Critical Role of Preoperative Hyperglycemia in Association with GFAT-1 Expression in Resected Pancreatic Cancer.

BACKGROUND: Hyperglycemia is involved in malignant transformation of pancreatic cancer via the hexosamine biosynthetic pathway (HBP). However, few studies have verified this mechanism based on clinical data. This study investigated the complementary effects of hyperglycemia and HBP on pancreatic cancer prognosis using detailed clinical data. METHODS: The study analyzed data of 477 patients with pancreatic cancer who underwent pancreatectomy between 2006 and 2020. The patients were divided into normoglycemia and hyperglycemia groups based on their HbA1c levels. Immunostaining for glutamine fructose-6-phosphate transaminase-1 (GFAT-1), the rate-limiting enzyme in HBP, CD4, CD8, and Foxp3, was performed to evaluate the association between survival outcomes, HBP, and local tumor immunity. RESULTS: Overall survival (OS) was significantly poorer in the hyperglycemia group than in the normoglycemia group (mean survival time [MST]: 35.0 vs. 47.9 months; p = 0.007). The patients in the hyperglycemia group with high GFAT-1 expression had significantly poorer OS than those with low GFAT-1 expression (MST, 49.0 vs. 27.6 months; p < 0.001). However, the prognosis did not differ significantly between the patients with high and low GFAT-1 expression in the normoglycemia group. In addition, the patients with hyperglycemia and high GFAT-1 expression had fewer CD4+ (p = 0.015) and CD8+ (p = 0.017) T cells and a lower CD8+/Foxp3+ ratio (p = 0.032) than those with hyperglycemia and low GFAT-1 expression. CONCLUSIONS: The patients with hyperglycemia and high GFAT-1 expression levels had an extremely poor prognosis. Furthermore, the tumors in these patients were characterized as immunologically cold tumors.

Feasibility and efficacy of cell-free and concentrate ascites reinfusion therapy (CART) for advanced pancreatic cancer patients with massive malignant ascites.

BACKGROUND: The management of malignant ascites is critical for treating patients with advanced pancreatic cancer. The purpose of this study was to assess the safety of cell-free and concentrated ascites reinfusion therapy (CART) and its impact on the prognosis of patients with advanced pancreatic cancer who have massive malignant ascites. METHODS: This study analyzed 47 procedures in 29 patients who underwent CART for ascites caused by pancreatic cancer between 2015 and 2022. Among them, 7 patients who received chemotherapy following CART were classified as the chemotherapy group, while 22 patients without chemotherapy after CART were classified as the palliative care group. RESULTS: Among the 47 procedures, adverse events (AEs) were observed in 9 procedures (19 %). Grade 2 adverse events were observed only in one procedure, manifested as fever. There were no grade 3 or 4 AEs, nor were there any treatment-related deaths. The median survival time was 4.0 months in the chemotherapy group and 0.7 months in the palliative care group (p = 0.004). The albumin level in the chemotherapy group was significantly higher than that in the palliative care group. CONCLUSION: CART is feasible and might be the optimal option to enable prolonged use of chemotherapy to improve the prognosis for late-stage pancreatic cancer patients.

Clinical impact of carbonic anhydrase 9 expression on neoadjuvant chemoradiotherapy in pancreatic ductal adenocarcinoma.

BACKGROUND: PDAC cells upregulate carbonic anhydrase 9 (CA9) expression in order to survive in hypoxic tumor environments, which plays a key role in tumor progression. However, the relationship between CA9 expression and preoperative treatment has not been clarified. We evaluated the clinical impact of CA9 expression on the efficacy of neoadjuvant chemoradiotherapy (NACRT) in pancreatic ductal adenocarcinoma (PDAC). METHODS: We investigated CA9 expression in 273 surgical specimens and 20 serum samples obtained from patients with PDAC and evaluated their clinical outcomes. We analyzed the function of CA9 using human pancreatic cancer cell lines. RESULTS: CA9 was positively expressed in 36.2 % of patients who underwent NACRT, which was significantly lower than those who underwent upfront surgery (US) (58.9 %, p < 0.001). Interestingly, patients who were CA9-positive in the US group had a significantly poorer prognosis than that of those in the NACRT group (median survival time [MST], 21.5 months vs. 49.2 months, p < 0.001), while there was no significant difference between patients who were CA9-negative in the US and NACRT groups (MST, 45.8 months vs. 46.3 months, p = 0.357). Moreover, serum CA9 levels tended to correlate positively with CA9 expression in cancer tissues. In-vitro experiments demonstrated that CA9 expression was reduced after treatments with radiation and chemoradiation therapy (RT/CRT), and that CA9 knockdown suppressed the impact of RT/CRT on cancer cell proliferation. CONCLUSIONS: CA9 may act as a target molecule for RT/CRT, highlighting its clinical importance as a valuable biomarker for more stringent indications for NACRT.

Significance of multiple tumor markers measurements in conversion surgery for unresectable locally advanced pancreatic cancer.

BACKGROUND: This study aimed to evaluate the significance of multiple tumor markers (TMs) measurements in determining the indications for conversion surgery (CS) in the management of unresectable locally advanced pancreatic cancer (UR-LAPC). METHODS: A total of 103 patients with UR-LAPC, treated between 2008 and June 2021, were enrolled in this study. Three TMs, including carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), and Duke pancreatic monoclonal antigen type 2 (DUPAN-2), were measured. RESULTS: Twenty-five patients (24%) underwent CS. The median preoperative treatment period was 9.5 months. The median survival time (MST) from the initial treatment for patients with CS was significantly longer than that for patients without surgery (34.6 vs. 18.9 months, P < 0.001). The number of elevated TMs before CS was one in five patients and two in five patients, while 15 patients had normal levels of all three TMs. Notably, the MST from the initial treatment for patients with all three preoperative normal TMs levels was favorable for 70.5 months. In contrast, patients with one or two preoperatively elevated TMs levels had a significantly worse prognosis (25.4 and 21.0 months, respectively, P < 0.001). Furthermore, the relapse-free survival of patients with three preoperative normal TMs levels was significantly longer than those with one or two elevated TMs levels (21.9 vs. 11.3 or 3.0 months, respectively, P < 0.001). Non-normal values of all TMs before CS were identified as independent poor prognostic factors. CONCLUSIONS: Simultaneous measurement and assessment of the three TMs levels may help determine the surgical indications for UR-LAPC after systemic anticancer treatment.

Combination of carbohydrate antigen 19-9 level and tumor size after neoadjuvant chemoradiation therapy may predict early recurrence of resectable pancreatic ductal adenocarcinoma.

BACKGROUND: Although the overall survival rate of patients with resectable pancreatic cancer has gradually improved, some patients relapse early and have a poor prognosis. This study aimed to identify the preoperative risk factors for early recurrence after neoadjuvant chemoradiotherapy in patients with resectable pancreatic cancer. METHODS: This study analyzed patients who underwent pancreatectomy after receiving neoadjuvant chemoradiotherapy for resectable pancreatic cancer between January 2009 and June 2021 and excluded those with borderline resectable and unresectable pancreatic cancers. Early recurrence was defined as recurrence within 6 months after surgery. RESULTS: This study included 203 patients, of whom 22 experienced early recurrence. The median survival time of patients with early recurrence was 18.3 months, which was significantly worse than that of patients with late recurrence (44.0 months, p < 0.001) or no recurrence (not reached, p < 0.001). Logistic regression analysis revealed that a carbohydrate antigen 19-9 level of >100 units/mL and a T status of ≥T2 after neoadjuvant chemoradiotherapy were independent predictive risk factors for early recurrence. The median recurrence-free survival time of patients with two risk factors was 9.7 months and significantly worse than that of those with either risk factors (20.5 months, p = 0.024) and those with no risk factor (26.2 months, p < 0.001). CONCLUSIONS: A combination of a high-level carbohydrate antigen 19-9 and a T status of ≥T2 after neoadjuvant chemoradiotherapy are predictors of early recurrence and may be helpful for selecting patients who require a stronger preoperative treatment.

Impact of the Prolonged Intermittent Pringle Maneuver on Post-Hepatectomy Liver Failure: Comparison of Open and Laparoscopic Approaches.

BACKGROUND: The influence of prolonged intermittent Pringle maneuver (IPM) on post-hepatectomy liver failure (PHLF) remains unclear. We evaluated the impact of the prolonged IPM on PHLF in patients undergoing open and laparoscopic hepatectomy. METHODS: We retrospectively included 546 patients who underwent hepatectomy using IPM. The patients were divided into open (n = 294) and laparoscopic (n = 252) groups. Odds ratios for PHLF occurrence were estimated in each group according to cumulative Pringle time (CPT). The cut-off value was set at CPT of 120 min. Risk factors for PHLF were evaluated in the open and laparoscopic groups. Additionally, we analyzed the post-operative outcomes in the open and laparoscopic groups with CPT ≥ 120 min and performed propensity score matching analysis based on PFLF-associated factors. RESULTS: In the open group, the risk of PHLF increased as CPT increased, particularly after 120 min. However, in the laparoscopic group, PHLF did not occur at less than 60 min, and the risk of PHLF was not significantly different at more than 60 min. Multivariate analysis identified CPT ≥ 120 min as an independent risk factor for PHLF in the open group (p < 0.001), but not in the laparoscopic group. Propensity score matching analysis showed that the PHLF rate was significantly lower in the laparoscopic group with CPT ≥ 120 min (p = 0.027). The post-operative transaminase levels were significantly lower in the laparoscopic group with CPT ≥ 120 min. CONCLUSIONS: Laparoscopic hepatectomy may cause less PHLF with prolonged IPM compared with open hepatectomy.

Detailed analysis of recurrent sites after wedge resection for primary hepatocellular carcinoma considering the potential usefulness of anatomic resection: a retrospective cohort study.

PURPOSE: We investigated the detailed recurrent sites after wedge liver resection for primary hepatocellular carcinoma (HCC). METHODS: We retrospectively reviewed 278 patients with primary HCC who underwent curative liver resection between 2000 and 2016. Recurrent sites were divided into four groups: around the initial HCC (segmental recurrence), within the same section as the primary HCC (sectional recurrence), within the same lobe as the primary HCC (lobar recurrence), and contralateral or extrahepatic recurrence (extra recurrence). RESULTS: Recurrence was observed in 101 of 147 patients who underwent wedge resection. At first recurrence, segmental recurrence was observed in 18 patients (17.8%), while 28 patients (27.7%) were with sectional recurrence and 48 patients (47.5%) were with lobar recurrence. However, the cumulative recurrent sites of each patient showed extra recurrence in 53 patients (52.5%) at initial recurrence, 79 patients (78.2%) until the second recurrence, 89 patients (88.1%) until the third recurrence, 94 patients (93.0%) until the fourth, and 96 patients (95.0%) until the fifth recurrence. CONCLUSION: Some intrahepatic recurrence after wedge resection might have been avoided if anatomic resection had been performed instead. However, the number of contralateral or extrahepatic recurrences increased with the number of recurrences.

Distinct role of tumor-infiltrating lymphocytes between synchronous and metachronous colorectal cancer.

PURPOSE: Tumor-infiltrating lymphocytes (TILs) may influence the prognosis of colorectal liver metastasis (CRLM). We assessed the prognostic value of evaluating TILs in the primary and metastatic sites of synchronous CRLM as well as metachronous CRLM. METHODS: We examined 90 patients who underwent curative primary and liver metastasis resection for colorectal cancer. CD8+ TILs (cytotoxic T cells) or CD45RO+ TILs (memory T cells) in both primary and metastatic sites were simultaneously evaluated by immunohistochemistry. RESULTS: Fifty-one patients had synchronous CRLM, and 39 patients had metachronous CRLM. In synchronous cases, the overall survival (OS) was significantly worse in patients with low CD8+ or CD45RO+ TILs in a metastatic site than in those with high CD8+ or CD45RO+ TILs (P = 0.017 and P = 0.005, respectively). Multivariate analysis showed that age ≥ 65 years (P = 0.043), maximum tumor size ≥ 30 mm (P = 0.003), primary N2-3 (P = 0.019), and low CD8+ TILs in metastatic site (P = 0.046) were independent poor prognostic factors. In contrast, in metachronous cases, OS was significantly worse in patients with low CD45RO+ TILs in a primary site than in those with high CD45RO+ TILs (P = 0.021). CD45RO+ TILs in a primary site (P = 0.044) were determined to be independent prognostic factor on multivariate analysis. CONCLUSIONS: The immune microenvironment between synchronous and metachronous CRLM might be different, and these differences may affect its prognosis.

Pre- and postoperative C-reactive protein as a risk factor of organ/space surgical site infection after hepatectomy.

BACKGROUND: Organ/space surgical site infection (SSI) is one of the most common complications of liver resection, with significant impact on morbidity and mortality, so patients at high risk should be identified early. This study aimed to determine whether pre- and postoperative C-reactive protein (CRP) levels could predict organ/space SSIs. METHODS: The hospital records of consecutive patients who underwent hepatectomy without biliary reconstruction at our institutions between 2008 and 2015 were reviewed retrospectively. Preoperative, intraoperative, and postoperative variables were compared between patients with or without organ/space SSIs. Its risk factors were also determined. RESULTS: Among 443 identified patients, 55 cases (12.5%) developed organ/space SSIs; they more frequently experienced other complications and bile leakage (47.3% vs. 16.6%, p = 0.001; 40.0% vs. 8.5%, p < 0.001, respectively). Postoperative CRP elevation from postoperative day (POD) 3 to 5 was significantly more frequent in the SSI group (21.8% vs. 4.9%, p < 0.001). Multivariate analysis identified preoperative CRP ≥ 0.2 mg/dL (odds ratio (OR), 2.01, p = 0.044], preoperative cholangitis (OR, 15.7; p = 0.020), red cell concentrate (RCC) transfusion (OR, 2.61, p = 0.018), bile leakage (OR, 9.51; p < 0.001), and CRP level elevation from POD 3 to 5 (OR, 3.81, p = 0.008) as independent risk factors for organ/space SSIs. CONCLUSIONS: Preoperative CRP elevation and postoperative CRP trajectory are risk factors for organ/space SSIs after liver resection. A prolonged CRP level elevation at POD 5 indicates its occurrence. If there were no risk factors and no CRP elevation at POD 5, its presence could be excluded.

Clinical impact of sarcopenia in early-stage intrahepatic recurrent hepatocellular carcinoma: an association with impaired host immunity.

PURPOSE: This study investigated the role of sarcopenia in the long-term outcomes of patients with early-stage intrahepatic recurrent hepatocellular carcinoma (HCC). METHODS: The study included 136 patients with intrahepatic recurrent Barcelona Clinic Liver Cancer (BCLC) stage 0/A HCC following liver resection diagnosed between 2006 and 2020 and underwent surgery, radiofrequency ablation (RFA), or transcatheter arterial chemoembolization (TACE). Sarcopenia was defined based on the skeletal muscle index using computed tomography at the time of recurrence, and its association with long-term outcomes was evaluated. Tumor-infiltrating lymphocytes (CD4 + , CD8 + , and CD45RO + T cells) were assayed using immunohistochemistry on specimens obtained from repeat hepatectomies, and their association with sarcopenia was evaluated. RESULTS: The overall survival (OS) and recurrence-free survival (RFS) rates after initial recurrence of patients with sarcopenia were significantly lower than those without sarcopenia (p < 0.001 and p < 0.001, respectively). Multivariate analysis identified sarcopenia as an independent prognostic factor for RFS (p < 0.001). In patients without sarcopenia, surgery resulted in better RFS than RFA or TACE. Contrastingly, in patients with sarcopenia, the RFS was extremely poor regardless of the treatment type: surgery, RFA, or TACE (median RFS, 11.7, 12.7, and 10.1 months). Significantly low levels of tumor-infiltrating CD4 + , CD8 + , and CD45RO + lymphocytes were observed in patients with sarcopenia (p = 0.001, p = 0.001, and p = 0.001, respectively). CONCLUSIONS: This study suggests that patients with sarcopenia have poor RFS regardless of the treatment type for early-stage intrahepatic recurrent HCC. Impaired host immunity might be one of the underlying mechanisms.

Impact of laparoscopic liver resection on liver regeneration.

BACKGROUND: Liver regeneration after liver resection plays an important role in preventing posthepatectomy liver failure. In this study, we aimed to evaluate and compare the impact of laparoscopic liver resection (LLR) and open liver resection (OLR) on liver regeneration. METHODS: Patients who underwent curative anatomical liver resection for hepatocellular carcinoma, cholangiocellular carcinoma, and colorectal liver metastases at our institution between January 2010 and December 2018 were included in this study. The patients were divided into the OLR and LLR groups. Preoperative liver volume (PLV), future remnant liver volume, resected liver volume (RLV), liver volume at 1 month after the surgery, and liver volume at 6 months after the surgery were calculated. The liver regeneration rate was defined as the increase in the rate of RLV, and the liver recovery rate was defined as the rate of return to the PLV. RESULTS: The study included 72 patients. Among them, 43 were included in the OLR group and 29 were included in the LLR group. No differences were observed in the baseline characteristics and surgical procedures between the two groups. Moreover, no significant difference was observed in the liver regeneration rate at 1 month after the surgery (OLR vs. LLR: 68.9% vs. 69.0%, p = 0.875) and at 6 months after the surgery (91.8% vs. 93.2%, p = 0.995). Furthermore, the liver recovery rates were not significantly different between the two groups at 1 month after the surgery (90.3% vs. 90.6%, p = 0.893) and at 6 months after the surgery (96.9% vs. 98.8%, p = 0.986). CONCLUSION: Liver regeneration after liver resection is not affected by the type of surgical procedure and both laparoscopic and open procedures yield similar regeneration and recovery rates.

Clinically Relevant Late-Onset Biliary Complications After Pancreatoduodenectomy.

BACKGROUND: Late-onset biliary complications (LBC) after pancreatoduodenectomy (PD) can be serious. This study aimed to clarify the frequency and risk factors of severe LBC after PD. METHODS: We defined LBC as biliary complications occurring 3 months after PD and severe LBC as cases that required intensive care. A total of 318 patients who underwent PD between 2010 and 2018 with at least 1 year of postoperative follow-up were evaluated. RESULTS: Hospitalization for severe LBC was required in 59 patients (19%), of whom 20 had liver abscesses (6.3%); 18, acute cholangitis (5.7%); 12, biliary stones (3.8%); and 21, biliary strictures (6.6%). Interventional radiological or endoscopic treatment was required in 32 patients (10%), of whom 9 had a benign primary disease with biliary stones and/or strictures. Thirteen of the remaining 23 patients with a malignant primary disease had liver abscesses and cholangitis. Significant independent risk factors for severe LBC in patients with malignant primary disease were recurrence around the hepaticojejunostomy (odds ratio 6.5, P = 0.013) and chemotherapy (odds ratio 13.5, P < 0.001). CONCLUSIONS: Severe LBC after PD may occur regardless of whether the primary disease is benign or malignant. The course of severe LBC differs according to the primary disease, and therefore, appropriate follow-up and optimal treatment should be recommended according to the condition of the patient and the disease state.

Advantages of skin closure with subcuticular suture for liver resection on postoperative and cosmetic outcomes: a propensity matched analysis.

PURPOSE: The effects of subcuticular sutures on postoperative and cosmetic outcomes in patients who underwent liver resection have not been well studied. Here, we investigated the advantages of subcuticular suture compared to skin stapler regarding open liver resection. METHODS: We assessed 342 patients who underwent liver resection at Nara Medical University between 2008 and 2015. They were divided into two groups: subcuticular suture and staple groups. Baseline characteristics and perioperative outcomes were retrospectively compared using one-to-one propensity score matching analysis. RESULTS: In this period, 179 patients underwent skin closure with subcuticular sutures and 163 patients underwent skin closure with staples. After propensity matching, 85 pairs of cases were matched. The incidence of wound infection was similar in the two groups (3.5% in the subcuticular suture group and 9.4% in the staple group; p = 0.119). The length of hospital stay was significantly shorter in the subcuticular suture group than in the staple group (10 days vs 15 days; p < 0.001). In addition, the rate of patients who were discharged within 7 days after surgery was statistically higher in the subcuticular group (21.1% vs 3.5%, p = 0.001). Hypertrophic scar 6 months after surgery was significantly less frequent in the subcuticular group (9.4% vs 25.9%, p = 0.010). CONCLUSION: Subcuticular sutures might be advantageous for liver surgery reducing length of hospital stay and proportion of hypertrophic scar.

Integrative analysis identifies activated anti-tumor immune microenvironment in lung metastasis of pancreatic cancer.

BACKGROUND: Although the prognosis of patients experiencing recurrences after surgery for pancreatic cancer is extremely poor, patients who develop recurrence in the lung have a better prognosis compared to other types of recurrence. We performed a histo-immunological analysis of the metastatic specimens to identify specific features of this patient subgroup. METHODS: We performed immunohistochemistry for CD4+, CD8+, CD45RO+, Foxp3, and PD-L1 in the lung (n = 22), peritoneal (n = 18), and liver (n = 6) metastases of pancreatic cancer. As microenvironmental and immunonutritional investigations, the tumor-stroma ratio and prognostic nutritional index (PNI) were utilized in the integrative analysis of immunological features. RESULTS: We identified significantly increased tumor-infiltrating CD4+, CD8+, and CD45RO+ cells in lung metastasis, compared with peritoneal and liver metastases (lung vs. peritoneum/liver, CD4: P < 0.001/P = 0.015, CD8: P < 0.001/P = 0.038, CD45RO: P = 0.022/P = 0.012). The CD8/Foxp3 ratio was higher in the lung than in the liver (P = 0.024). PD-L1 expression was significantly higher in lung metastasis than in peritoneal metastasis (P = 0.010). Furthermore, we found that lung metastasis had fewer cancer stroma than peritoneal metastasis (P < 0.001). A higher PNI was observed in patients with lung metastasis, and PNI was positively correlated with tumor-infiltrating lymphocytes in metastatic sites. CONCLUSION: We identified that lung metastasis revealed an immunologically "hot" tumor with increased TILs and PD-L1 expression. This specific feature suggests that patients with lung metastasis can be candidates for immunotherapy, such as immune checkpoint inhibitors; therefore, our study provides a framework for developing individualized treatment strategies for this patient subgroup.

Clamp-Crush Technique for Laparoscopic Liver Resection.

Liver parenchymal transection is the most important process in laparoscopic liver resection (LLR). Various surgical methods and devices for LLR have been applied including the cavitron ultrasonic surgical aspirator, ultrasonic scalpel, and staplers. Very few reports have investigated the clamp--crush technique for LLR.1,2 Current study shows a clamp-crush technique for LLR and evaluates its perioperative outcomes. The clamp-crush technique was performed using simple forceps and the Pringle maneuver under a low central venous pressure. The vessels that remained after crushing were clipped if they were thick; or removed with an ultrasonic cutting-coagulation system if they were thin. Sixty-one LLRs were performed using the clamp-crush technique. Pathological cirrhosis was observed in 22 patients (36.0%). The types of resection were as follows: 31 wedge resections (50.8%), 11 segmentectomies (19.0%), 9 sectionectomies (14.8%), and 10 hemihepatectomies (16.4%). The intraoperative blood loss was 62 ml; the surgical duration was 272 min. The postoperative major complication (Clavien-Dindo ≥ IIIa) rate was 4.9%. The median hospital stay was 8 days (range = 4-53 days). A 76-year-old female underwent right LLR for a 9-cm HCC. The right hepatic artery and portal vein were dissected separately. After mobilizing the liver, parenchymal transection was performed using the clamp-crush technique. The middle hepatic vein was totally exposed. Intraoperative blood loss was 32 ml and the surgical duration was 5 h 32 min with no postoperative complications. The clamp-crush technique is safe and feasible for LLR and could contribute to quick parenchymal transection and flattening of the transection plane.

Clinical Importance of CD200 Expression in Colorectal Liver Metastasis.

BACKGROUND: Approximately 30% of patients diagnosed with colorectal cancer (CRC) develop liver metastases. We evaluated the role of CD200, a potent immunosuppressive molecule, in colorectal liver metastases (CRLM). METHODS: We examined 110 patients who underwent curative liver resection for CRLM at our institution between 2000 and 2016. Based on the results of immunohistochemical analysis, the patients were divided into high-CD200 (n = 47) and low-CD200 (n = 63) expression groups. The relationships between CD200 expression and various clinicopathological outcomes were investigated. RESULTS: The overall survival (OS) of patients in the high-CD200 group was significantly worse than that in the low-CD200 group (p = 0.009). Multivariate analysis showed that the independent prognostic factors in CRLM were maximum tumor size > 30 mm (p = 0.002), preoperative carcinoembryonic antigen level > 20 ng/mL (p < 0.001), primary CRC N2-3 (p = 0.049), and high-CD200 expression (p = 0.004). Furthermore, CD4+, CD8+, and CD45RO+ tumor-infiltrating lymphocytes in CRLM were significantly higher in the low-CD200 group than in the high-CD200 group (p = 0.005, p = 0.001, and p < 0.001, respectively). In addition, patients who had received preoperative chemotherapy had higher CD200 expression than those who had not received preoperative chemotherapy, and OS was significantly worse in patients in the high-CD200 group who had received preoperative chemotherapy. CONCLUSIONS: CD200 expression was an independent prognostic factor in CRLM. CD200 may play a critical role in tumor immunity in CRLM, and can therefore be used as a potential therapeutic target in CRLM.

Pulmonary complications after laparoscopic liver resection.

BACKGROUND: Although postoperative pulmonary complications (PPCs) are one of the common complications after liver surgery and might be avoided with the use of a laparoscopic approach, few reports have focused on the comparison of PPCs between laparoscopic liver resection (LLR) and open liver resection (OLR). The aim of this study was to clarify the effect of LLR on PPCs. METHODS: The study included 307 patients who underwent liver resection, excluding biliary reconstruction, at our institution between 2014 and 2018. Patients were divided into the OLR and LLR groups. The perioperative outcomes and PPCs were compared between the two groups using propensity score matching. On day 3 after liver surgery, all patients had chest radiography to confirm the presence of pleural effusion, including cases that required thoracentesis, and pneumonia. RESULTS: Of the 307 patients, 172 and 135 patients were included in OLR and LLR groups, respectively. After propensity score matching, 65 patients were included in each group. Compared with the matched OLR group, the matched LLR group had significantly lower intraoperative blood loss (P < 0.001); rate of intraoperative blood transfusion (P = 0.011); overall PPCs (P = 0.032); and number of cases with chest radiography-confirmed pleural effusion (P = 0.048), pleural effusion requiring thoracentesis (P = 0.029), and pneumonia (P = 0.012). Moreover, postoperative hospital stay was significantly shorter in the matched LLR group than in the matched OLR group. CONCLUSIONS: Compared with OLR, LLR might be a better surgical approach to avoid PPCs.

Outcomes in Patients with Chronic Kidney Disease After Liver Resection for Hepatocellular Carcinoma.

BACKGROUND: The aim of this study was to clarify the feasibility of liver resection in hepatocellular carcinoma (HCC) patients with chronic kidney disease (CKD). METHODS: In all, 204 patients who underwent primary liver resection for HCC between 2011 and 2019 were analyzed. Short-term and long-term outcomes were compared between the CKD and control groups. The CKD group was defined by a preoperative estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2 and chronic kidney disease Stage 3B or higher. RESULTS: Twenty-eight patients (13.7%) had CKD. No significant differences were observed in the overall complication rates between the groups (46.4% vs. 34.7% p = 0.229). The incidence of bile leakage was significantly higher in the CKD group than in the control group (14.3% vs. 4.0% p = 0.048), and the median postoperative hospital stay was significantly longer in the CKD group (11 vs. 9 days p = 0.031). No significant differences were found in the disease-free survival between the two groups (p = 0.763), but overall survival (OS) was significantly worse in the CKD group than in the control group (p = 0.022). In the multivariable analysis, a CKD diagnosis (hazard ratio, 2.261; 95% confidence interval (CI), 1.139-4.486 p = 0.020) was identified as an independent poor prognostic factor for OS. The percentage of patients who died from cardiovascular disease was significantly higher in the CKD group (27.3% vs. 2.3% p = 0.023). CONCLUSIONS: Liver resection for HCC in CKD patients is associated with acceptable perioperative outcomes. However, cardiovascular disease may negatively affect the OS of CKD patients after liver resection.

Influence of the Glissonean Pedicle Transection Approach in Spiegel Lobe-Preserving Left Hepatectomy on Spiegel Lobe Volume and Remnant Liver Functions.

BACKGROUND: The extrahepatic surgical technique in liver resection can be divided into glissonean pedicle transection and glissonean separated transection approaches. In this study, we compared remnant liver function and liver regeneration involving the Spiegel lobe between these two approaches regarding Spiegel lobe-preserving left hepatectomy. METHODS: We enrolled 31 patients who underwent Spiegel lobe-preserving left hepatectomy for malignant hepatobiliary diseases between April 2008 and January 2020. The postoperative Spiegel lobe volume was measured using a volume analyzer at 3 and 6 months postoperatively. RESULTS: Of the 31 patients, 22 and 9 were included in the glissonean separated transection and glissonean pedicle transection groups, respectively. There was no significant between-group difference in the preoperative Spiegel lobe volume. However, the volumes at 3 and 6 months postoperatively were significantly larger in the glissonean pedicle transection group than in the glissonean transection group (29.92 mL vs. 13.00 mL; P < 0.001 and 28.43 mL vs. 15.01 mL; P < 0.001, respectively). There was no significant between-group difference in postoperative remnant liver function. CONCLUSIONS: The postoperative Spiegel lobe volume was larger, and liver regeneration was better with the glissonean pedicle transection approach because of transection for Spiegel branch of the portal vein. It is desirable to preserve Spiegel branch in possible cases when surgeons select the glissonean separated transection approach based on the location and size of the tumors.

Significance of Herpesvirus Entry Mediator Expression in Human Colorectal Liver Metastasis.

BACKGROUND: Herpesvirus entry mediator (HVEM) has been suggested to play various roles in cancer biology. The authors report that HVEM expression in tumor cells is associated with a reduction in the number of tumor-infiltrating lymphocytes and a poor prognosis after surgical resection in various human gastrointestinal cancers. This study aimed to clarify the clinical significance of HVEM expression in human colorectal liver metastasis (CRLM). METHODS: This study examined the cases of 104 patients with CRLM who underwent curative liver resection at Nara Medical University between 2000 and 2014. The median follow-up period was 50.2 months. Immunohistochemical staining was performed using antibodies against HVEM, CD4, CD8, and CD45RO. RESULTS: High HVEM expression was observed in 49 patients (47.1%) with CRLM. Expression of HVEM was not associated with age, gender, administration of preoperative chemotherapy, tumor size, number of tumors, or histologic differentiation. The high-HVEM group exhibited significantly worse overall survival (OS) than the low-HVEM group (P = 0.002). Multivariate analysis showed that high HVEM expression in CRLM, age of 70 years or older, and having five or more tumors are independent poor prognostic factors for OS (hazard ratio [HR], 3.35; 95% confidence interval [CI], 1.41-7.93; P = 0.006). The number of tumor-infiltrating CD8+ and CD45RO+ T cells was significantly lower in the high-HVEM group than in the low-HVEM group. High HVEM expression in primary colorectal cancer was significantly associated with synchronous CRLM, but not with metachronous CRLM. CONCLUSIONS: Tumor HVEM expression might play a critical role in CRLM.