Prognostic value of preoperative geriatric nutritional risk index in intrahepatic cholangiocarcinoma after hepatectomy: a single­center retrospective cohort study.

AIM: Patients with malignant tumors are prone to develop nutritional disorders. The Geriatric Nutritional Risk Index (GNRI) is a new prognostic indicator for assessing the nutritional status. This study was performed to evaluate whether the preoperative GNRI can serve as a prognostic factor in patients with intrahepatic cholangiocarcinoma (ICC) undergoing curative surgery. METHODS: This study included 123 consecutive patients with ICC who were treated with curative surgery. Kaplan-Meier analysis was performed to calculate the recurrence-free survival (RFS) and overall survival (OS), and Cox regression analysis was used to evaluate prognostic factors. RESULTS: Of the 123 patients, 82 were male and 41 were female. The median age of the patients was 70 years, and the median follow-up period was 37.0 months (interquartile range, 16.2-71.7 months). The patients were classified by the median GNRI into a low GNRI group (GNRI < 105) and high GNRI group (GNRI ≥ 105). The patients in the low GNRI group had a significantly poorer prognosis in terms of RFS and OS than the patients in the high GNRI group (RFS, p = 0.0201; OS, p < 0.0001). Lymph node metastasis [hazard ratio (HR), 4.66; 95% confidence interval (CI), 2.46-8.85], postoperative complications (HR, 2.38; 95% CI, 1.32-4.31), and a low GNRI (HR, 2.53; 95% CI, 1.42-4.50) were independent poor prognostic factors for OS. CONCLUSION: The GNRI may be a useful prognostic indicator in patients with ICC undergoing curative hepatectomy.

Perioperative disabilities in activities of daily living are associated with worse prognosis after hepatectomy for colorectal liver metastasis.

BACKGROUND: The number of vulnerable patients with colorectal liver metastasis (CRLM) has increased. This study aimed to clarify the relationship between perioperative activities of daily living (ADL) and clinical outcomes after hepatectomy for CRLM. METHODS: Consecutive patients undergoing resection of CRLM from 2004 to 2020 were included. Pre- or postoperative ADL was evaluated according to Barthel index (BI) scores, which range from 0 to 100. Higher scores represent greater level of independence in ADL. Pre- or postoperative BI scores of ≤85 were defined as perioperative disabilities in ADL. Multivariable Cox proportional hazard regression models were utilised to estimate adjusted hazard ratios (HRs) and confidence interval (CI). RESULTS: A total of 218 patients were included, 16 (7.3%) revealed preoperative BI scores of ≤85, and 32 (15%) revealed postoperative BI scores of ≤85. In multivariate analyses, the perioperative disabilities in ADL were independently associated with shorter overall survival (HR, 1.96; 95% CI, 1.10-3.31; P = 0.023) and cancer-specific survival (HR, 2.31; 95% CI, 1.29-3.92; P = 0.006). CONCLUSION: Perioperative disabilities in ADL were associated with poor prognosis following hepatectomy for CRLM. Improving preoperative vulnerability and preventing functional decline after surgery may provide a favourable prognosis for patients with CRLM.

The Prognostic Role of Serine Racemase in Patients With Pancreatic Cancer: A New Marker in Cancer Metabolism.

OBJECTIVES: Serine racemase (SRR) participates in serine metabolism in central nervous systems. Serine racemase is only studied in colorectal cancer, and its role in pancreatic cancer (PC) is unknown. This study aims to investigate the role of SRR in PC. METHODS: Totally 182 patients with PC were enrolled in this study. Slices from patients were stained for SRR and CD8+ T cells. Kaplan-Meier methods were used to do survival analysis according to SRR expression from immunohistochemical staining. Univariate and multivariate Cox regression analysis was performed to clarify the independent prognostic value of SRR. Bioinformatic tools were used to explore and validate the expression, prognostic value, possible mechanism, and immune interaction of SRR in PC. RESULTS: The expression of SRR was lower in tumor tissue than normal tissue, also potentially decreased with the increasing tumor grade. Low SRR expression was an independent risk factor for overall survival (hazards ratio, 1.875; 95% confidence interval, 1.175-2.990; P = 0.008) in patients with PC. Serine racemase was positively correlated with CD8+ T cells infiltration and possibly associated with CCL14 and CXCL12 expression. CONCLUSIONS: Serine racemase plays a prognostic role in PC and may be a potentially therapeutic target.

Distinct approaches (antecolic and retrocolic) according to tumor location in laparoscopic and endoscopic cooperative surgery for non-ampullary duodenum tumors.

AIM: Laparoscopic and endoscopic cooperative surgery for early non-ampullary duodenum tumors (D-LECS) is now noted because of its safety and lower invasiveness. Here, we introduce two distinct approaches (antecolic and retrocolic) according to the tumor location during D-LECS. METHODS: From October 2018 to March 2022, 24 patients (25 lesions) underwent D-LECS. Two (8%), two (8%), 16 (64%), and five (20%) lesions were located in the first portion, in the second portion to Vater's papilla, around the inferior duodenum flexure, and in the third portion of the duodenum, respectively. The median preoperative tumor diameter was 22.5 mm. RESULTS: Antecolic and retrocolic approaches were employed in 16 (67%) and 8 (33%) cases, respectively. LECS procedures, such as two-layer suturing after full-thickness dissection and laparoscopic reinforcement by seromuscular suturing after endoscopic submucosal dissection (ESD), were performed in five and 19 cases, respectively. Median operative time and blood loss were 303 min and 5 g, respectively. Intraoperative duodenal perforations occurred in three of 19 cases during ESD; however, they were successfully laparoscopically repaired. Median times until start diet and postoperative hospital stay were 4.5 and 8 days, respectively. Histological examination of the tumors revealed nine adenomas, 12 adenocarcinomas, and four GISTs. Curative resection (R0) was achieved in 21 cases (87.5%). In a comparison of the surgical short outcomes between antecolic and retrocolic approaches, there was no significant difference. CONCLUSION: D-LECS can be a safe and minimally invasive treatment option for non-ampullary early duodenal tumors, and two distinct approaches according to the tumor location are feasible.

Disability in perioperative activities of daily living is associated with worse survival outcomes following hepatic resection in patients with intrahepatic cholangiocarcinoma.

AIM: Intrahepatic cholangiocarcinoma (ICC) is a rare disease; however, its incidence and mortality are increasing worldwide. The rapid aging of populations around the world is leading to an increased number of patients with cancer who develop disability in activities of daily living (ADL). This study was conducted to investigate the associations of perioperative ADL with patient survival after hepatic resection for ICC. METHODS: We included 70 consecutive patients who underwent hepatectomy for ICC from 2010 to 2021 in the current study. Preoperative and postoperative ADL were evaluated based on the Barthel index, which yields a score of 0-100 points, with higher scores indicating greater independence. A preoperative or postoperative Barthel index score of <100 was defined as disability in perioperative ADL. Cox proportional hazards regression was used to calculate hazard ratios after adjusting for potential confounders. RESULTS: Among the 70 patients, seven (10%) had a preoperative Barthel index score of <100, and 23 (33%) showed a postoperative Barthel index score of <100. Multivariate analyses revealed that disability in perioperative ADL was associated with shorter recurrence-free survival (multivariable hazard ratios 2.38, 95% confidence interval 1.22-4.57; p = 0.011) and overall survival (multivariable hazard ratio 2.49, 95% confidence interval 1.09-5.70; p = 0.031). CONCLUSIONS: Disability in perioperative ADL is associated with shorter recurrence-free and overall survival after hepatic resection for ICC. Upon validation, perioperative measurement of ADL may improve risk assessment, and improvement of perioperative ADL may lead to favorable clinical outcomes in patients with ICC.

[The Usefulness of RFA as a Conversion Therapy after Molecular Targeted Therapy for Advanced Hepatocellular Carcinoma-A Case of Long-Term Survival with Multidisciplinary Treatment].

In this study, we report a case in which molecular-targeted agents have been shown to be effective in the treatment of unresectable hepatocellular carcinoma(HCC), which has enabled a radical treatment, conversion therapy, and long-term survival with multimodality treatment including RFA. Case: A 61-year-old male, abdominal ultrasonography revealed a large liver tumor and multiple lesions mainly in the right lobe of the liver. He was diagnosed as having unresectable HCC, and treatment with sorafenib was initiated. After treatment, the tumor was clearly reduced in size and the lung metastases disappeared. Five years later, recurrence was observed at the treated site of S7/8, and RFA was performed again after TACE. The patient has survived for 8 years without recurrence.

Effect of the Gant-Miwa-Thiersch Procedure for Rectal Prolapse on the Mesorectum.

Rectal prolapse (RP) most commonly occurs among elderly women and is caused by vulnerable suspensory tissue in the pelvis. In Japan, the Gant-Miwa-Thiersch procedure (GMT) is recommended for elderly people with poor general health. We retrospectively analyzed clinical data from 12 patients who underwent GMT at our hospital from September 2005 to July 2021 and investigated the effect of GMT on the mesorectum using abdominal-pelvic computed tomography (CT) performed for other diseases. The median age of the cohort was 82 years, and 92% of the subjects were women. The median RP length was 5 cm, and the median follow-up period was 60 months. Recurrence was observed in 1 of 12 patients (8.0%). CT conducted before and more than 6 months after GMT revealed no abnormal findings in the mesorectum, whereas CT within 5 months after GMT revealed hyperdense fat in the mesorectum in all three patients (100%; P < 0.05). The RP recurrence rate after the GMT was low. The mechanism of the effect of GMT may involve not only a direct mucosal plicating effect but also adhesional rectosacral fixation due to the presence of inflammation extending to the mesorectum.

Prognostic Value of the Preoperative Tumor Marker Index in Resected Pancreatic Ductal Adenocarcinoma: A Retrospective Single-Institution Study.

BACKGROUND: The prediction of prognostic outcomes can provide the most suitable strategy for patients with pancreatic ductal adenocarcinoma (PDAC). This study aimed to evaluate the clinical value of the preoperative tumor marker index (pre-TI) in predicting prognostic outcomes after resection for PDAC. METHODS: For 183 patients who underwent pancreatic resection of PDAC, adjusted carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), pancreatic cancer-associated antigen-2 (DUpan-2), and s-pancreas-1 antigen (SPan-1) were retrospectively evaluated, and the positive number of these markers was scored as the pre-TI. RESULTS: A high pre-TI (≥ 2) was significantly associated with a larger tumor and lymph node metastases, and the patients with a high pre-TI had worse prognostic outcomes in terms of both relapse-free survival (RFS) (P < 0.0001, log-rank) and overall survival (OS) (P < 0.0001, Λlog-rank) than the patients with a low pre-TI. The pre-TI was one of the independent factors of a poor prognosis for RFS (hazard ratio [HR], 2.36; P < 0.0001) and OS (HR, 2.27; P < 0.0001). In addition, even for the patients with normal adjusted CA19-9 values (n = 74, 40.4%), those with the high pre-TI had a significantly poorer prognosis than those with a low pre-TI (RFS: P = 0.002, log-rank; OS: P = 0.031, log-rank). CONCLUSIONS: The pre-TI could be a potent predictive marker of prognostic outcomes for patients with resections for PDAC. Patients with a high pre-TI may need additional strategies to improve their prognosis.

Thoracoscopic surgery for hepatocellular carcinoma located in the hepatic dome: Technical aspect and oncological results.

INTRODUCTION: The objective of this study was to describe the surgical techniques for a thoracoscopic approach to treat hepatocellular carcinoma in the hepatic dome. Also, safety, feasibility, and long-term outcomes were evaluated. METHODS: Surgical procedures were selected based on liver function, the extent and location of the tumor, and each patient's general condition. Thoracoscopic hepatic resection was performed under direct vision through a diaphragmatic incision. Thoracoscopic radiofrequency ablation (TRFA) was performed either with a transdiaphragmatic puncture for deeply located tumors or under direct vision through a diaphragmatic incision for subcapsular tumors. RESULTS: Thoracoscopic surgery was indicated for 107 patients with hepatocellular carcinoma in the hepatic dome. Among these patients, 5 underwent hepatectomy and 102 underwent radiofrequency ablation, which was more frequently employed in patients with impaired liver function. Of the patients who underwent radiofrequency ablation, 43 (42.2%) required a diaphragmatic incision. In the thoracoscopic hepatic resection group and TRFA group, the median operating time was 350 and 197 minutes, the median blood loss was 200 and 5 mL, and the complication rate was 12.7% and 20.0%, respectively. The 5-year overall and disease-free survival rates were 100% and 50.0% in the thoracoscopic hepatic resection group, respectively, and 60.7% and 18.1% in the TRFA group, respectively. Local recurrence after TRFA was observed in 10 patients (9.8%). CONCLUSION: The thoracoscopic approach is safe and feasible, with promising short- and long-term outcomes. It could serve as a treatment option for hepatocellular carcinoma in the hepatic dome.

Postoperative nonalcoholic fatty liver disease is correlated with malnutrition leading to an unpreferable clinical course for pancreatic cancer patients undergoing pancreaticoduodenectomy.

PURPOSES: This study aimed to clarify the impact of postoperative nonalcoholic fatty liver disease (NAFLD) on the clinical course of patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: One hundred and eight patients with pancreatic cancer undergoing pancreaticoduodenectomy (PD) with curative intent in between 2005 and 2016 were enrolled in this study. Post-PD NAFLD was assessed by computed tomography (CT), which was routinely performed at 3 months, 6 months, and 1 year after surgery. The clinical impact of post-PD NAFLD was examined from an oncological perspective. RESULTS: There were 50 (46.2%) post-PD NAFLD patients. The NAFLD group showed significantly lower CT values at 3 months, 6 months, and 1 year after surgery than those without NAFLD. Patients with NAFLD showed significant body weight loss and a decrease in serum albumin level after surgery compared with those without NAFLD. Consequently, the 70% completion rate of adjuvant chemotherapy with gemcitabine, but not S1, was significantly lower in the NAFLD group than in the non-NAFLD group. The 5-year overall survival and disease-free survival rates were comparable between the two groups. CONCLUSION: Post-PD NAFLD was associated with malnutrition in patients with PDAC, reducing their tolerance to gemcitabine-based adjuvant chemotherapy. Post-PD NAFLD needs to be emphasized and requires special nutritional intervention in patients with PDAC.

Clinical Significance of PD-L1 Expression in Both Cancer and Stroma Cells of Cholangiocarcinoma Patients.

BACKGROUND: The clinical significance of programmed death 1 and its ligand (PD-L1) as therapeutic targets has been reported previously. This study aimed to investigate the clinical impact of PD-L1 expression in cancer and stroma cells in cholangiocarcinoma (CCA). METHODS: The study enrolled 177 consecutive CCA patients who underwent curative resection between 2005 and 2014. Expression of PD-L1 in CCA and stroma cells was assayed by immunohistochemistry, and their relationships with patient clinicopathologic characteristics and prognoses were evaluated. Tumor-infiltrating immune cells (CD66b+ neutrophils [TANs] and CD163+ M2 macrophages [TAMs]) also were assayed by immunohistochemistry, and their relationship with PD-L1 expression in cancer and stroma cells was evaluated. RESULTS: Among the 177 analyzed CCA cases, PD-L1 expression was identified in cancer cells in 54 cases (30.5%) and in stroma cells in 77 cases (43.5%). The patients with positive PD-L1 expression in cancer and stroma cells had worse overall survival rates than those negative for PD-L1 (cancer cells: hazard ratio [HR] 2.08; P = 0.0004; stroma cells: HR 1.84; P = 0.003). Moreover, the patients with PD-L1-positive cancer cells had higher rates of PD-L1 expression in stroma cells (P < 0.0001) and higher numbers of TANs (P = 0.0003) and TAMs (P = 0.004) than those with low PD-L1 expression. In the multivariate analysis, PD-L1 expression in both cancer and stroma cells (HR 2.20; P = 0.002) was an independent predictor of poor overall survival. CONCLUSIONS: The study showed PD-L1 expressed in both CCA and stromal cells and demonstrated that its expression may affect numbers of TANs and TAMs and play a pivotal role in CCA outcomes.

Clinical role of serum programmed death ligand 1 in patients with hepatocellular carcinoma: Where does it come from?

PURPOSES: Programmed death ligand 1 (PD-L1) is a key target for the treatment of several malignancies. The present study was conducted to clarify the role of serum PD-L1 in hepatocellular carcinoma (HCC). METHODS: Serum PD-L1 (sPD-L1) was examined by an enzyme-linked immunosorbent assay in 153 patients with HCC who underwent curative hepatectomy at Kumamoto University in 2011-2016. The expression of PD-L1 in tissue (tPD-L1) was investigated by immunohistochemistry. The clinical roles of the PD-L1 expression in both serum and tissue were examined. RESULTS: The sPD-L1 was significantly elevated in HCC patients compared to patients without any malignant or inflammatory disease (234 vs. 93 pg/mL, p < 0.0001). The percentage of the tPD-L1-positive area (%tPD-L1) in the background liver was significantly higher than in the tumor (1.52% vs. 0.48%, p < 0.0001). The %tPD-L1 in the background liver but not in the tumor was significantly correlated with the sPD-L1 level (p = 0.0079). The sPD-L1, %tPD-L1 in the tumor, and %tPD-L1 in the background liver were not correlated with the overall survival after surgery. CONCLUSION: PD-L1-expressing cells in the background liver, but not in the tumor tissue, appeared to contribute to the sPD-L1 level. The sPD-L1 level may thus not indicate the tumor burden in patients with HCC.

Endoscopic hepatic resection and endoscopic radiofrequency ablation as initial treatments for hepatocellular carcinoma within the Milan criteria.

PURPOSES: The indication of endoscopic (laparoscopic and thoracoscopic) hepatic resection (HR) has been expanded in the past decade because of its low invasiveness. However, the indications of endoscopic HR and radiofrequency ablation (RFA) have not yet been determined. METHODS: Among the 906 patients hospitalized for the initial treatment of hepatocellular carcinoma (HCC) between 2000 and 2017, 77 underwent endoscopic partial HR (E-pHR), and 94 underwent endoscopic RFA (E-RFA). We compared the short- and long-term outcomes between the E-pHR and E-RFA groups. RESULTS: The patients in the E-RFA group were characterized primarily by an impaired liver function. Among the patients with liver damage B or C, the overall survival (OS) in the E-pHR group was significantly worse than in the E-RFA group (3-year OS: 36% vs. 82%, p = 0.003). CONCLUSION: E-RFA may be recommended for the initial treatment of HCC in patients with a severely impaired liver function. However, E-pHR should be avoided as the initial treatment of HCC in such patients.

Clinical Significance of Preoperative Hepatocellular Carcinoma With High Lens culinaris Agglutinin-reactive Fraction of Alpha-Fetoprotein, But Low Alpha-Fetoprotein.

BACKGROUND: The aim of this study was to verify the significance of high Lens culinaris agglutinin-reactive fraction of α-fetoprotein (AFP-L3) in patients with hepatocellular carcinoma (HCC) with low AFP. MATERIALS AND METHODS: There were 283 patients with low AFP who underwent initial hepatic resection with or without radiofrequency ablation for HCC. Patients were divided into two groups based on AFP-L3 values: >10%: high AFP-L3 (n=24); and ≤10%: low AFP-L3 (n=259). Overall survival (OS) and 2-year recurrence rates were compared, and independent prognostic factors were identified. RESULTS: The OS and 2-year recurrence rates of the high AFP-L3 group were significantly worse than those of the low AFP-L3 group. The independent prognostic factors for poor OS were des-gamma-carboxy prothrombin (DCP) of >40 mAU/ml, microvascular invasion, and invasive growth, and those for 2-year recurrence were 99mTc-galactosyl human serum albumin uptake ratio of <0.90, DCP of >40 mAU/ml, multiple tumors, microvascular invasion, and poor differentiation. DCP levels increased with AFP-L3, and cases with high DCP and AFP-L3 had worse prognoses and higher 2-year recurrence rates compared to those with elevation of only one of these. CONCLUSION: Patients with high AFP-L3 but low AFP have poor prognosis and high 2-year recurrence rates. DCP strongly reflects HCC malignancy in patients with low AFP.

Cellular Senescence, Represented by Expression of Caveolin-1, in Cancer-Associated Fibroblasts Promotes Tumor Invasion in Pancreatic Cancer.

BACKGROUND: The role of senescence of cancer-associated fibroblasts (CAFs) in the development of cancer is controversial. In this study, we investigated whether cellular senescence of CAFs, represented by CAV1 expression, affects tumor progression in pancreatic cancers (PC). METHODS: Because CAV1 plays a major role in cellular senescence, we used CAV1 expression to monitor cellular senescence. A total of 157 consecutive patients with PC who underwent curative resection were enrolled in the study. Patients were divided into two groups according to CAV1 expression in CAFs by immunohistochemistry. We investigated the relationship between the CAV1 expression in CAFs and the patients' clinicopathological characteristics, including survival. We also established ten CAFs cell lines using PC clinical samples and chose one of them to knock down CAV1 expression. Finally, we cultured a PC cell line (MIAPaCa-2) in CAF-conditioned medium (CM). RESULTS: Regarding patients' clinicopathological characteristics, the serum levels of carbohydrate antigen 19-9 and the rate of advanced tumor stage (pT2, 3, and 4) were significantly higher in the high-CAV1 group. The high-CAV1 group had significantly worse outcomes in both overall and disease-free survival (p < 0.01). Additionally, in co-culture assays using CAFs-CM and MIAPaCa-2 cells, we found that knockdown of CAV1 in CAFs negatively affected the invasion of PC cells. CONCLUSIONS: In PC, CAV1 expression in CAFs is associated with patients' poor prognosis and the downregulation of CAV1 in CAFs reduces the invasiveness of PC cells. Therefore, CAV1 of CAFs might be a new target for the treatment of PC.

Clinical role of fludeoxyglucose (18F) positron emission tomography/computed tomography (18F-FDG PET/CT) in patients with pancreatic neuroendocrine tumors.

PURPOSES: Clinical predictive markers for the malignant potential of pancreatic neuroendocrine tumors (PNETs) are limited without histological investigation. We reported previously that a loss of the regular enhancement pattern in preoperative computed tomography (CT) was correlated with the malignant tumor phenotype. This study aimed to establish whether the metabolic aspect of the tumor evaluated by fludeoxyglucose (18F) positron emission tomography/computed tomography 18F-FDG PET/CT is associated with the tumor imaging characteristics and postoperative oncological outcome. METHODS: Among 77 patients who underwent surgery with curative intent for a PNET at our institution between 2001 and 2017, 24 who received 18F-FDG PET/CT before surgery were enrolled in this study. The clinical importance of the standardized uptake value (SUVmax) was investigated with regard to tumor progression and prognosis after curative surgery. RESULTS: There were four (16%) patients with insulinoma. The mean tumor size was 17 mm and when the median value of the SUVmax (= 2.0) was measured as the cut-off value, the SUVmax ≥ 2.0 group (n = 12) was associated with large tumor size (p = 0.021), high tumor grade (p = 0.015), and irregular pattern on CT (p = 0.0055). The SUVmax was not correlated with age, gender, whether the tumor was functioning or non-functioning, or lymph node metastasis. The SUVmax ≥ 2.0 group had significantly poorer disease-free survival (median, 3.5 vs 16.2 months; p = 0.023) and poorer overall survival (median, 8.8 vs 16.2 months; p = 0.042). CONCLUSION: An SUVmax ≥ 2.0 on 18F-FDG PET/CT might be associated with higher malignant potential of PNETs.

PD-L1 expression enhancement by infiltrating macrophage-derived tumor necrosis factor-α leads to poor pancreatic cancer prognosis.

Immunotherapy using anti-PD-1/PD-L1 antibodies for several types of cancer has received considerable attention in recent decades. However, the molecular mechanism underlying PD-L1 expression in pancreatic ductal adenocarcinoma (PDAC) cells has not been clearly elucidated. We investigated the clinical significance and regulatory mechanism of PD-L1 expression in PDAC cells. Among the various cytokines tested, tumor necrosis factor (TNF)-α upregulated PD-L1 expression in PDAC cells through NF-κB signaling. The induction of PD-L1 expression was also caused by co-culture with activated macrophages, and the upregulation was inhibited by neutralization with anti-TNF-α antibody after co-culture with activated macrophages. PD-L1 expression in PDAC cells was positively correlated with macrophage infiltration in tumor stroma of human PDAC tissues. In addition, survival analysis revealed that high PD-L1 expression was significantly associated with poor prognosis in 235 PDAC patients and especially in patients harboring high CD8-positive T-cell infiltration. These findings indicate that tumor-infiltrating macrophage-derived TNF-α could be a potential therapeutic target for PDAC.

Multimodal radiofrequency ablation versus laparoscopic hepatic resection for the treatment of primary hepatocellular carcinoma within Milan criteria in severely cirrhotic patients: long-term favorable outcomes over 10 years.

BACKGROUND: Less invasiveness is an important consideration for the treatment of hepatocellular carcinoma (HCC) especially in patients with severe cirrhosis. METHODS: Between April 2000 and September 2016, 100 patients with liver damage B underwent multimodal radiofrequency ablation (RFA; n = 62) or laparoscopic hepatic resection (Lap-HR; n = 38) for primary HCC as defined by the Milan criteria. We compared the operative outcomes and patients' survival between the two groups. RESULTS: The RFA group showed worse liver functions as indicated by indocyanine green retention rate (32.9 vs. 22.4%; p < 0.0001) and serum albumin value (3.3 vs. 3.6 g/dl; p = 0.0029). As expected, RFA was less invasive, as indicated by the differences in operation time (166 vs. 288 min.; p < 0.0001) and blood loss (8 vs. 377 g; p < 0.0001). There was no significant difference in the morbidity rate between the two groups; however, the duration of hospital stay of the RFA group was significantly shorter (7 vs. 11 days; p = 0.0002). There were no significant between-group differences regarding overall or disease-free survival. CONCLUSION: Multimodal RFA for HCC in patients with severe cirrhosis is associated with less invasiveness and shorter hospital stays, with no compromise in the patients' survival. In patients with severe cirrhosis, it may be time to consider changing the standard treatment for primary HCC within the Milan criteria to multimodal RFA.

Prognostic value of LINE-1 methylation level in 321 patients with primary liver cancer including hepatocellular carcinoma and intrahepatic cholangiocarcinoma.

BACKGROUND: The methylation level of long interspersed nucleotide element-1 (LINE-1) is a good surrogate marker of the global DNA methylation level. The relationship between LINE-1 methylation level and prognosis in primary liver cancer (PLC) patients remains unclear. RESULTS: LINE-1 methylation levels were significantly lower in HCC and cHCC-CC tissues, but not in ICC tissues, than those in noncancerous liver parenchyma (HCC: p < 0.0001; cHCC-CC: p < 0.001; and ICC: p = 0.053). HCC cases with hypomethylated LINE-1 had significantly shorter relapse-free survival (RFS) (log-rank, p = 0.008); however, this was not observed for the cHCC-CC or ICC cases. Multivariate Cox regression analysis revealed a significantly higher HCC recurrence rate in the group with hypomethylated LINE-1 (hazard ratio, 1.62; 95% confidence interval, 1.06-2.58; p = 0.025). CONCLUSIONS: The genome-wide DNA hypomethylation status estimated via LINE-1 methylation levels might be indicative of poor RFS in patients with HCC but not ICC or cHCC-CC. METHODS: We evaluated the level of LINE-1 methylation in 321 cases of curatively resected PLC {231 hepatocellular carcinoma (HCC), 19 combined hepatocellular and cholangiocarcinoma (cHCC-CC) and 71 intrahepatic cholangiocarcinoma (ICC)} via pyrosequencing of formalin-fixed paraffin-embedded (FFPE) tissues and examined its prognostic value.

Cystic gastric metastasis from pancreatic cancer.

Gastrointestinal tract metastasis from pancreatic cancer is quite rare. We present the case of a 58-year-old male patient who underwent distal pancreatectomy for pancreatic body cancer 5 years prior. Four years after the initial operation, a 15-mm cystic submucosal tumor was found in the antrum of the stomach. Because the tumor had grown to 25 mm and the level of carcinoembryonic antigen in the cystic fluid derived by ultrasound-guided fine-needle aspiration biopsy was high, partial resection of the stomach was performed 5 years after the distal pancreatectomy. Pathological diagnosis was gastric metastasis of pancreatic cancer. The patient has been alive without recurrence for 13 months after the resection of the cystic tumor. We are not aware of any similar cases of cystic gastric metastasis from pancreatic cancer published in the English literature.