively. Propensity score matching (PSM) analysis with covariates of baseline characteristics was performed. The intraoperative and postoperative data were evaluated in both groups. RESULTS: After PSM, 75 patients each for LLR and OLR were selected and the data compared. No significant differences in demographic characteristics, clinical data, and operative times were observed between the groups, although less than 10% of cases in each group underwent a major resection. Blood loss (OLR: 370 mL, LLR: 50 mL; P < 0.001) was lower, and the length of postoperative hospital stay (OLR: 12 days, LLR: 7 days; P < 0.001) and time to start of oral intake (OLR: 2 days, LLR: 1 day; P < 0.001) were shorter in the LLR group than in the OLR group. The incidence of complications ≥ Clavien-Dindo class IIIa was similar between the two groups. CONCLUSIONS: LLR, especially minor resections, is safely performed and feasible for selected older patients with HCC.

Safety and Effectiveness of Aortic Occlusion for Those Undergoing Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA): A Retrospective Single-Center Study.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is used to temporarily control bleeding and maintain the cerebral and coronary blood flow in cases in which it is difficult to control hemorrhagic shock. However, the safety and effectiveness of REBOA remains uncertain. OBJECTIVES: This study aimed to estimate the safety and effectiveness of aortic occlusion in patients who undergo REBOA catheter placement. METHODS: We conducted a retrospective study of patients who underwent REBOA catheter placement at Fukuyama City Hospital Emergency Medical Center from August 1, 2008 to March 31, 2020. A propensity score-matching analysis was used to compare 30-day survival between patients who undergo REBOA catheter placement with and without aortic occlusion. RESULTS: Overall, 122 of the 147 who underwent REBOA catheter placement at Fukuyama City Hospital were eligible for inclusion. Thirty-five patients in the Occlusion group and 35 patients in the Nonocclusion group were selected by propensity score matching. According to the 30-day survival rate, the difference between the two groups was not statistically significant (p = 0.288 log-rank test). Moreover, the required treatment, the types and incidence of complications, and other outcomes did not differ according to the presence or absence of aortic occlusion in patients who underwent REBOA catheter placement. CONCLUSION: According to the results of this study, in trauma patients who undergo REBOA catheter placement, the presence of aortic occlusion was not significantly associated with 30-day mortality. Furthermore, the performance of aortic occlusion was not associated with a significant increase in complications.

How-I-do-it: laparoscopic left medial sectionectomy utilizing a cranial approach to the middle hepatic vein and Laennec's capsule.

BACKGROUND: Laparoscopic anatomic liver resection is technically demanding, given the need to safely isolate the Glissonean pedicles and expose the hepatic veins (HVs) on the liver parenchyma cut surface. Laennec's capsule is observed around the Glissonean pedicles and root of the HVs. However, its existence, particularly on the peripheral side of the HVs, remains controversial. Herein, we describe Laennec's capsule-related histopathological findings around the HVs and a safe laparoscopic left medial sectionectomy utilizing Laennec's capsule. METHODS: The extrahepatic Glissonean approach was performed by connecting Gates II and III, in accordance with Sugioka's Gate theory. Liver parenchymal transection commenced along the demarcation line, which is between the medial and lateral sections, and the G4 was dissected during transection. Subsequently, via the outer-Laennec approach, the middle hepatic vein (MHV) was exposed from the root side in cranial view, while Laennec's capsule was preserved. Parenchymal transection was completed while connecting the MHV with the demarcation line. We obtained the membrane surrounding the HVs and performed histopathological examinations. RESULTS: Six patients underwent laparoscopic left medial sectionectomy from February 2012 to November 2020. There were no cases involving complications (Clavien-Dindo classification; grade II or higher), open-surgery conversion, transfusion, or surgery-related death. The histopathological findings showed Laennec's capsule surrounding both the trunk of the major HVs and the peripheral side of the HVs. CONCLUSIONS: A cranial approach to the major HVs utilizing Laennec's capsule is a feasible and advantageous procedure for laparoscopic left medial sectionectomy. We propose that Laennec's capsule surrounds the entire length of the HVs.

[Case of Gastric Malignant Lymphoma Invading Other Organs with Bleeding Treated by Surgery].

A female in her late 50s experienced dyspnea and was transported by an ambulance. Her hemoglobin score was low, and CT imaging showed a giant tumor in her stomach. The tumor perforated her liver and invaded the abdominal wall and duodenum around the Treitz ligament. She required surgery because of the massive hemorrhage due to the tumor. Total gastrectomy with lateral segmentectomy of the liver and resection of the duodenum and the ileum around the Treitz ligament were performed. At 1.5 months after surgery, chemotherapy for malignant lymphoma was successfully initiated.

[Use of a somatostatin analog to improve a patient's condition and the subsequent diagnosis of pancreatic VIPoma:a case report].

A 68-year-old woman with an 11-day history of sudden abdominal pain and severe watery diarrhea was transferred to our hospital due to an exacerbation of renal function despite hydration. After treatment for dehydration and acidemia was provided in our intensive care unit, patient's renal function improved. Contrast-enhanced abdominal computed tomography was finally performed, revealing a hypervascular pancreatic mass with multiple hepatic masses. This imaging finding along with her clinical symptoms indicated watery diarrhea hypokalemia achlorhydria (WDHA) syndrome caused by a pancreatic VIPoma. Somatostatin analog was administered immediately leading to the improvement of her diarrhea and her general condition. As a result, endoscopic ultrasonography-guided fine-needle aspiration could be performed. Consequently, she was diagnosed with a pancreatic neuroendocrine tumor. She then underwent surgical resection of the pancreatic tumor and liver metastasis. As revealed in the immunohistochemical analysis of the excised tumor tissue, VIP was highly expressed, resulting in the final diagnosis of pancreatic VIPoma. Therefore, the immediate use of a somatostatin analog is crucial for improving the patient's general condition and achieving a definitive diagnosis pathologically when a patient is suspected of having a pancreatic VIPoma.

Advanced hepatocellular carcinoma with hepatic vein tumor thrombosis and renal dysfunction after hepatic arterial infusion chemotherapy effectively treated by liver resection with active veno-venous bypass: report of a case.

BACKGROUND: Hepatocellular carcinoma (HCC) patients with hepatic vein tumor thrombosis (HVTT) extending to the inferior vena cava (IVC) have an extremely poor prognosis. Here we report a case of HCC with HVTT and renal dysfunction after hepatic arterial infusion chemotherapy (HAIC) successfully treated by liver resection and active veno-venous bypass. CASE PRESENTATION: A 77-year-old man was diagnosed to have a large HCC with intrahepatic metastases and HVTT extending to the IVC. Due to the advanced stage, HAIC with cisplatin was performed 13 times in a period of 17 months. As a consequence of this treatment, the size of the main HCC markedly decreased, and the advanced part of the HVTT went down to the root of the right hepatic vein (RHV). However, because of renal dysfunction, HAIC with cisplatin was discontinued and right hepatectomy with patch graft venoplasty of the root of the RHV was performed. Because progression of renal dysfunction had to be avoided, veno-venous bypass was activated during IVC clamping to prevent renal venous congestion and hypotension. Histological examination showed foci of a moderately differentiated HCC with extensive fibrosis and necrosis in the main HCC. Histologically, the HVTT in the RHV showed massive necrosis and tightly adhered to the vascular wall of the RHV. The postoperative function of the remnant liver was good, and no further deterioration of renal function was detected. The patient did not show signs of recurrence 15 month after surgery. CONCLUSION: In the present case, HAIC using cisplatin in combination with hepatic resection and patch graft venoplasty of the IVC provided a good long-term outcome with no HCC recurrence. Renal function was preserved by using active veno-venous bypass during IVC clamping to prevent renal venous congestion and hypotension.

A case of pancreatic arteriovenous malformation identified by investigating the cause of upper abdominal pain associated with acute pancreatitis.

A man in his 60s with epigastric pain was diagnosed with acute pancreatitis and subsequently recovered following conservative treatment. However, because of repeated upper abdominal pain and the formation of a pancreatic pseudocyst, he was transferred to our institution for evaluation. Dynamic computed tomography (CT) scanning confirmed abnormal vessels in the tail of the pancreas and early venous return to the splenic vein in the early arterial phase. Abdominal angiography revealed a racemose vascular network in the tail of the pancreas, confirming the presence of an arteriovenous malformation (AVM) in this region. This AVM was thought to be the cause of the acute pancreatitis, so a distal pancreatectomy was performed. The patient's postoperative course was uneventful, and there has been no recurrence at the 7-month postoperative follow-up. Surgical resection has a low recurrence rate and good outcome;thus, if a pancreatic AVM appears difficult to treat with conservative medical therapy, surgical resection appears to be the definitive treatment.

Correlation of computed tomography imaging features and pathological features of 41 patients with pancreatic neuroendocrine tumors.

BACKGROUND/AIMS: Pancreatic neuroendocrine tumors (PNET) are relatively rare. Here, we present clinical and pathological characteristics of PNETs to show a relationship between computed tomography (CT) imaging and the 2010 World Health Organization (WHO) classification. METHODOLOGY: We retrospectively reviewed the records of 41 PNET patients who were treated between 2002 and 2012. All tumors were classified as neuroendocrine tumor (NET) grade 1 (G1), NET grade 2 (G2), or neuroendocrine carcinoma (NEC) grade 3 (G3) on the basis of the 2010 WHO classification system. RESULTS: Twenty-five tumors were classified as G1, 11 as G2, and five as G3. Mean sizes of the G1, G2 and G3 tumors were 1.84 ± 0.54, 4.90 ± 0.84, and 5.62 ± 1.18 cm, respectively, (P < 0.01). A PNET is typically hypervascular and exhibits contrast enhancement on enhanced CT. Higher percentage of G1 tumors demonstrated typical imaging and showed a significantly greater distinct mass compared with G2 and G3 tumors. CONCLUSIONS: Although PNET has many imaging features that appear on CT, G2 and G3 tumors often show atypical imaging features, particularly with large sizes and/or ill-defined features, when compared with G1 tumors. If a PNET has atypical imaging features, possibility of malignancy should be considered.

Enlarging lymphoepithelial cyst of the pancreas during 12 months of observation: report of a case.

Pancreatic lymphoepithelial cysts (LECs) are rare benign pancreatic cystic lesions, the etiology of which is unknown. We report a case of a pancreatic LEC, discovered incidentally in a 63-year-old man during a follow-up clinic visit for an abdominal aneurysm. Computed tomography showed a multilocular cyst, 60-mm diameter in the body of the pancreas. This cyst increased from 6.0 to 6.5 cm during 12 months of observation. Part of the cyst was also visualized on positron emission tomography imaging. Since a pancreatic cystic neoplasm could not be ruled out, we performed distal pancreatectomy and postoperative pathological examination confirmed that the lesion was an LEC of the pancreas. Despite the conclusive postoperative findings, resection is unavoidable when a true pancreatic neoplasm cannot be excluded.

Double-balloon enteroscopy for choledochojejunal anastomotic stenosis after hepato-biliary-pancreatic operation.

BACKGROUND AND AIM: There have been few reports on the success rate of balloon dilation and stent deployment using endoscopic retrograde cholangiopancreatography by double-balloon enteroscopy (DBE-ERCP) or on the follow-up period after stent removal in patients with a reconstructed digestive tract and stenosis of choledochojejunal anastomosis. The present study was designed to evaluate the usefulness of DBE-ERCP in patients with a reconstructed digestive tract and stenosis of choledochojejunal anastomosis. METHODS: Forty-four patients with stenosis of choledochojejunal anastomosis underwent DBE-ERCP at Okayama University Hospital between April 2008 and January 2012 (107 procedures). Rates of reaching choledochojejunal anastomosis, stent deployment, and restenosis after stent removal were retrospectively evaluated. RESULTS: Insertion of DBE into the choledochojejunal anastomotic site succeeded in 38 of 44 patients (86.4%), and anastomotic dilation and stent deployment succeeded in 36 of 44 patients (81.8%). In 32 of 44 patients (72.7%), their anastomotic stenoses were improved, and they achieved stent removal. After stent removal, restenosis of choledochojejunal anastomosis was detected in seven of 32 patients; however, the resolution of restenosis was achieved in all seven of those patients. CONCLUSION: Dilation of choledochojejunal anastomosis combined with stent deployment using DBE-ERCP seems to be a viable first-line treatment for patients with stenosis of choledochojejunal anastomosis.

First successful case of simultaneous liver and kidney transplantation for patients with chronic liver and renal failure in Japan.

Establishment of a preferential liver allocation rule for simultaneous liver and kidney transplantation (SLK) and revisions of laws regarding organ transplants from deceased donors have paved the way for SLK in Japan. Very few cases of SLK have been attempted in Japan, and no such recipients have survived for longer than 40 days. The present report describes a case of a 50-year-old woman who had undergone living donor liver transplantation at the age of 38 years for management of post-partum liver failure. After the first transplant surgery, she developed hepatic vein stenosis and severe hypersplenism requiring splenectomy. She was then initiated on hemodialysis (HD) due to the deterioration of renal function after insertion of a hepatic vein stent. She was listed as a candidate for SLK in 2011 because she required frequent plasma exchange for hepatic coma. When her Model for End-stage Liver Disease score reached 46, the new liver was donated 46 days after registration. The reduced trisegment liver and the kidney grafts were simultaneously transplanted under veno-venous bypass and intraoperative HD. The hepatic artery was reconstructed prior to portal reconstruction in order to shorten anhepatic time. Although she developed subcapsular bleeding caused by hepatic contusion on the next day, subsequent hemostasis was obtained by transcatheter embolization. Thereafter, her recovery was uneventful, except for mild rejection and renal tubular acidosis of the kidney graft. This case highlights the need to establish Japanese criteria for SLK.

Risk factors of morbidity and predictors of long-term survival after hepatopancreatoduodenectomy for biliary cancer.

BACKGROUND/AIMS: Hepatopancreatoduodenectomy (HPD) is performed to achieve radical resection of malignant biliary tumors. We reviewed clinical outcomes to evaluate the utility of HPD in terms of morbidity and mortality. METHODOLOGY: A retrospective analysis was conducted on 17 patients underwent HPD between August 1991 and May 2013; 9 bile duct cancer, 5 advanced gallbladder and 3 pancreatic tumor with liver metastasis. RESULTS: The morbidity and mortality rates were 88.3% and 0%, respectively. Univariate analysis showed that a body mass index of ≥22 and preoperative total bilirubin level ≥0.8 mg/dl were significantly associated with severe complications. One-, 3- and 5-year survival rate were 73.3%, 60.0% and 30.0%. In 14 patients with biliary carcinoma, univariate analysis showed that a histological grade of G1 was significantly associated with survival. Patients without pancreatic invasion or portal vein invasion tended to survive longer than patients with these types of invasion, although the difference was not significant. CONCLUSIONS: HPD can be performed with no mortality and provides a survival benefit for some patients with biliary carcinoma undergoing curative resection. In patients with grade G1 biliary carcinoma without pancreatic or portal vein invasion in particular, this aggressive surgery might offer a chance of long-term survival.

Hepatitis C virus-specific T-cell response correlates with hepatitis activity and donor IL28B genotype early after liver transplantation.

It is not known how the immune system targets hepatitis C virus (HCV)-infected HLA-mismatched hepatocytes under immune-suppressed conditions after orthotopic liver transplantation (OLT). In addition, the relationship between the HCV-specific immune response and IL28B variants as predictors of HCV clearance has not been well-characterized. We determined the IL28B polymorphisms for 57 post-OLT HCV carriers, and we assessed the HCV-specific immune responses by measuring the peripheral blood mononuclear cell-derived HCV-specific interferon-gamma (IFN-γ) response using an enzyme-linked immunospot assay. At 1-3 years after OLT, patients with no active hepatitis showed higher total spots on the immunospot assay. At＞3 years after OLT, patients with resolved HCV showed higher levels of core, NS3, NS5A, and total spots compared to the chronic hepatitis patients. The IL28B major genotype in the donors correlated with higher spot counts for NS5A and NS5B proteins at 1-3 years after OLT. In the post-OLT setting, the HCV-specific immune response could be strongly induced in patients with no active hepatitis with an IL28B major donor or sustained virological response. Strong immune responses in the patients with no active hepatitis could only be maintained for 3 years and diminished later. It may be beneficial to administer IFN treatment starting 3 years after OLT, to induce the maximum immunological effect.

Intratumoral peptide injection enhances tumor cell antigenicity recognized by cytotoxic T lymphocytes: a potential option for improvement in antigen-specific cancer immunotherapy.

Antigen-specific cancer immunotherapy is a promising strategy for improving cancer treatment. Recently, many tumor-associated antigens and their epitopes recognized by cytotoxic T lymphocytes (CTLs) have been identified. However, the density of endogenously presented antigen-derived peptides on tumor cells is generally sparse, resulting in the inability of antigen-specific CTLs to work effectively. We hypothesize that increasing the density of an antigen-derived peptide would enhance antigen-specific cancer immunotherapy. Here, we demonstrated that intratumoral peptide injection leads to additional peptide loading onto major histocompatibility complex class I molecules of tumor cells, enhancing tumor cell recognition by antigen-specific CTLs. In in vitro studies, human leukocyte antigen (HLA)-A*02:01-restricted glypican-3144-152 (FVGEFFTDV) and cytomegalovirus495-503 (NLVPMVATV) peptide-specific CTLs showed strong activity against all peptide-pulsed cell lines, regardless of whether the tumor cells expressed the antigen. In in vivo studies using immunodeficient mice, glypican-3144-152 and cytomegalovirus495-503 peptides injected into a solid mass were loaded onto HLA class I molecules of tumor cells. In a peptide vaccine model and an adoptive cell transfer model using C57BL/6 mice, intratumoral injection of ovalbumin257-264 peptide (SIINFEKL) was effective for tumor growth inhibition and survival against ovalbumin-negative tumors without adverse reactions. Moreover, we demonstrated an antigen-spreading effect that occurred after intratumoral peptide injection. Intratumoral peptide injection enhances tumor cell antigenicity and may be a useful option for improvement in antigen-specific cancer immunotherapy against solid tumors.

Risk factors for acute renal injury in living donor liver transplantation: evaluation of the RIFLE criteria.

Acute renal injury (ARI) is a serious complication after liver transplantation. This study investigated the usefulness of the RIFLE criteria in living donor liver transplantation (LDLT) and the prognostic impact of ARI after LDLT. We analyzed 200 consecutive adult LDLT patients, categorized as risk (R), injury (I), or failure (F), according to the RIFLE criteria. ARI occurred in 60.5% of patients: R-class, 23.5%; I-class, 21%; and F-class, 16%. Four patients in Group-A (normal renal function and R-class) and 26 patients in Group-B (severe ARI: I- and F-class) required renal replacement therapy (P < 0.001). Mild ARI did not affect postoperative prognosis regarding hospital mortality rate in Group A (3.2%), which was superior to that in Group B (15.8%; P = 0.0015). Fourteen patients in Group B developed chronic kidney disease (KDIGO stage 3/4). The 1-, 5- and 10-year survival rates were 96.7%, 90.6%, and 88.1% for Group A and 71.1%, 65.9%, and 59.3% for Group B, respectively (P < 0.0001). Multivariate analysis revealed risk factors for severe ARI as MELD ≥ 20 [odds ratio (OR) 2.9], small-for-size graft (GW/RBW <0.7%; OR 3.1), blood loss/body weight >55 ml/kg (OR 3.7), overexposure to calcineurin inhibitor (OR 2.5), and preoperative diabetes mellitus (OR 3.2). The RIFLE criteria offer a useful predictive tool after LDLT. Severe ARI, defined beyond class-I, could have negative prognostic impact in the acute and late postoperative phases. Perioperative treatment strategies should be designed and balanced based on the risk factors for the further improvement of transplant prognosis.