Treatment strategy for hepatocellular carcinoma recurrence in the transplant era: Focusing on the Japan criteria.

PURPOSE: To clarify the Japan criteria (JC), as proposed in 2019, in order to identify the most appropriate treatment methods for hepatocellular carcinoma (HCC) recurrence and assess the feasibility of pre-living donor liver transplantation (LDLT) downstaging within these criteria. METHODS: The subjects of this study were 169 LDLT patients with HCC recurrence. We performed univariate and multivariate analyses of the factors contributing to HCC recurrence after LDLT and clarified the post-transplant outcomes of pre-LDLT downstaging. RESULTS: Univariate and multivariate analysis identified beyond the JC (p = 0.0018) and a neutrophil-to-lymphocyte ratio > 2.01 (p = 0.029) as independent risk factors. Patients who met the JC had significantly higher recurrence-free and overall survival rates after LDLT (p < 0.0001) than those who did not (p = 0.0002). The post-transplant outcomes of patients within the JC after downstaging were significantly better than those of patients beyond the JC (p = 0.034) and equivalent to those within the JC without downstaging. CONCLUSION: Even for HCC recurrence, the JC could play an important role in deciding on the best treatment strategy, and downstaging within the JC had good post-transplant outcomes.

Curative surgery for multiple hepatocellular carcinomas after lenvatinib plus transarterial chemoembolization: a case report.

Surgical therapy following lenvatinib (LEN) plus transarterial chemoembolization (TACE) is a useful therapeutic option for intermediate-stage hepatocellular carcinoma (HCC). A 66-year-old man with a history of hepatitis C was detected four masses in the caudate lobe and segment 6/7 of the liver, with a maximum lesion diameter of 14 cm by computed tomography. The patient was diagnosed with intermediate-stage HCC and received LEN plus TACE. After resuming LEN for 8 weeks, computed tomography showed weakened stained areas of the tumors, and no new lesions. Thus, the patient was evaluated as having a partial response in the modified Response Evaluation Criteria in Solid Tumors. The patient underwent hepatic caudate lobectomy, partial hepatectomy of S6/7, and S6 microwave coagulation therapy for radical resection. The patient is currently alive and recurrence-free at 12 months postoperatively. In patients with multiple HCC lesions, hepatic resection combined with local therapy might be an effective treatment option.

Effect of duration of adjuvant chemotherapy with S-1 (6 versus 12 months) for resected pancreatic cancer: the multicenter clinical randomized phase II postoperative adjuvant chemotherapy S-1 (PACS-1) trial.

BACKGROUND: Six-month adjuvant chemotherapy with S-1 is standard care for resected pancreatic cancer in Japan; however, the optimal duration has not been established. We aimed to evaluate the impact of duration of adjuvant chemotherapy with S-1. METHODS: We performed a multicenter, randomized, open-label, phase II study. Patients with histologically proven invasive pancreatic ductal carcinoma, pathological stage I-III, and no local residual or microscopic residual tumor were eligible. Patients were randomized 1:1 to receive 6- or 12-month adjuvant chemotherapy with S-1. The primary endpoint was 2-year overall survival (OS). Secondary endpoints were disease-free survival (DFS) and feasibility. RESULTS: A total of 170 patients were randomized (85 per group); the full analysis set was 82 in both groups. Completion rates were 64.7% (6-month group) and 44.0% (12-month group). Two-year OS was 71.5% (6-month group) and 65.4% (12-month group) (hazard ratio (HR): 1.143; 80% confidence interval CI 0.841-1.553; P = 0.5758). Two-year DFS was 46.4% (6-month group) and 44.9% (12-month group) (HR: 1.069; 95% CI 0.727-1.572; P = 0.6448). In patients who completed the regimen, 2-year DFS was 56.5% (6-month group) and 75.0% (12-month group) (HR: 0.586; 95% CI 0.310-1.105; P = 0.0944). Frequent (≥ 5%) grade ≥ 3 adverse events comprised anorexia (10.5% in the 6-month group) and diarrhea (5.3% vs. 5.1%; 6- vs. 12-month group, respectively). CONCLUSIONS: In patients with resected pancreatic cancer, 12-month adjuvant chemotherapy with S-1 was not superior to 6-month therapy regarding OS and DFS.

Surgical treatment of hepatocellular carcinoma after Fontan operation: three case reports and review of the literature.

We herein describe three patients with Fontan-associated liver disease who developed hepatocellular carcinoma (HCC). The first patient was a 28-year-old woman who had undergone the Fontan operation (FO) at the age of 4 years. She was diagnosed with HCC (cT4aN0M0, Stage IVA, UICC 8th edition), for which she underwent extended posterior right sectionectomy and partial hepatectomy of S2. She developed recurrence of peritoneal dissemination after 12 months, and she was alive 18 months after surgery. The second patient was a 43-year-old man who had undergone the FO at the age of 3 years. He was diagnosed with HCC (cT2N0M0, Stage II), for which he underwent laparoscopic-assisted partial hepatectomy of S3. He remained free from recurrent HCC for 17 months. The third patient was a 21-year-old woman who had undergone the FO at the age of 3 years. She was diagnosed with HCC (cT3N0M0, Stage III), for which she underwent laparoscopic-assisted partial hepatectomy of S2 and S4. She remained free from recurrent HCC for 30 months. We reviewed 18 surgical cases of HCC arising from Fontan-associated liver disease, including our 3 cases, and found that a high preoperative alpha-fetoprotein concentration might be a predictor of HCC recurrence.

Validation of quantitative prognostic prediction using ADV score for resection of hepatocellular carcinoma: A Korea-Japan collaborative study with 9200 patients.

BACKGROUND: A score derived from the concentrations of α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) and tumor volume (TV), called ADV score, has been shown to be prognostic of hepatocellular carcinoma (HCC) recurrence following hepatic resection (HR) or liver transplantation. METHODS: This multicenter, multinational validation study included 9200 patients who underwent HR from 2010 to 2017 at 10 Korean and 73 Japanese centers, and were followed up until 2020. RESULTS: AFP, DCP, and TV showed weak correlations (ρ ≤ .463, r ≤ .189, p < .001). Disease-free survival (DFS), overall survival (OS), and post-recurrence survival rates were dependent on 1.0 log and 2.0 log intervals of ADV scores (p < .001). Receiver operating characteristic (ROC) curve analysis showed that ADV score cutoffs of 5.0 log for DFS and OS yielded the areas under the curve ≥ .577, with both being significantly prognostic of tumor recurrence and patient mortality at 3 years. ADV score cutoffs of ADV 4.0 log and 8.0 log, derived through K-adaptive partitioning method, showed higher prognostic contrasts in DFS and OS. ROC curve analysis showed that an ADV score cutoff of 4.2 log was suggestive of microvascular invasion, with both microvascular invasion and an ADV score cutoff of 4.2 log showing similar DFS rates. CONCLUSIONS: This international validation study demonstrated that ADV score is an integrated surrogate biomarker for post-resection prognosis of HCC. Prognostic prediction using ADV score can provide reliable information that can assist in planning treatment of patients with different stages of HCC and guide individualized post-resection follow-up based on the relative risk of HCC recurrence.

The hemoglobin, albumin, lymphocyte, and platelet score is a prognostic factor for Child-Pugh A patients undergoing curative hepatic resection for single and small hepatocellular carcinoma.

AIM: The hemoglobin, albumin, lymphocyte, and platelet (HALP) score reflects the immune system and the nutritional status of patients, and prognosis in various cancers. However, the HALP score in hepatocellular carcinoma has not been reported. METHODS: Data were analyzed retrospectively from Child-Pugh A patients undergoing hepatic resection for single hepatocellular carcinoma ≤5 cm. For cross-validation, patients were divided into the training (332 patients) and validation cohort (210 patients). In the training cohort, we divided patients into two groups by appropriate cut-off value of the HALP score, and univariable and multivariable analyses were conducted for disease-free and overall survival (OS) between two groups. In the validation cohort, we examined OS by Kaplan-Meier analysis in the same cut-off value of the HALP score in the training cohort. RESULTS: The HALP-low group was significantly older (p = 0.0003), had fewer hepatitis B surface antigen-positive patients (p = 0.0369), higher prothrombin time (p = 0.0141), lower fibrosis-4 index (p = 0.0206), bigger maximum tumor size (p = 0.0196), and less histological liver fibrosis (p = 0.0077). Multivariate analysis showed that the independent prognostic factors for disease-free survival were fibrosis-4 index ≥2.67 (p = 0.0008), simple nodular type with extranodular growth or confluent multinodular type (p = 0.0221), and intrahepatic metastasis (p = 0.0233), and that for OS were fibrosis-4 index ≥2.67 (p = 0.0020), HALP ≤45.6 (p = 0.0228), and poor differentiation (p = 0.0305). In the validation cohort, Kaplan-Meier analysis revealed the trend toward significantly impaired OS (p = 0.0220) in the HALP-low group. CONCLUSION: We showed that a low HALP score is the independent prognostic factor for Child-Pugh A patients undergoing curative hepatic resection for single and small hepatocellular carcinoma.

Prognostic significance for recurrence of fibroblast growth factor receptor 2 in intrahepatic cholangiocarcinoma patients undergoing curative hepatic resection.

AIMS: The fibroblast growth factor receptor 2 (FGFR2) fusion gene is frequently found as a genetic abnormality in the FGFR pathway in patients with intrahepatic cholangiocarcinoma (ICC). The FGFR fusion protein, produced from the FGFR fusion gene, is thought to cause tumor cell growth. To date, there have been few reports on the relationship between pathologic FGFR2 expression and prognosis in patients who have undergone hepatectomy for ICC, and on the relationship between FGFR2 and tumor-infiltrating lymphocytes (TILs). METHODS AND RESULTS: We enrolled 92 patients who underwent hepatectomy for ICC and performed immunohistochemical staining for FGFR2 and cluster of differentiation 8, and hematoxylin and eosin staining for evaluating TILSs. The relationships between the FGFR2 and clinicopathological characteristics and outcomes were analyzed, and patients were classified into positive (n = 18) and negative (n = 74) FGFR2 groups. The FGFR2-positive group contained more men (p < 0.0001) and had lower serum albumin (p = 0.0355) and higher carcinoembryonic antigen (p = 0.0099). Furthermore, multivariable analyses revealed that the FGFR2-positive group had worse disease-free survival (DFS) (p = 0.0002). Multivariate analysis showed that the independent prognostic factors for DFS were maximum tumor size (≥5 cm) (p = 0.0011), tumor localization (perihilar type) (p = 0.0180), and FGFR2 positivity (p = 0.0029). There was no significant difference in TILs count between the two groups. CONCLUSION: We showed that FGFR2 high expression was an independent prognostic factor for recurrence of resected ICC.

Impact of a 7.5-Fr Pancreatic Stent for Preventing Pancreatic Fistula after Pancreaticoduodenectomy.

INTRODUCTION: Pancreatic duct stents are widely used to reduce the incidence of postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD); however, small stents may cause adverse effects, such as occlusion. Recently, we have tried placing a 7.5-Fr pancreatic duct stent to achieve more effective exocrine output from the pancreas; however, the association between pancreatic duct stent size and POPF remains unknown. METHODS: Sixty-five patients with soft pancreatic texture who underwent PD were retrospectively analyzed. After dividing the pancreas, a pancreatic duct stent (stent size 4.0 in 29 patients, 5.0 in 18, and 7.5 Fr in 18) was placed in the main pancreatic duct. RESULTS: Twenty-five of 65 patients with soft pancreatic texture (38.5%) developed POPF. POPF became less frequent as the pancreatic duct stent size increased (p = 0.003). The factors associated with POPF development were a 7.5-Fr pancreatic duct stent (p = 0.005), 5.0-Fr pancreatic duct stent (p = 0.031), and male sex (p = 0.008). Pancreatic duct stent size and pancreatic duct diameter did not differ between the POPF and non-POPF groups. DISCUSSION/CONCLUSIONS: In patients with a soft pancreas, the placement of a 7.5-Fr pancreatic duct stent may reduce the incidence of POPF.

Efficacy of neoadjuvant chemotherapy in patients with high-risk resectable colorectal liver metastases.

BACKGROUND: The role of preoperative neoadjuvant chemotherapy (NAC) in patients with resectable colorectal liver metastases (CRLM) remains undetermined. This study aimed to assess the efficacy of NAC in patients with resectable CRLM, especially in high-risk subgroups for recurrence, with special reference to synchronicity and the CRLM grade in the Japanese classification system. METHODS: A retrospective analysis of a multi-institutional cohort who was diagnosed with resectable CRLM was performed. CRLM was classified into three grades (A, B, and C) according to the combination of H stage (H1: ≤ 4 lesions and ≤ 5 cm, H2: ≥ 5 lesions or > 5 cm, H3: ≥ 5 lesions and > 5 cm), nodal status of the primary tumor (pN0/1: ≤ 3 metastases, pN2: ≥ 4 metastases), and the presence of resectable extrahepatic metastases. RESULTS: Among 222 patients with resectable CRLM, 97 (43.7%) had synchronous CRLM. The surgical failure-free survival (SF-FS) of patients with synchronous CRLM (without NAC) was significantly worse than that of patients with metachronous CRLM (P = 0.0264). The SF-FS of patients with Grade B/C was also significantly worse than that of Grade A (P = 0.0058). Among the 53 patients with synchronous and Grade B/C CRLM, 31 were assigned to NAC, and all of them underwent liver surgery. In this high-risk subgroup, the SF-FS and OS in the NAC group were significantly better than those in the upfront surgery group (P < 0.0001 and P = 0.0004, respectively). CONCLUSIONS: Patients with synchronous and Grade B/C CRLM could be good candidates for indication of NAC.

Laparoscopic treatment of median arcuate ligament syndrome without ganglionectomy of the celiac plexus in the hybrid operating room: Report of a case.

INTRODUCTION: Median arcuate ligament syndrome (MALS) is a rare condition in which the median arcuate ligament (MAL) causes compression of the celiac artery (CA) and plexus. Although 13-50 % of healthy population exhibit radiologic evidence of the CA compression, the majority remains asymptomatic. With or without symptoms, MALS have a risk of developing collateral circulation that leads to pancreaticoduodenal artery (PDA) aneurysms that have high risk of rupture. The treatment of MALS is the surgical release of the MAL. However, the necessity of ganglionectomy of the celiac plexus is still unclear. PRESENTATION OF CASE: A 60-year-old man with a ruptured PDA aneurysm caused by MALS was admitted to our hospital for an emergency. After treatment for the ruptured PDA aneurysm by transcatheter arterial coil embolization, he underwent elective laparoscopic MAL release in the hybrid operation room to check blood flow of the CA intraoperatively. The angiography of the CA immediately after MAL release without ganglionectomy of the celiac plexus showed the antegrade blood flow to the proper hepatic artery instead of the retrograde flow via the pancreaticoduodenal arcade. The postoperative course was uneventful and the follow-up computed tomography revealed no residual CA stenosis. DISCUSSION: Unlike symptomatic MALS, it might be enough to just release the MAL without ganglionectomy of the celiac plexus for asymptomatic MALS, especially that with the treated PDA aneurysm. CONCLUSION: Laparoscopic treatment of MALS in hybrid operating room could allow for adequate MAL release without ganglionectomy of the celiac plexus using the intraoperative angiography of the CA.

Effects of Early Physical Therapist-supervised Walking on Clinical Outcomes after Liver Resection: Propensity Score Matching Analysis.

OBJECTIVE: The study aimed to demonstrate the significance of early postoperative physical therapy interventions on clinical outcomes by determining the influence of the distance walked under the supervision of a physical therapist in the early postoperative period after liver cancer. METHODS: All consecutive patients who underwent surgery for liver cancer between April 2018 and March 2020 were eligible for enrollment in the study. The total walking distance during physical therapy till the third postoperative day was examined. The clinical outcomes comprised duration of postoperative hospital stay, time to independent walking, and occurrence of postoperative complications. For data analysis, the patients were divided into two groups: those who walked more than the median total distance (the long-distance group) and those who walked less than the median distance (the short-distance group). We used propensity score matching to match the background characteristics between the groups. RESULTS: Of the 65 patients who were eligible, 14 patients were included in the two groups each, after matching. The long-distance walking group had a significantly shorter hospital stay (9.0 days vs. 11.0 days, p=0.008) and a shorter time to independent walking (3.5 days vs. 7.5 days, p=0.019) than the short-distance walking group. There were no significant differences in postoperative complications between the two groups (7.1% vs. 42.8%, p=0.08). CONCLUSION: In the early postoperative period after liver cancer surgery, increasing the walking distance under the supervision of a physical therapist is important for improving clinical outcomes. Further prospective studies are needed to confirm the findings of this study.

Risk Factors for and Outcomes of Intraoperative Blood Loss in Liver Resection for Hepatocellular Tumors.

Intraoperative blood loss (IBL) during liver resection is a predictor of morbidity, mortality, and tumor recurrence after hepatectomy; however, there have been few reports on patient factors associated with increased IBL. We enrolled consecutive patients who underwent liver resection for primary liver malignancies, and evaluated the predictors of IBL using a data set in which factors that might influence IBL, such as surgical devices, methods and anesthetic technique, were all standardized. We studied 244 patients. A multivariate analysis revealed that higher IBL was an independent risk factor for post-hepatectomy liver failure grade ≥B and overall survival. Multiple linear regression analyses showed serum creatinine, clinically significant portal hypertension (CSPH), tumor size, and major hepatectomy were all significant predictors of IBL. In conclusion, higher IBL was significantly associated with increased morbidity and mortality in patients with primary HCC who underwent liver resection. The risk of IBL was related to several factors including tumor size, serum creatinine, CSPH, and major hepatectomy.

Hepatic resection for recurrent hepatocellular carcinoma during pregnancy: a case report.

BACKGROUND: Hepatocellular carcinoma (HCC) during pregnancy is extremely rare. Treatment strategies for cancers detected during pregnancy have been controversial. We herein report a case of recurrent HCC detected at 20 weeks of pregnancy, which subsequently prompted hepatic resection after abortion. CASE PRESENTATION: A 36-year-old woman underwent laparoscopic partial hepatectomy for HCC (20 mm in diameter) in segment 5 of the liver during follow-up after being determined as a hepatitis B virus carrier two and a half years ago. Post-surgery follow-up abdominal ultrasonography revealed a 36-mm tumor in segment 7 of the liver. Abdominal contrast-enhanced computed tomography revealed a well-enhanced tumor with a 40-mm diameter in segment 7 adjacent to the inferior vena cava and right hepatic vein, suggesting HCC recurrence. Laboratory data revealed total bilirubin (0.4 mg/dL), aspartate aminotransferase (28 IU/L), alanine aminotransferase (30 IU/L), glutamyltransferase (16 IU/L), prothrombin time (115.3%), and indocyanine green retention rate at 15 min (7.0%). α-Fetoprotein (AFP) (12,371.5 ng/mL; normal range < 10 ng/mL) and PIVKA-II (208 mAU/mL; normal range < 40 mAU/mL) were both significantly elevated. After discussions with a cancer board consisting of experts from the departments of gastroenterology, obstetrics and gynecology, and surgery, as well as obtaining appropriate informed consent from the patient and her family, we decided to perform a hepatic resection after abortion. Subsequently, abortion surgery was performed at 21 weeks and 2 days of pregnancy. After 6 days, subsegmentectomy of liver segment 7 was performed under general and epidural anesthesia, with a pathological diagnosis which was moderately differentiated HCC being established. Given the good postoperative course, without particular complications, the patient was subsequently discharged 10 days after the operation. Approximately 2 years after the surgery, the patient remains alive without recurrence, while both AFP and PIVKA-II were within normal limits. CONCLUSIONS: Treatment strategies for HCC detected during pregnancy remain controversial. As such, decisions should be made based on HCC growth and fetal maturity after thorough multidisciplinary team discussions and obtaining appropriate informed consent from the patient and her family.

The Effect of Prone Positioning as Postoperative Physiotherapy to Prevent Atelectasis After Hepatectomy.

BACKGROUND: The incidences of postoperative pulmonary complications (PPCs) such as atelectasis, pneumonia and pleural effusion after major surgery range from <1 to 23%. Atelectasis after abdominal surgery increases the duration of hospitalization and short-term mortality rate, but there are few reports about atelectasis after hepatectomy. The effectiveness of prone position drainage as physiotherapy has been reported, but it remains unclarified whether prone positioning prevents atelectasis after hepatectomy. This study aimed to evaluate the effect of the prone position on the incidence of atelectasis after hepatectomy. METHODS: We retrospectively analyzed the incidence of PPCs after hepatectomy at a single center. Patients were divided into two cohorts. The earlier cohort (n = 165) underwent hepatectomy between January 2016 and March 2018 and was analyzed to identify the risk factors for atelectasis and short-term outcomes; the later cohort (n = 51) underwent hepatectomy between April 2018 and March 2019 and underwent prone position drainage in addition to regular mobilization postoperatively. The incidences of PPCs were compared between the two cohorts. RESULTS: Independent risk factors for atelectasis were anesthetic duration (P = 0.016), operation time (P = 0.046) and open surgery (P = 0.011). The incidence of atelectasis was significantly lower in the later cohort (9.8%) than the earlier cohort (34.5%, P < 0.001). Moreover, the later cohort had a significantly shorter duration of oxygen support (P < 0.001) and postoperative hospitalization (P < 0.001). After propensity score-matching, the incidence of atelectasis remained significantly lower in the later cohort (P = 0.027). CONCLUSION: Prone position drainage may decrease the incidence of atelectasis after hepatectomy and improve the short-term outcomes.

Mixed adenoneuroendocrine carcinoma of the distal bile duct: a case report.

BACKGROUND: Mixed adenoneuroendocrine carcinoma (MANEC) of the common bile duct (CBD) is very rare, with only 10 reported cases. Here, we report a case of MANEC of the distal bile duct (DBD) that was surgically resected under a diagnosis of cholangiocarcinoma (CCA). CASE PRESENTATION: A 60-year-old male had epigastric pain and was admitted to our hospital for the treatment of a suspected CBD stone. Upon admission, laboratory findings revealed elevated hepatobiliary enzymes including serum aspartate aminotransferase, serum alanine aminotransferase, serum glutamyltransferase, and serum alkaline phosphatase. Both carcinoembryonic antigen and carbohydrate antigen 19-9 were negative. Computed tomography (CT) showed dilation of the CBD. Endoscopic retrograde cholangiopancreatography (ERCP) showed circumferential stenosis and a 5-mm elevated lesion in the DBD. Brush cytology showed atypical ductal cells, indicating adenocarcinoma (AC) of the DBD. Under a diagnosis of CCA of the DBD, a subtotal stomach-preserving pancreaticoduodenectomy was performed. Neither peritoneal dissemination nor lymph node metastasis was found. Microscopically, the lesion was seen to be composed of predominantly well-differentiated tubular AC in the superficial layer of the tumor, admixed with neuroendocrine carcinoma (NEC) in the deeper portion, indicating a diagnosis of MANEC of the DBD. After immunohistochemical staining, NEC components were positive for synaptophysin and CD56 and were for SSTR2, SSTR5, and mammalian target of rapamycin (mTOR). Three months postsurgery, postoperative adjuvant chemotherapy with S-1 was started. More than 3 years postsurgery, he is alive without recurrence. CONCLUSIONS: MANEC is highly malignant, progresses rapidly, and has a poor prognosis. Preoperative diagnosis is difficult; therefore, identifying NEC components by immunohistochemical staining using resected specimens is important.

Elevation of Mac-2 binding protein glycosylation isomer after hepatectomy is associated with post-hepatectomy liver failure, total Pringle time, and renal dysfunction.

BACKGROUND: Mac-2 binding protein glycosylation isomer (M2BPGi) is a novel serum glycomarker used to assess liver fibrosis. However, it has been reported that M2BPGi is likely to reflect other factors not limited to liver fibrosis. METHODS: We retrospectively analyzed 79 patients with liver tumors who underwent liver resection. M2BPGi was measured within 1 week before operation and almost 1 month after operation. We introduced a value termed the "ΔM2BPGi ratio" (=M2BPGiafter operation/M2BPGibefore operation), and analyzed factors that influenced the ΔM2BPGi ratio. RESULTS: The median value of the ΔM2BPGi ratio was 1.28 (range, 0.36-5.68). In 64 patients (81.0%), the cutoff index values of M2BPGi were elevated approximately 1 month after operation, especially in patients who experienced post-hepatectomy liver failure (PHLF). Multiple linear regression showed total Pringle time, PHLF grade ≥B, and preoperative value of creatinine were significant predictors of the ΔM2BPGi ratio. The mean values of the ΔM2BPGi ratio were 1.37 ± 0.07, 1.52 ± 0.22, and 2.94 ± 0.30 for PHLF grade 0, grade A, and grade B, respectively, resulting in statistically significant differences by the Kruskal-Wallis test (P = 0.022). CONCLUSIONS: Total Pringle time, PHLF grade ≥B, and preoperative creatinine significantly influenced the elevation of M2BPGi almost 1 month after liver resection. This study strongly affirms the previous suggestion that M2BPGi is likely to reflect other factors not limited to liver fibrosis.

Evaluation of Drain Amylase Level after Pancreaticoduodenectomy with Special Reference to Delayed Pancreatic Fistula.

Postoperative pancreatic fistula (PF) is a relatively frequent and occasionally fatal complication of pancreatoduodenectomy (PD). Several risk factors for PF have been reported, including high drain amylase level (D-AMY). Among the 140 consecutive patients who underwent PD, we analyzed 110 cases with D-AMY measurements over time after PD. According to the D-AMY change, we divided patients into five patterns and defined delayed PF cases. We analyzed clinical characteristics, including serum amylase and D-AMY, and examined the correlation between the period of drain insertion and PF grade. In 15 delayed PF cases, 12 cases were grade B or C, pancreatic cancer was less frequent, pancreatic ducts were smaller, and soft pancreas texture was more commonly observed. The D-AMY on postoperative day (POD) 1 was higher in cases of delayed PF compared with non-PF cases (P < 0.0001). In 28 cases with drain removal before POD 7, grade B or C PF was not observed afterward. The average D-AMY on POD 1 in cases with drain removal before POD 1 was significantly lower than in delayed PF cases. Although further studies are required to determine the most appropriate timing of drain removal, it is thought that intra-abdominal drains should be removed within seven days of PD in cases without signs of PF. On the other hand, delayed PF should be considered in cases of soft pancreas texture and/or high D-AMY on POD 1, even if D-AMY levels are low on POD 3 or decreasing on POD 5.

Myeloid-derived suppressor cells increase and inhibit donor-reactive T cell responses to graft intestinal epithelium in intestinal transplant patients.

Recent advances in immunosuppressive regimens have decreased acute cellular rejection (ACR) rates and improved intestinal and multivisceral transplant (ITx) recipient survival. We investigated the role of myeloid-derived suppressor cells (MDSCs) in ITx. We identified MDSCs as CD33+ CD11b+ lineage(CD3/CD56/CD19)- HLA-DR-/low cells with 3 subsets, CD14- CD15- (e-MDSCs), CD14+ CD15- (M-MDSCs), and CD14- CD15+ (PMN-MDSCs), in peripheral blood mononuclear cells (PBMCs) and mononuclear cells in the grafted intestinal mucosa. Total MDSC numbers increased in PBMCs after ITx; among MDSC subsets, M-MDSC numbers were maintained at a high level after 2 months post ITx. The MDSC numbers decreased in ITx recipients with ACR. MDSC numbers were positively correlated with serum interleukin (IL)-6 levels and the glucocorticoid administration index. IL-6 and methylprednisolone enhanced the differentiation of bone marrow cells to MDSCs in vitro. M-MDSCs and e-MDSCs expressed CCR1, -2, and -3; e-MDSCs and PMN-MDSCs expressed CXCR2; and intestinal grafts expressed the corresponding chemokine ligands after ITx. Of note, the percentage of MDSCs among intestinal mucosal CD45+ cells increased after ITx. A novel in vitro assay demonstrated that MDSCs suppressed donor-reactive T cell-mediated destruction of donor intestinal epithelial organoids. Taken together, our results suggest that MDSCs accumulate in the recipient PBMCs and the grafted intestinal mucosa in ITx, and may regulate ACR.