Impact of Liver Fibrosis Severity on Oncological Prognosis in Hepatocellular Carcinoma.

Introduction: Cirrhosis is deemed to be a contributing factor to the postoperative recurrence of hepatocellular carcinoma (HCC); however, the precise impact of liver fibrosis on both cancer-specific prognoses remains unclear. This investigation sought to elucidate the effect of liver fibrosis severity on the cancer-specific prognosis. Methods: A total of 524 consecutive patients were included. Recurrence-free survival (RFS) and disease-specific survival (DSS) were compared according to fibrosis stage. Moreover, postoperative outcomes were subjected to analysis in cohorts of patients with F0 and F1-3, as well as in those with F1-3 and F4, who were carefully matched for background factors. Results: The 5-year RFS exhibited a significantly worse outcome in the F4 group compared to other stages of fibrosis: 5-year RFS - F0 (46.6%), F1-3 (33.1%), and F4 (23.5%), p = 0.03 (F0 vs. F1-3) and p < 0.01 (F1-3 vs. F4). Additionally, the 5-year DSS also presented a significantly worse prognosis in the F4 group: 5-year DSS - F0 (82.9%), F1-3 (73.6%), and F4 (57.4%), p = 0.04 (F0 vs. F1-3) and p < 0.01 (F1-3 vs. F4). In multivariate analysis, fibrosis 1, 2, 3, and 4 stage (compared with F0) (HR: 1.70, 1.81, 1.89, and 3.99, 95% confidence interval: 1.10-1.99, 1.39-2.22, 1.41-2.55, and 2.25-5.01, p = 0.022, p = 0.008, p < 0.001, and p < 0.001, respectively) was independent risk factor for RFS. After matched analysis, both RFS and DSS exhibited significantly worse prognoses in the presence of more advanced fibrosis. There was a significantly higher incidence of multiple recurrences in the F4 group than the F1-3 group, and a number of recurrences were observed both in the same hepatic segment as the resected side and in the contralateral lobe in F4 group. Discussion/Conclusion: The hazard and recurrence pattern of HCC signifies that the prognosis could potentially be poor, as the hepatic fibrosis likely owing to a higher hepatocarcinogenic potential, even in the absence of progression to cirrhotic condition. The risk of de novo recurrence may also increase with the progression of this fibrosis.

Retro-pancreatic pull-through reconstruction of the hypoplastic portal vein using the autologous mesosystemic shunt vessel in adult living donor liver transplantation: a case report.

BACKGROUND: In liver transplant patients with hypoplastic portal vein (PV), when the narrowed segment is extended too deep into the dorsal side of the pancreas, it is difficult and dangerous to reconstruct the interposition graft from the upper part of the pancreas. Herein, we present a case of PV reconstruction with the autologous mesosystemic shunt vessel from the caudal side of the pancreas in a situation where the narrowed PV was deep, and we discuss the technical details. CASE PRESENTATION: A 25-year-old woman presented with cholestatic liver cirrhosis due to biliary atresia after Kasai procedure. Since her jaundice progressed, she was referred to our hospital for liver transplantation. Laboratory tests showed that her total bilirubin was elevated to 7.6 mg/dL. The Model for End-Stage Liver Disease score was 18, and the Child-Pugh score was 9 (Grade B). She underwent living donor liver transplantation (LDLT) using a right hemi-liver graft procured from her 54-year-old mother. The conventional approach from the cephalad side to the superior mesenteric vein (SMV) and splenic vein (SpV) confluence behind the pancreas was extremely difficult in this case because the confluence of SMV and SpV was close to the lower edge of the pancreas. Therefore, we decided to perform PV reconstruction from the caudal side. The main trunk of PV was documented as narrow (5 mm in diameter), for which retro-pancreatic pull-through PV reconstruction was successfully performed using her own mesosystemic shunt vessel. A contrast computed tomography (CT) scan was performed on postoperative day 5 because of an elevation of D-dimer and found a partial thrombus in the left pulmonary artery, as well as in the PV and left renal vein. Thereafter, thrombolytic therapy with low-molecular-weight heparin was started immediately and switched to a direct oral anticoagulant. The follow-up CT taken 3 months after liver transplantation revealed a patent PV without thrombus; therefore, anticoagulant therapy was discontinued. Currently, the patient has been well and active with a patent PV without anticoagulant therapy for 3 years after LDLT. CONCLUSIONS: Retro-pancreatic pull-through reconstruction of the hypoplastic PV is a feasible and effective method when conventional reconstruction is not indicated.

An Immunohistochemical Analysis of Osteopontin and S100 Calcium-binding Protein P is Useful for Subclassifying Large- and Small-duct Type Intrahepatic Cholangiocarcinomas.

Intrahepatic cholangiocarcinoma (iCCA) has been newly subclassified into two different subtypes: large-duct (LD) type and small-duct (SD) type. However, many cases are difficult to subclassify, and there is no consensus regarding subclassification criteria. LD type expresses the highly sensitive diagnostic marker S100 calcium-binding protein P (S100P), while SD type lacks sensitive markers. We identified osteopontin (OPN) as a highly sensitive marker for SD type. This study aimed to develop new subclassification criteria for LD-type and SD-type iCCA. We retrospectively investigated 74 patients with iCCA and subclassified them based on whole-section immunostaining of S100P and OPN. Of the 74 cases, 41 were subclassified as LD type, 32 as SD type, and one was indeterminate. Notably, all S100P-negative cases had OPN positivity. Seventy-three of the 74 cases (98.6%) were clearly and easily subclassified as LD or SD type using only these 2 markers. We also determined the value of immunohistochemistry in cases that were difficult to diagnose based on hematoxylin-eosin and Alcian blue-periodic acid-Schiff staining. Furthermore, we analyzed the clinicopathological characteristics and prognoses of these 2 subtypes. LD type was a poor prognostic factor on univariate analysis; it had significantly worse overall survival ( P = 0.007) and recurrence-free survival ( P < 0.001) than the SD type. In conclusion, we propose new subclassification criteria for iCCA based on immunostaining of S100P and OPN. These criteria may help pathologists to diagnose subtypes of iCCA, supporting future clinical trials and the development of medications for these 2 subtypes as distinct cancers.

Long-term remnant liver volume dynamics after major hepatectomy for perihilar cholangiocarcinoma following portal vein embolization.

BACKGROUND: Portal vein embolization (PVE) followed by major hepatectomy is a common treatment strategy for patients with perihilar cholangiocarcinoma (PHCC); however, the long-term dynamics of the liver remnant volume (LRV) remain unclear. Here, we report the dynamics of the LRV in patients who underwent hepatectomy following PVE. METHODS: A total of 39 patients with PHCC who underwent right hemihepatectomy or left trisectionectomy with extrahepatic bile duct resection between 2004 and 2021 were enrolled in this study [PVE (n = 27) and non-PVE (n = 12]). Long-term remnant liver dynamics were analyzed in propensity score-matched pairs (n = 10/group). RESULTS: The LRV/future liver remnant volume (FLRV) at 1 week to 1 month after hepatectomy were smaller in the PVE group than in the non-PVE group (1.53 vs. 1.69, p = .044 and 1.52 vs 1.99, p = .003, respectively). In the non-PVE group, the LRV/FLRV ratio plateaued 1-3 months postoperatively, whereas progressive hypertrophy occurred in the PVE group, and the LRV/FLRV ratio became equal in both groups at 1 year after hepatectomy (1.96 vs. 1.97; p = .799). Multivariate analysis revealed that FLRV/total liver volume (TLV) ≤ 0.43 was the only independent predictor of LRV/FLRV ≥1.9 at 1 year after hepatectomy (odds ratio:5.345, 95% confidence interval:1.210-23.615; p = .027). CONCLUSION: Although the long-term LRV was nearly equal in both groups, short-term LRV hypertrophy was lower in the PVE group than in the non-PVE group.

Usefulness of intratumoral perfusion analysis for assessing biological features of non-functional pancreatic neuroendocrine neoplasm.

PURPOSE: Here, we evaluated the usefulness of intratumoral perfusion analysis using preoperative contrast-enhanced CT (E-CT) to assess biological features of non-functional pancreatic neuroendocrine neoplasms (NF-PanNENs). METHODS: We retrospectively studied 44 patients who underwent curative surgery for NF-PanNENs. We used preoperative E-CT with compartment model analysis to calculate the tumor perfusion parameters K1 (inflow rate constant), 1/k2 (mean transit time), and K1/k2 (distribution volume). We assessed the association between perfusion parameters and biological features of NF-PanNENs, including the WHO classification tumor histopathological grade and prognosis after surgery. RESULTS: Patients in this study had a neuroendocrine tumor (NET) G1 (n = 32) or NET G2 (n = 12). Neither NET G3 or NEC tumors were observed. Among perfusion parameters, K1 was the most accurate predictor of the high-grade tumor (AUC: 0.726). K1-low (< 0.028 s-1) was significantly associated with large tumors (≥ 20 mm) (p = 0.022), high mitotic index (p = 0.017), high Ki-67 index (p = 0.004), and lymphatic invasion (p = 0.025). Synchronous extra-pancreatic metastasis, including lymph node metastasis or liver metastasis, more frequently developed in K1-low patients than in K1-high patients (29% vs 4%, p = 0.025). Disease-free survival of patients with a K1-low tumor was poorer than that of patients with a K1-high tumor (p = 0.005). Furthermore, no patient with a K1-high tumor developed recurrence after initial surgery. CONCLUSION: The perfusion parameters obtained using E-CT were significantly associated with biological features and prognosis of NF-PanNENs.

Juvenile polyposis syndrome with gastric and duodenal polyposis presenting with refractory anemia and protein-leakage gastroenteropathy in a patient with SMAD4 mutation: a case report.

BACKGROUND: Juvenile polyposis syndrome (JPS) is an autosomal dominant, inherited disorder characterized by multiple hyperproliferative polyps of the gastrointestinal tract, particularly of the colon, rectum, and stomach. SMAD4 mutations are frequently associated with multiple polyposis of the stomach; the condition causes severe bleeding and hypoproteinemia, which may progress to severe dysplasia and adenocarcinoma formation. We report our experience with the first case of total gastrectomy with pancreaticoduodenectomy following two partial jejunectomies for JPS, who presented with refractory anemia and protein-losing gastroenteropathy due to polyposis of the stomach and duodenum. CASE PRESENTATION: A 33-year-old Japanese man presented with the chief complaint of shortness of breath on exertion. His family history included gastric polyposis (mother, aunt, and cousin) and cerebral infarction (grandmother). Blood testing at the initial visit indicated iron-deficiency anemia, whereas endoscopy revealed multiple polyps in the duodenum and jejunum. Genetic testing revealed a 4 bp deletion (TGAA) in exon 5 of the SMAD4 gene; two partial small bowel resections were performed, but polyps grew in the remaining stomach, duodenum, and small intestine. The patient developed hypoalbuminemia and anemia, and required central venous nutrition and blood transfusion. However, because the hyponutrition and anemia remained poorly controlled, a total gastrectomy with concomitant pancreaticoduodenectomy was performed. Malnutrition and anemia improved, and there was no polyp recurrence in the remaining intestinal tract at 18 months after the surgery. CONCLUSIONS: We report a case of JPS with refractory anemia and protein-losing gastroenteropathy that was treated with total gastrectomy with concomitant pancreaticoduodenectomy. Although the surgery was highly invasive, the patient's nutritional status and anemia improved postoperatively, and the treatment was successful. However, to determine the appropriate surgical procedure, a detailed examination of the gastrointestinal lesions and the effects of the surgical invasion on nutritional status must be undertaken.

Intrahepatic Cholangiocarcinoma with High Microsatellite Instability and Tumor Mutation Burden That Responded Significantly to Pembrolizumab but Perforated within a Short Period.

Cholangiocarcinoma has a poor prognosis, and resection is the only curative treatment. Pembrolizumab, a programmed death receptor 1 inhibitor, has proven effective against unresectable or metastatic solid tumors with high microsatellite instability (MSI-H) or a high tumor mutation burden (TMB-H). In the present case, pembrolizumab treatment was initiated after standard chemotherapy for MSI-H and TMB-H unresectable intrahepatic cholangiocarcinoma. Intrahepatic tumor necrosis perforated the abdominal cavity. Emergency surgery was performed, but the patient died 36 days after admission. A pathological autopsy revealed that the intrahepatic tumor had almost completely disappeared.

Long-term Catch-up Growth and Risk Factors for Short Adult Height After Pediatric Liver Transplantation: A Retrospective Study.

BACKGROUND: Children requiring liver transplantation generally have severe growth retardation. Recipients experience posttransplantation catch-up growth, although some show short adult heights. We aimed to determine decades-long catch-up growth trends and risk factors for short adult height following liver transplantation. METHODS: We analyzed long-term height Z scores and risk factors for short adult height in a single-center retrospective cohort of 117 pediatric liver transplantation recipients who survived >5 y, with 75 of them reaching adult height. RESULTS: Median age at transplantation was 1.3 y, and the most common primary diagnosis was biliary atresia (76.9%). Mean height Z scores pretransplantation and 1, 3, and 8 y after transplantation were -2.26, -1.59, -0.91, and -0.59, respectively. The data then plateaued until 20 y posttransplantation when mean adult height Z score became -0.88, with a median follow-up of 18.6 y. Nineteen recipients did not show any catch-up growth, and one quarter of recipients had short adult height (<5th percentile of the healthy population). Multivariate analysis identified old age (odds ratio, 1.22 by 1 y; P = 0.002), low height Z scores at transplantation (odds ratio, 0.46 by 1 point; P < 0.001), and posttransplantation hospital stay ≥60 d (odds ratio, 4.95; P = 0.015) as risk factors for short adult height. In contrast, prolonged steroid use after transplantation was not considered a significant risk factor. CONCLUSIONS: Although tremendous posttransplantation catch-up growth was observed, final adult height remained inadequate. For healthy physical growth, liver transplantation should be performed as early as possible, before growth retardation becomes severe.

Utilization of muscle area in an accurate prediction formula for renal function for patients with hepatocellular carcinoma.

OBJECTIVE: Accurate assessment of renal function prior to surgery for hepatocellular carcinoma is important for patient outcome, but current methods such as the estimated glomerular filtration rate (eGFR) are inadequate. We developed a new prediction formula that incorporates preoperative computed tomography (CT) imaging data to determine renal function. METHODS: We retrospectively analyzed 400 patients who underwent hepatectomy for hepatocellular carcinoma between January 2010 and December 2021. Predictors associated with renal function were identified by multivariate analysis. RESULTS: Age, sex, body height, body weight, body surface area, body mass index, serum creatinine, and muscle areas including third lumbar vertebra total muscle area (L3 TMA) determined by preoperative CT were identified as independent predictors likely to be associated with renal function. These were used to construct a new prediction formula using multiple regression analysis performed with a stepwise method: 232.2 + (-1.17 × age) + (-89.0 × serum creatinine) + (0.28 × L3 TMA). The median difference between conventional eGFR and CCr was 47.6 ml/min (range, 1.7-137.9 ml/min), while that between the new eGFR and CCr was 14.3 ml/min (range, 0.02-64.7 ml/min). Spearman rank correlation analysis revealed that the new eGFR was more positively correlated with CCr than conventional eGFR (ρ = 0.623, P < 0.05; ρ = 0.700, P < 0.05, respectively), and hence more accurately reflected renal function. CONCLUSION: A new prediction formula based on L3 TMA determined by CT is more accurate than conventional eGFR for evaluating renal function.

The platelet-to-lymphocyte ratio is a complementary prognostic factor to tumor markers in predicting early recurrence of hepatocellular carcinoma after hepatectomy.

BACKGROUND: The usefulness of inflammation-based prognostic scores for early recurrence (ER) after hepatectomy for hepatocellular carcinoma has rarely been reported. This study aimed to evaluate the potential of inflammation-based prognostic scores as predictors of ER and their relationship with tumor markers. METHODS: We enrolled 338 patients who underwent hepatectomy for hepatocellular carcinoma between January 2007 and December 2021. Clinicopathological factors were compared between patients who developed ER (ER group) and those who did not develop ER (non-ER group). The association between inflammation-based prognostic scores and ER status was evaluated. These scores were compared with those of well-established tumor markers. RESULTS: The platelet-to-lymphocyte ratio (PLR) correlated with ER of hepatocellular carcinoma, with an area under the curve (AUC) value of 0.70, sensitivity of 68.1%, and specificity of 67.7%. In patients with low tumor marker levels, the PLR showed a strong correlation with ER of hepatocellular carcinoma, with an AUC value of 0.851, sensitivity of 100%, and specificity of 76.2%. Multivariate analysis revealed that the PLR was an independent prognostic factor for ER. CONCLUSIONS: The PLR is useful and complementary to tumor markers for predicting ER after hepatectomy for hepatocellular carcinoma.

Impact of sarcopenic obesity on post-hepatectomy bile leakage for hepatocellular carcinoma.

BACKGROUND: Post-hepatectomy bile leakage (PHBL) is a potentially fatal complication that can arise after hepatectomy. Previous studies have identified obesity as a risk factor for PHBL. In this study, we investigated the impact of sarcopenic obesity on PHBL in hepatocellular carcinoma (HCC) patients. METHODS: In total, we enrolled 409 patients who underwent hepatectomy without bilioenteric anastomosis for HCC between January 2010 and August 2021. Patients were grouped according to the presence or absence of PHBL. Patient characteristics, including body mass index and sarcopenic obesity, were then analyzed for predictive factors for PHBL. RESULTS: Among the 409 HCC patients included in the study, 39 developed PHBL. Male sex, hypertension, cardiac disease, white blood cell counts, the psoas muscle area, and visceral fat area, and intraoperative blood loss were significantly increased in the PHBL (+) group compared with the PHBL (-) group. Multivariate analysis showed that the independent risk factors for the occurrence of PHBL were intraoperative blood loss ≥370 mL and sarcopenic obesity. CONCLUSIONS: Our results show that it is important to understand whether a patient is at high risk for PHBL prior to surgery and to focus on reducing intraoperative blood loss during surgery for patients with risk factors for PHBL.

Antibody titer after administration of mRNA-based vaccine against severe acute respiratory syndrome coronavirus 2 in liver transplant recipients.

Introduction: The mRNA-based vaccine was released as a COVID-19 prophylactic; however, its efficacy in organ transplant recipients is unknown. This study aimed to clarify this in liver transplant recipients. Methods: Herein, liver transplant recipients from two hospitals who received vaccines were included. Immunoglobulin-G antibodies against the spike and nucleocapsid proteins were measured chronologically after the second, third, and fourth vaccine doses. Results: Antibody levels in 125 liver transplant recipients and 20 healthy volunteers were analyzed. The median age at transplant was 35 (interquartile range 1, 53) years, and the period between transplant and the first dose was 15.2 ± 7.7 years. After the second and third doses, 89.1% and 100% of recipients displayed a positive humoral response, respectively. Anti-spike antibodies after the second dose were significantly reduced at 3 and 6 months, compared to that at 1 month (26.0 [5.4, 59.5], 14.7 [6.5, 31.4] vs. 59.7 [18.3, 164.0] AU/mL, respectively, p < 0.0001). However, a booster vaccine significantly elevated anti-spike antibodies in LT recipients (p < 0.0001) as well as in healthy controls (p < 0.0001). Additionally, the decay rate was comparable between the transplant recipients and controls (2.1 [0.8, 4.5] vs. 2.7 [1.1, 4.1] AU/mL/day, p = 0.9359). Only 4.0% of vaccinated transplant recipients were positive for anti-nucleocapsid antibodies. Conclusion: Liver transplant recipients can acquire immunity similar to that of healthy people through vaccination against SARS-CoV-2. The antibody decay rate is the same, and booster vaccinations should be administered similarly to that in healthy individuals.

Increased mitochondria are responsible for the acquisition of gemcitabine resistance in pancreatic cancer cell lines.

Pancreatic ductal adenocarcinoma has a particularly poor prognosis as it is often detected at an advanced stage and acquires resistance to chemotherapy early during its course. Stress adaptations by mitochondria, such as metabolic plasticity and regulation of apoptosis, promote cancer cell survival; however, the relationship between mitochondrial dynamics and chemoresistance in pancreatic ductal adenocarcinoma remains unclear. We here established human pancreatic cancer cell lines resistant to gemcitabine from MIA PaCa-2 and Panc1 cells. We compared the cells before and after the acquisition of gemcitabine resistance to investigate the mitochondrial dynamics and protein expression that contribute to this resistance. The mitochondrial number increased in gemcitabine-resistant cells after resistance acquisition, accompanied by a decrease in mitochondrial fission 1 protein, which induces peripheral mitosis, leading to mitophagy. An increase in the number of mitochondria promoted oxidative phosphorylation and increased anti-apoptotic protein expression. Additionally, enhanced oxidative phosphorylation decreased the AMP/ATP ratio and suppressed AMPK activity, resulting in the activation of the HSF1-heat shock protein pathway, which is required for environmental stress tolerance. Synergistic effects observed with BCL2 family or HSF1 inhibition in combination with gemcitabine suggested that the upregulated expression of apoptosis-related proteins caused by the mitochondrial increase may contribute to gemcitabine resistance. The combination of gemcitabine with BCL2 or HSF1 inhibitors may represent a new therapeutic strategy for the treatment of acquired gemcitabine resistance in pancreatic ductal adenocarcinoma.

For safe and fast surgery: Utilization of the SAND balloon catheter for acute cholecystitis.

BACKGROUND: The utility of the SAND balloon catheter in laparoscopic cholecystectomy for acute cholecystitis (AC) remains unclear. METHODS: A retrospective cohort study of patients who underwent emergency cholecystectomy at Shinshu University was performed to evaluate the efficacy of the SAND balloon catheter in cases of AC (SAND balloon utilization: Group S, n = 44; non-utilization: Group non-S, n = 47). RESULTS: The duration of surgery was significantly shorter in Group S than in Group non-S (p = .031). Despite comparable incidences of blood transfusions in the two groups, intraoperative blood loss was significantly less in Group S than in Group non-S (p = .013). The incidence of postoperative intraperitoneal infection tended to be higher in Group non-S (p = .076). Within Group non-S, bile spillage during operation was found in 16 (34.0%) patients. The multivariate analysis revealed that gangrenous AC was the strongest independent risk factor for bile spillage during operation (odds ratio [OR]: 19.1; 95% confidence interval [CI]: 2.84-78.4; p = .002), followed by surgeons with ≤10 years of experience (OR: 11.3; 95% CI: 1.81-70.6; p < .010). CONCLUSIONS: Implementation of the SAND balloon catheter in patients with AC is a safe and efficacious surgical option. This catheter is recommended in cases of gangrenous cholecystitis and for surgeons with limited experience.

Clinical characteristics, prognosis, and surgical outcomes of patients with non-HBV and non-HCV related hepatocellular carcinoma: three-decade observational study.

BACKGROUND: The incidence of non-hepatitis B virus, non-hepatitis C virus hepatocellular carcinoma (non-B non-C-HCC) is increasing worldwide. We assessed the clinical characteristics and surgical outcomes of non-B non-C-HCC, versus hepatitis B (HBV-HCC) and hepatitis C (HCV-HCC). METHODS: Etiologies, fibrosis stages, and survival outcomes were analyzed of 789 consecutive patients who underwent surgery from 1990 to 2020 (HBV-HCC, n = 149; HCV-HCC, n = 424; non-B non-C-HCC, n = 216). RESULTS: The incidence of hypertension and diabetes mellitus was significantly higher in patients with NON-B NON-C-HCC than in those with HBV-HCC and HCV-HCC. Significantly more advanced tumor stages were observed in patients with non-B non-C-HCC; however, better liver function and lower fibrosis stages were observed. Patients with non-B non-C-HCC had significantly worse 5-year overall survival than patients with HBV-HCC; overall survival was comparable between patients with non-B non-C-HCC and HCV-HCC. Patients with HCV-HCC had significantly worse 5-year recurrence-free survival than patients with HBV-HCC and non-B non-C-HCC. In patients with non-B non-C-HCC, overall survival was comparable among three periods (1990-2000, 2001-2010, and 2011-2020) despite significant improvement in patients with HBV-HCC and HCV-HCC. CONCLUSION: The prognosis of non-B non-C-HCC was similar to that of HBV-HCC and HCV-HCC regardless of tumor progression at surgery. Patients with hypertension, diabetes mellitus, and dyslipidemia require careful systematic follow-up and treatment.

De Novo Malignancy After Adult-to-Adult Living Donor Liver Transplantation: A Single-Center Long-Term Experience.

BACKGROUND: The incidence of de novo malignancy (DNM) after liver transplantation (LT) is reported to be 3.1% to 14.4%. It is a known cause of death in long-term recipients. This study aimed to clarify the clinical features and risk factors of DNM. METHODS: Recipients who underwent adult-to-adult living-donor LT (LDLT) and survived for >6 months were investigated. The medical records were retrospectively reviewed. This study was approved by the institutional review board. RESULTS: In total, 180 patients were included. The indications for LDLT were hepatocellular disease (n = 62), metabolic liver disease (n = 50), cholestatic disease (n = 46), acute liver failure (n = 12), and others (n = 10). The median age at LDLT was 48 (18-71) years, and the follow-up period was 15 (0-29) years. De novo malignancy was diagnosed in 24 recipients (28 sites), including the digestive tract (n = 9), genitourinary (n = 5), gynecologic (n = 5), lung (n = 4), hematological (n = 3), and others (n = 2). The median duration from LDLT to DNM was 7 (0-19) years. Four patients were lost to follow-up due to advanced-stage cancer. R0 (curative treatment) for non-hematological DNM was achieved in 19 lesions (95%). The 10- and 20-year DNM incidence rates were 11% and 20%, respectively. The 20-year survival rates of DNM (59.6%) and non-DNM (59.9%) patients were not significantly different. De novo malignancy was significantly higher in patients with primary sclerosing cholangitis than in others (P < .05). CONCLUSIONS: Even in DNM recipients, early detection of malignancy and R0 treatment promises long-term outcomes comparable to those of non-DNM recipients.

Accuracy and limitations of preoperative assessment of longitudinal spread of perihilar cholangiocarcinoma.

OBJECTIVE: Although surgical resection offers the only chance of cure of perihilar cholangiocarcinoma and R1 resection has a poor prognosis, there is no consensus on optimal preoperative assessment of its longitudinal spread. We aimed to establish the optimal means of achieving this goal. METHODS: This was a retrospective, single-center study of 61 patients who had undergone multi-detector row computed tomography, endoscopic retrograde cholangiography, intraductal ultrasonography, and mapping biopsy prior to resection of perihilar cholangiocarcinomas in our institute from January 2010 and December 2021. RESULTS: The most accurate single methods for assessing longitudinal spread were intraductal ultrasonography and mapping biopsy (both 72.1%). A combination of all four assessment methods was accurate in 51 (83.6%) of our patients. Independent risk factors for inaccuracy were Bismuth-Corlette Type IV and high histologic-grade tumors. The R0 resection rate was higher with accurate than inaccurate assessments (90.2% vs. 30.0%, P < 0.001). R0 resection was associated with significantly better relapse-free survival than R1 resection (P = 0.006). However, overall survival did not differ between these groups. CONCLUSION: Preoperative assessment of longitudinal spread of perihilar cholangiocarcinomas by four different modalities is optimal, achieving 83.6% accuracy and a 90.2% R0 resection rate.

Risk factors for postoperative cholangitis after pancreaticoduodenectomy and evaluation of internal stenting on hepaticojejunostomy: A single-center propensity score-based analysis.

BACKGROUND/PURPOSE: This retrospective study aimed to investigate the risk factors for postoperative cholangitis (POC) after pancreaticoduodenectomy (PD) and the efficacy of stenting on hepaticojejunostomy (HJ). METHODS: We investigated 162 patients. Postoperative cholangitis occurring before and after discharge was defined as early-onset POC (E-POC) and late-onset POC (L-POC), respectively. Risk factors for E-POC and L-POC were identified using univariate and multivariate logistic regression analyses. Propensity score matching (PSM) between the stenting group (group S) and the non-stenting group (group NS), and subgroup analysis in patients with risk factors were performed to evaluate the efficacy of stenting on HJ in preventing POC. RESULTS: Body mass index (BMI) ≥ 25 kg/m2 and preoperative non-biliary drainage (BD) were risk factors for E-POC and L-POC, respectively. PSM analysis revealed that E-POC occurrence was significantly higher in group S than in group NS (P = .045). In the preoperative non-BD group (n = 69), E-POC occurrence was significantly higher in group S than in group NS (P = .025). CONCLUSIONS: BMI ≥ 25 kg/m2 and preoperative non-BD status were risk factors for E-POC and L-POC, respectively. Stenting on HJ implants did not prevent POC after PD.

Impact of endothelial nitric oxide synthase activation on accelerated liver regeneration in a rat ALPPS model.

BACKGROUND: Although the associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) induces more rapid liver regeneration than portal vein embolization, the mechanism remains unclear. AIM: To assess the influence of inflammatory cytokines and endothelial nitric oxide synthase (eNOS) activation on liver regeneration in ALPPS. METHODS: The future liver remnant/body weight (FLR/BW) ratio, hepatocyte proliferation, inflammatory cytokine expression, and activation of the Akt-eNOS pathway were evaluated in rat ALPPS and portal vein ligation (PVL) models. Hepatocyte proliferation was assessed based on Ki-67 expression, which was confirmed using immunohistochemistry. The serum concentrations of inflammatory cytokines were measured using enzyme linked immune-solvent assays. The Akt-eNOS pathway was assessed using western blotting. To explore the role of inflammatory cytokines and NO, Kupffer cell inhibitor gadolinium chloride (GdCl3), NOS inhibitor N-nitro-arginine methyl ester (L-NAME), and NO enhancer molsidomine were administered intraperitoneally. RESULTS: The ALPPS group showed significant FLR regeneration (FLR/BW: 1.60% ± 0.08%, P < 0.05) compared with that observed in the PVL group (1.33% ± 0.11%) 48 h after surgery. In the ALPPS group, serum interleukin-6 expression was suppressed using GdCl3 to the same extent as that in the PVL group. However, the FLR/BW ratio and Ki-67 labeling index were significantly higher in the ALPPS group administered GdCl3 (1.72% ± 0.19%, P < 0.05; 22.25% ± 1.30%, P < 0.05) than in the PVL group (1.33% ± 0.11% and 12.78% ± 1.55%, respectively). Phospho-Akt Ser473 and phospho-eNOS Ser1177 levels were enhanced in the ALPPS group compared with those in the PVL group. There was no difference between the ALPPS group treated with L-NAME and the PVL group in the FLR/BW ratio and Ki-67 labeling index. In the PVL group treated with molsidomine, the FLR/BW ratio and Ki-67 labeling index increased to the same level as in the ALPPS group. CONCLUSION: Early induction of inflammatory cytokines may not be pivotal for accelerated FLR regeneration after ALPPS, whereas Akt-eNOS pathway activation may contribute to accelerated regeneration of the FLR.