Peripheral-dominant liver fibrosis and tumor distribution in a mouse model of congestive hepatopathy.

AIM: Congestive hepatopathy often leads to liver fibrosis and hepatocellular carcinoma. Imaging modalities provided clinical evidence that elevation of liver stiffness and tumor occurrence are mainly induced in the periphery of the liver in patients with congestive hepatopathy. However, clinical relevance of liver stiffness and liver fibrosis is unclear because liver congestion itself increases liver stiffness in congestive hepatopathy. It also unclear which factors configure such regional disparity of tumor development in patients with congestive hepatopathy. To answer these questions, we evaluated the macroscopic spatial distribution of liver fibrosis and tumors in the murine model of congestive hepatopathy. METHODS: Chronic liver congestion was induced by partial ligation of the suprahepatic inferior vena cava. Distribution of liver congestion, fibrosis, and tumors in partial ligation of the suprahepatic inferior vena cava mice were assessed by histological findings, laser microdissection (LMD)-based qPCR and enhanced computed tomography. LMD-based RNA-sequencing was performed to identify causal factors that promote tumor development in congestive hepatopathy. RESULTS: Liver fibrosis was mainly induced in the periphery of the liver and co-localized with distribution of liver congestion. Liver tumors were also induced in the periphery of the liver where liver congestion and fibrosis occurred. LMD-based RNA-sequencing revealed the upregulation of extracellular matrix/collagen fibril-, wound healing-, angiogenesis-, morphogenesis-, and cell motility-related signaling pathways in periphery of liver compared with liver center. CONCLUSIONS: Our findings showed the experimental relevance of liver congestion, fibrosis, and tumor development in congestive hepatopathy, and may provide important locational information. Macroscopic regional disparity observed in this murine model should be considered to manage patients with congestive hepatopathy.

Phase II trial of nafamostat mesilate/gemcitabin/S-1 for unresectable pancreatic cancer.

PURPOSE: To assess the efficacy of combination chemotherapy with nafamostat mesilate, gemcitabine and S-1 for unresectable pancreatic cancer patients. MATERIALS AND METHODS: The study was conducted as a single-arm, single center, institutional review board-approved phase II trial. Patients received nafamosntat mesilate (4.8 mg/kg continuous transregional arterial infusion) with gemcitabine (1000 mg/m2 transvenous) on days 1 and15, and with oral S-1 [(80 mg/day (BSA<1.25 m2), 100 mg/day (1.25 ≤ BSA<1.5 m2), or 120 mg/day (BSA ≥1.5 m2)] on days 1-14 or, days 1-7 and 15-21. This regimen was repeated at 28-day intervals. RESULTS: Forty-seven evaluable patients (Male/Female: 31/16, Age (median): 66 (range 35-78) yrs, Stage III/IV 10/37.) were candidates in this study. Two patients in stage III (20%) could undergo conversion surgery. Twenty-four patients (51%) underwent subsequent treatment (1st line/ 2nd line / 4th line, 13/ 10/ 1, FOLFIRINOX: 12, GEM/nab-PTX: 18, TAS-118: 3, chemoradiation with S-1: 2, GEM/Erlotinib: 1, nal-IRI: 1, surgery: 2). Median PFS and OS were 9.7 (95% CI, 8.9-14.7 mo) and 14.2 months (99% CI, 13.3-23.9 mo), respectively. Median PFS in stage IV patients was 9.2 months (95% CI, 8.4-12.0 mo). Median OS in patients without subsequent treatment was 10.8 months (95% CI, 9.1-13.8 mo). Median OS in patients with subsequent treatment was 19.3 months (95% CI, 18.9-31.9 mo). Grade 4 treatment-related hematological toxicities were encountered in 7 patients. Two patients developed grade 3 allergic reaction after 6 cycles or later. No febrile neutropenia has been observed. CONCLUSION: NAM/GEM/S-1 therapy is safe and could be promising option for unresectable pancreatic cancer, especially for stage IV cancer.

Sphingosine-1-phosphate promotes tumor development and liver fibrosis in mouse model of congestive hepatopathy.

BACKGROUND AND AIMS: Chronic liver congestion reflecting right-sided heart failure (RHF), Budd-Chiari syndrome, or Fontan-associated liver disease (FALD) is involved in liver fibrosis and HCC. However, molecular mechanisms of fibrosis and HCC in chronic liver congestion remain poorly understood. APPROACH AND RESULTS: Here, we first demonstrated that chronic liver congestion promoted HCC and metastatic liver tumor growth using murine model of chronic liver congestion by partial inferior vena cava ligation (pIVCL). As the initial step triggering HCC promotion and fibrosis, gut-derived lipopolysaccharide (LPS) appeared to induce LSECs capillarization in mice and in vitro. LSEC capillarization was also confirmed in patients with FALD. Mitogenic factor, sphingosine-1-phosphate (S1P), was increased in congestive liver and expression of sphingosine kinase 1, a major synthetase of S1P, was increased in capillarized LSECs after pIVCL. Inhibition of S1P receptor (S1PR) 1 (Ex26) and S1PR2 (JTE013) mitigated HCC development and liver fibrosis, respectively. Antimicrobial treatment lowered portal blood LPS concentration, LSEC capillarization, and liver S1P concentration accompanied by reduction of HCC development and fibrosis in the congestive liver. CONCLUSIONS: In conclusion, chronic liver congestion promotes HCC development and liver fibrosis by S1P production from LPS-induced capillarized LSECs. Careful treatment of both RHF and liver cancer might be necessary for patients with RHF with primary or metastatic liver cancer.

Analysis of risk factors for surgical site infection and postoperative recurrence following inguinal and femoral hernia surgery in adults.

OBJECTIVE: We aimed to evaluate the causes of complications following surgery for inguinal and femoral hernia, using surgical site infection (SSI) and recurrence rate as indicators of outcomes to consider appropriate treatments. METHODS: We retrospectively assessed the medical histories of 1,098 patients with adult inguinal and femoral hernias who underwent herniorrhaphy between July 2010 and March 2019. Using SSI and recurrence rate as indicators of outcomes, we statistically assessed the influence of preoperative and operative conditions on surgical outcomes. RESULTS: The occurrence of postoperative SSI was significantly more frequent in patients who experienced a long surgical duration, excessive blood loss, and incarceration; underwent emergency surgery and bowel resection; and in whom no mesh sheet insertion was performed. There was no correlation between mesh use and SSI in cases that did not require emergency incarceration repair. For cases involving hernia incarceration, the use of a mesh sheet was avoided to prevent potential infection, which could explain the high incidence of SSI in cases where mesh was not used. The hernia may have recurred due to technical issues during the procedure, as well as failure to ligate the hernia sac. CONCLUSIONS: Selecting the appropriate surgical method for hernia repair may reduce the incidence of SSI. If manual reduction of inguinal hernias is not possible, an appropriate surgical procedure should be determined based on laparoscopic findings in facilities where laparoscopic hernia surgeries are frequently performed. Moreover, in cases without infection and bowel resection, mesh use may be beneficial. Recurrence can be prevented by ligating the hernia sac during surgery and solving relevant technical problems.

Nafamostat mesilate, a nuclear factor kappa B inhibitor, enhances the antitumor action of radiotherapy on gallbladder cancer cells.

Nuclear factor kappa B (NF-κB) is a transcriptional factor that can be activated by radiotherapy and chemotherapy. The synthetic protease inhibitor nafamostat mesilate (NM) inhibits NF-κB activity and exerts antitumor actions in various types of cancer. In the present study, we hypothesized that NM might enhance the antitumor action of radiotherapy on gallbladder cancer (GBC) cells by inhibiting radiation-induced NF-κB activity. Thus, we investigated the correlation between radiotherapy and NF-κB activity in GBC cells. We assessed the in vitro effects of radiotherapy with or without NM on NF-κB activity, apoptosis of GBC cells (NOZ and OCUG-1), induction of apoptotic cascade, cell cycle progression, and viability of GBC cells using four treatment groups: 1) radiation (5 Gy) alone; 2) NM (80 µg/mL and 40 µg/mL, respectively) alone; 3) combination (radiation and NM); and 4) vehicle (control). The same experiments were performed in vivo using a xenograft GBC mouse model. In vitro, NM inhibited radiation-induced NF-κB activity. Combination treatment significantly attenuated cell viability and increased cell apoptosis and G2/M phase cell cycle arrest compared with those in the other groups for NOZ and OCUG-1 cells. Moreover, combination treatment upregulated the expression of apoptotic proteins compared with that after the other treatments. In vivo, NM improved the antitumor action of radiation and increased the population of Ki-67-positive cells. Overall, NM enhanced the antitumor action of radiotherapy on GBC cells by suppressing radiation-induced NF-κB activity. Thus, the combination of radiotherapy and NM may be useful for the treatment of locally advanced unresectable GBC.

Treatment of intrahepatic recurrence after hepatectomy for hepatocellular carcinoma.

BACKGROUND: Prognostic factors after treatment for intrahepatic recurrent hepatocellular carcinoma (RHCC) after hepatic resection (Hx) are controversial. The current study aimed to examine the impact of treatment modality on the prognosis of intrahepatic RHCC following Hx. METHODS: For control of variables, the subjects were 56 patients who underwent treatment for intrahepatic RHCC, three or fewer tumors, each measuring ≤3 cm in diameter without macroscopic vascular invasion (MVI), between 2000 and 2011. Retreatment consisted of repeat Hx (n = 23), local ablation therapy (n = 11) and transarterial chemoembolization or transcatheter arterial infusion (TACE/TAI) (n = 22). We retrospectively investigated the relation between type of treatment for RHCC and overall survival (OS) as well as disease-free survival (DFS). RESULTS: In multivariate (MV) analysis, the poor prognostic factors in DFS after retreatment consisted of disease-free interval (DFI) (≤1.5 y) (P = .011), type of retreatment (TACE/TAI) (P = .002), age (<65 y old) (P = .0022), perioperative RBC transfusion (P = .025), while those in OS after retreatment were DFI (≤1.5 y) (P < .0001). In evaluation of stratification for type of retreatment, DFS in the repeat Hx group was significantly better than those in the local ablation therapy group or the TACE/TAI group (P = .023 or P < .0001, respectively). CONCLUSIONS: DFI (≤1.5 y) was an independent poor prognostic factor in both DFS and OS, and repeat Hx for intrahepatic RHCC, few in number and size without MVI, seems to achieve the most reliable local control.

Suppression of lysosomal acid alpha-glucosidase impacts the modulation of transcription factor EB translocation in pancreatic cancer.

Lysosomal degradation plays a crucial role in the metabolism of biological macromolecules supplied by autophagy. The regulation of the autophagy-lysosome system, which contributes to intracellular homeostasis, chemoresistance, and tumor progression, has recently been revealed as a promising therapeutic approach for pancreatic cancer (PC). However, the details of lysosomal catabolic function in PC cells have not been fully elucidated. In this study, we show evidence that suppression of acid alpha-glucosidase (GAA), one of the lysosomal enzymes, improves chemosensitivity and exerts apoptotic effects on PC cells through the disturbance of expression of the transcription factor EB. The levels of lysosomal enzyme were elevated by gemcitabine in PC cells. In particular, the levels of GAA were responsive to gemcitabine in a dose-dependent and time-dependent manner. Small interfering RNA against the GAA gene (siGAA) suppressed cell proliferation and promoted apoptosis in gemcitabine-treated PC cells. In untreated PC cells, we observed accumulation of depolarized mitochondria. Gene therapy using adenoviral vectors carrying shRNA against the GAA gene increased the number of apoptotic cells and decreased the tumor growth in xenograft model mice. These results indicate that GAA is one of the key targets to improve the efficacy of gemcitabine and develop novel therapies for PC.

Phase II Study of Adjuvant Chemotherapy With Gemcitabine and Nafamostat Mesilate for Pancreatic Cancer.

OBJECTIVES: The aim of this study was to clarify the effectiveness of combination chemotherapy targeting gemcitabine (GEM)-induced nuclear factor kappa B as adjuvant therapy for pancreatic cancer. METHODS: Patients who were planned after curative surgery (residual tumor classification R0 or R1) for pancreatic cancer to receive six cycles of adjuvant chemotherapy of regional arterial infusion of nafamostat mesilate with GEM between June 2011 and April 2017 were enrolled in this single-center, institutional review board-approved phase II trial (UMIN000006163). The Kaplan-Meier method was used to estimate disease-free survival and overall survival. RESULTS: In 32 patients [male/female: 18/14; age: median, 65.5 years (range, 48-77 years); pathological stage (Union for International Cancer Control 8th): IA/IB/IIA/IIB/III, 2/2/9/18/1, respectively] who met the eligibility criteria, the median overall survival and disease-free survival were 36.4 months (95% confidence interval, 31.7-48.3) and 16.4 months (95% confidence interval, 14.3-22.0), respectively. Grade 4 treatment-related hematological toxicities were seen in 5 patients (15.6%) (all neutropenia). One patient developed grade 3 nonhematological toxicities (rash). CONCLUSIONS: Adjuvant chemotherapy with regional arterial infusion of nafamostat mesilate and GEM is safe and has potential as an option in adjuvant setting after curative surgery for pancreatic cancer.

Resection of liver metastasis from submandibular gland carcinoma five years after the primary operation: A case.

INTRODUCTION: Liver metastasis of submandibular gland carcinoma is not uncommon, yet its optimal management is still unclear. We report a case of resection of liver metastasis from submandibular gland carcinoma five years after the primary operation. CASE PRESENTATION: The patient was a 76-year-old male who had undergone resection of primary adenoid cystic carcinoma of the submandibular gland in 2012. On follow-up computed tomography (CT) five years after the initial operation, a tumor was found incidentally in hepatic segment 6. Magnetic resonance imaging (MRI) confirmed the lesion's presence. Based on imaging findings and medical history, the lesion was suspected to be a liver metastasis of the previous submandibular gland carcinoma. The patient underwent hepatic posterior sectionectomy. His postoperative course was uneventful except for minor bile leakage that subsided without surgical intervention, and he was discharged on postoperative day 25. Postoperative pathological examinations of the hepatic tumor showed exactly the same features seen in the primary submandibular gland carcinoma, and the diagnosis as metastasis from this carcinoma was confirmed. DISCUSSION: Liver resection may be a reasonable choice of treatment for liver metastasis of submandibular gland carcinoma. Further evidence from studies with larger patient populations must be accumulated to confirm this. CONCLUSION: We report our experience with a case of liver metastasis from submandibular gland carcinoma, which was resected five years after the primary operation.

Short- and long-term outcomes of laparoscopic versus open gastrectomy for locally advanced gastric cancer following neoadjuvant chemotherapy.

BACKGROUND: This study aimed to investigate the short- and long-term outcomes of laparoscopic gastrectomy (LG) in patients with advanced gastric cancer following neoadjuvant chemotherapy (NAC) to determine its safety and feasibility. METHODS: We retrospectively investigated 51 patients who underwent gastrectomy for locally advanced gastric cancer [cT3-4/N1-3 or macroscopic type 3 (> 80 mm) or type 4] following NAC between November 2009 and January 2018. After excluding two patients who underwent palliative surgery due to peritoneal dissemination, 49 patients were ultimately selected for this cohort study. The patients were then divided into the LG group and open gastrectomy (OG) group, after which the clinicopathological characteristics as well as short- and long-term outcomes were examined. RESULTS: Compared with the OG group, the LG group demonstrated a significantly lower amount of intraoperative blood loss and a shorter hospital stay. The overall complication rates were 10% (2 of 20 patients) and 24% (7 of 29 patients) in the LG and OG groups (P = 0.277), respectively. No significant differences in 5-year disease-free (LG 44.4% vs. OG 53.3%; P = 0.382) or overall survival rates (LG 46.9% vs. OG 54.0%; P = 0.422) were observed between the groups. Multivariate analysis revealed that the surgical procedure (LG vs. OG) was not an independent risk factor for disease-free (P = 0.645) or overall survival (P = 0.489). CONCLUSIONS: LG may be a potential therapeutic option for patients with gastric cancer following NAC considering its high success rates and acceptable short- and long-term outcomes.

The Prognostic Significance of C-reactive Protein-To-Lymphocyte Ratio in Colorectal Liver Metastases.

BACKGROUND: The preoperative systemic inflammation has been reported to predict tumor recurrence and survival in various cancers, including colorectal liver metastases (CRLM). However, more sensitive biomarker is required to improve perioperative management of CRLM. Therefore, we developed a novel indicator; C-reactive protein-to-lymphocyte ratio (CLR). The aim of this study is to evaluate the prognostic significance of CLR in patients with CRLM after hepatic resection. MATERIALS AND METHODS: The study comprised 197 patients who had undergone hepatic resection for CRLM between January 2000 and December 2018. We retrospectively investigated the relation between CLR and disease-free survival and overall survival after hepatic resection and compared their prognostic significance with that of the C-reactive protein-to-albumin ratio and neutrophil-to-lymphocyte ratio. RESULTS: Optimal cutoff level of the CLR by receiver operating characteristics analysis was 62.8 × 10-6. By multivariate analysis, CLR was an independent predictor of disease-free survival [hazard ratio (HR): 1.463, 95% confidence interval (CI): 1.003-2.135, P = 0.048), whereas lymph node metastases>4 (HR: 1.804, 95% CI: 1.100-2.958, P = 0.019) and CLR (HR: 1.656, 95% CI: 1.007-2.724, P = 0.047) were independent predictors of overall survival, while the C-reactive protein-to-albumin ratio and neutrophil-to-lymphocyte ratio were not. CONCLUSIONS: CLR may be an independent and significant indicator of poor long-term outcomes in patients with CRLM after hepatic resection.

Comparison of laparoscopic surgery and hand-assisted laparoscopic surgery in esophagectomy: A propensity score-matched analysis.

INTRODUCTION: Laparoscopic surgery (LAP) and hand-assisted laparoscopic surgery (HALS) for mobilization of the stomach and abdominal lymph node dissection in esophagectomy have become standard procedures in Japan. However, the differences in outcomes between LAP and HALS have not been examined. We aimed to compare the safety and feasibility of these techniques in patients undergoing esophagectomy. METHODS: We assessed 171 patients who underwent esophagectomy and reconstruction for clinical stage 0 to IVa esophageal cancer; 108 patients were treated with HALS and 63 with LAP. Mortality, morbidity, and long-term survival were compared in all patients who had undergone these surgical procedures and then in 59 propensity score-matched pairs to correct for differences in baseline characteristics. RESULTS: In our analysis, HALS had a shorter abdominal operative time (84.4 ± 26.6 vs 110.0 ± 34.1 minutes, P < .0001), but LAP enabled a larger number of abdominal lymph nodes to be harvested with (17.9 ± 6.6 vs 15.4 ± 7.4, P = .0486). The 5-year overall survival rates were 62.1% and 74.5% (P = .1257) for patients who had undergone HALS and LAP, respectively, and the relapse-free survival rates were 67.0% and 72.3% (P = .7243). CONCLUSIONS: There were no significant differences in postoperative mortality and morbidity between the two groups. This suggests that in addition to having a short operative time, HALS has good technical feasibility and is oncologically safe for patients with esophageal cancer.

Preoperative controlling nutritional status (CONUT) score predicts long-term outcomes in patients with non-B non-C hepatocellular carcinoma after curative hepatic resection.

PURPOSE: The controlling nutritional status (CONUT) score has been reported to predict outcomes in patients with hepatocellular carcinoma (HCC). However, the prognostic significance of the CONUT score in patients with non-B non-C (NBNC) HCC remains to be established. METHODS: The study comprised 246 patients who had undergone elective hepatic resection for HCC between April 2003 and October 2017. We retrospectively investigated the relation between preoperative CONUT score as well as clinicopathological characteristics and disease-free survival (DFS) as well as overall survival (OS). RESULTS: In univariate analyses, CONUT score was associated with DFS and OS in patients with NBNC-HCC (p ≤ 0.01), while there was no significant association of CONUT score with DFS and OS in patients with HBV- and HCV-related HCC (p ≥ 0.1). Of the 111 patients with NBNC-HCC, 97 (87.4%) had CONUT score ≤ 3 (low CONUT score) and the other 14 (12.6%) had CONUT score ≥ 4 (high CONUT score). In the patients with NBNC-HCC, multivariate analysis identified age ≥ 65 years (p = 0.03), multiple tumors (p < 0.01), and high CONUT score (p = 0.03) as the independent and significant predictors of DFS, while multiple tumors (p = 0.01), microvascular invasion (p < 0.01), and high CONUT score (p = 0.01) were the independent and significant predictors of OS. CONCLUSIONS: The CONUT score seems to be a reliable and independent predictor of both DFS and OS after hepatic resection for NBNC-HCC.

The segment IV approach: a useful method for achieving the critical view of safety during laparoscopic cholecystectomy in patients with anomalous bile duct.

BACKGROUND: The critical view of safety (CVS) method can be achieved by avoiding vasculo-biliary injury resulting from misidentification during laparoscopic cholecystectomy (LC). Although achieving the CVS has become popular worldwide, there is no established standardized technique to achieve the CVS in patients with an anomalous bile duct (ABD). We recently reported our original approach for securing the CVS using a new landmark, the diagonal line of the segment IV of the liver (D-line). The D-line is an imaginary line that lies on the right border of the hilar plate. The cystic structure can be securely isolated along the D-line without any misidentification, regardless of the existence of an ABD. We named this approach the segment IV approach in LC. METHODS: In this study, we adopted the segment IV approach in patients with an ABD. RESULTS: From October 2015 to June 2020, 209 patients underwent LC using the segment IV approach. Among them, three (1.4%) were preoperatively diagnosed with an ABD. The branching point of the cystic duct was the posterior sectional duct, anterior sectional duct, or left hepatic duct in each patient. The CVS was achieved in all cases without any complications. CONCLUSION: It is a promising technique, especially even for patients with an ABD during LC.

Five-year Outcomes of Chemotherapy With Docetaxel, Cisplatin, and 5-Fluorouracil Followed by Oesophagectomy in Oesophageal Cancer.

BACKGROUND: Preoperative chemotherapy with surgery is the most effective treatment modality in Japan for advanced oesophageal squamous cell carcinoma (OSCC). We evaluated the long-term outcomes associated with preoperative docetaxel/cisplatin/5-fluorouracil (DCF) administration followed by oesophagectomy in OSCC. PATIENTS AND METHODS: Overall, 76 consecutive patients with cStage IB-IIIC OSCC were enrolled. After two cycles of preoperative DCF, oesophagectomy was performed. Survival monitoring was performed and relevant risk factors were analysed. RESULTS: The median follow-up period was 88.3 months. The 5-year overall and recurrence-free survival rates were 51% and 43%, respectively. In the multivariable analysis, cT3 stage [hazard ratio (HR)=1.81, 95% confidence interval (CI)=1.08-6.16], incomplete chemotherapy (HR=2.35, 95% CI=1.37-4.02), poor clinical response (HR=1.82, 95% CI=1.01-3.29), and postoperative complications (HR=2.11, 95% CI=1.14-3.90) were independent predictors of poorer overall survival. CONCLUSION: The 5-year outcomes of preoperative DCF with oesophagectomy were favourable. Our findings can aid in the formulation of strategies aimed at improving prognosis in OSCC.

De novo hepatocellular carcinoma in living donor liver grafts: A Japanese multicenter experience.

AIM: Direct-acting antivirals for hepatitis C virus have reduced the decompensation risk. Immunosuppressants for transplantation raise the risk of occurrence of de novo malignancies. We assessed the probabilities of and risk factors for de novo hepatocellular carcinoma (HCC) development post-living donor liver transplantation (LDLT). METHODS: We retrospectively evaluated the data of developed HCC in a graft including metastatic HCC post-LDLT from 2779 adult cases collected from nine major liver transplantation centers in Japan. RESULTS: Of 2779 LDLT adult recipients, 34 (1.2%) developed HCCs in their grafts. Of 34, five HCCs appeared to be de novo because of a longer period to tumor detection (9.7 [6.4-15.4] years) and no HCC within the native liver of the two recipients. The donor origin of three of five de novo HCCs was confirmed using microsatellite analysis in resected tissue. Primary disease of all five was hepatitis C virus-related cirrhosis, of which two were treated with direct-acting antivirals. Four of five developed HCC de novo in the hepatitis B core antibody-positive grafts. De novo HCCs had favorable prognosis; four of five were cured with complete remission. However, recurrent HCC (n = 29) in the graft had a poorer outcome, especially in patients with neutrophil to lymphocyte ratio scores above 4 (median survival time, 262 [19-463] days). CONCLUSION: Analysis of the database from major liver transplantation institutes in Japan revealed that de novo HCCs determined by microsatellite analysis were rarely detected, but the majority were successfully treated. LDLT recipients with higher risks of de novo HCC, including those with hepatitis B core antibody-positive grafts, should be carefully followed by surveillance of the liver graft.

Multidisciplinary treatment for colorectal liver metastases in elderly patients.

BACKGROUND: Limited data describe the therapeutic practice and outcomes of colorectal liver metastases (CRLMs) in elderly patients. We aimed to evaluate the impact of age on multidisciplinary treatment for CRLMs. METHODS: We reviewed treatment and outcomes for patients in different age groups who underwent initial hepatectomy for CRLMs from 2004 through 2012. RESULTS: We studied 462 patients who were divided into three groups by age: ≤ 64 years (n = 265), 65-74 years (n = 151), and ≥ 75 years (n = 46). The rate of major hepatectomy and incidence of postoperative complications did not differ between groups. Adjuvant chemotherapy was used less in the ≥ 75-year group (19.6%) than that in the ≤ 64 (54.3%) or 65-74 age group (43.5%). Repeat hepatectomy for liver recurrence was performed less in the ≥ 75-year group (35%) than in the ≤ 64 (57%) or 65-74 (66%) age group. The 5-year disease-specific survival (DSS) rate of 44.2% in the ≥ 75-year group was lower than in the ≤ 64 (59.0%) or 65-74 (64.7%) age group. Multivariate analysis revealed age ≥ 75 years was an independent predictor of poor DSS. CONCLUSIONS: Liver resection for CRLMs can be performed safely in elderly patients. However, repeat resection for recurrence are performed less frequently in the elderly, which may lead to the poorer disease-specific prognosis.

A successfully treated case of Lemmel syndrome with pancreaticobiliary maljunction: A case report.

BACKGROUND: Lemmel syndrome is a rare condition that leads to cholangitis and/or pancreatitis due to intraduodenal diverticulum. Surgery is considered for the treatment of severe or repeated symptoms in patients with this condition. CASE PRESENTATION: An 81-year-old woman was admitted to our hospital, complaining of general fatigue, BT 38.8 degree, and right hypochondoralgia. Her hepatobiliary enzyme levels were elevated, and enhanced abdominal computed tomography revealed dilation of the common bile duct and intraduodenal diverticulum. After restarting oral intake, her symptoms were exacerbated. Endoscopic retrograde cholangio-pancreatography (ERCP) revealed pancreaticobiliary maljunction and parapapillary diverticulum. Under a diagnosis of Lemmel syndrome with pancreaticobiliary maljunction complicated by acute pancreatitis and cholangitis, we performed extrahepatic bile duct resection with cholecystectomy and papilloplasty. Her postoperative course was uneventful, and the patient was discharged 20 days after surgery. She remains well at 5 months after surgery. CONCLUSION: We herein report a successfully diagnosed and treated case of Lemmel syndrome with pancreaticobiliary maljunction.

Six autoantibodies as potential serum biomarkers of hepatocellular carcinoma: A prospective multicenter study.

Serum autoantibodies have been reported to react with tumor-associated antigen (TAA) in various cancers. This multicenter study evaluated the diagnostic and prognostic value of six autoantibodies against a panel of six hepatocellular carcinoma (HCC)-associated antigens, including Sui1, p62, RalA, p53, NY-ESO-1 and c-myc. A total of 160 patients with HCC and 74 healthy controls were prospectively enrolled from six institutions. Serum antibody titers were determined by enzyme-linked immunosorbent assays. The sensitivities were 19% for Sui1, 18% for p62, 17% for RalA, 11% for p53, 10% for NY-ESO-1 and 9% for c-myc. Overall sensitivity of the TAA panel (56%) was higher than that of α-fetoprotein (41%, P < .05). The combined sensitivity of the TAA panel and α-fetoprotein was significantly higher than that of α-fetoprotein alone (P < .001). The difference in overall survival of TAA panel-positive and panel-negative patients was significant when the Stage I/II patients were combined (P = .023). Overall survival was worse in NY-ESO-1 antibody-positive than in NY-ESO-1 antibody-negative patients (P = .002). Multivariate analysis found that positivity for the TAA panel was independently associated with poor prognosis (P = .030). This TAA panel may have diagnostic and prognostic value in the patients with HCC.

Correction to: Signification of Systemic Immune-Inflammation Index for prediction of prognosis after resecting in patients with colorectal cancer.

The authors regrets that there is a typo error on Tables 1, 2 and 3 of their published paper.