Tranexamic acid and blood loss in pancreaticoduodenectomy: TAC-PD randomized clinical trial.

BACKGROUND: Tranexamic acid (TXA) may reduce intraoperative blood loss, but it has not been investigated in pancreaticoduodenectomy (PD). METHODS: A pragmatic, multicentre, randomized, blinded, placebo-controlled trial was conducted. Adult patients undergoing planned PD for biliary, duodenal, or pancreatic diseases were randomly assigned to TXA or placebo groups. Patients in the TXA group were administered 1 g TXA before incision, followed by a maintenance infusion of 125 mg/h TXA. Patients in the placebo group were administered the same volume of saline as those in the placebo group. The primary outcome was blood loss during PD. The secondary outcomes included perioperative blood transfusions, operating time, morbidity, and mortality. RESULTS: Between September 2019 and May 2021, 218 patients were randomly assigned and underwent surgery (108 in the TXA group and 110 in the placebo group). Mean intraoperative blood loss was 659 ml in the TXA group and 701 ml in the placebo group (mean difference -42 ml, 95 per cent c.i. -191 to 106). Of the 218 patients, 202 received the intervention and underwent PD, and the mean blood loss during PD was 667 ml in the TXA group and 744 ml in the placebo group (mean difference -77 ml, 95 per cent c.i. -226 to 72). The secondary outcomes were comparable between the two groups. CONCLUSION: Perioperative TXA use did not reduce blood loss during PD. REGISTRATION NUMBER: jRCTs041190062 (https://jrct.niph.go.jp).

Removing part of the pancreas is an operation with a risk of major blood loss. Tranexamic acid is a drug thought to reduce blood loss. This study asked the question, 'Does tranexamic acid reduce blood loss during surgery on the pancreas?' Half of patients received tranexamic acid during surgery. The other half received only standard care. This study showed that tranexamic acid did not decrease the blood loss during the surgery and may have little effect in patients having a pancreaticoduodenectomy.

Correlation between the complex of small heat shock proteins (HSPBs) and the progression in patients with hepatocellular carcinoma.

Small heat shock proteins (HSPBs) regulate various cell functions. We previously reported that HSPB1, HSPB6, and HSPB8 each suppress the progression of hepatocellular carcinoma (HCC). The heterooligomerization of HSPs is speculated to be crucial for functional activities. Here, we investigated the relationship between the complex of HSPBs and the progression of HCC. HSPB1/HSPB6 complex and HSPB1/HSPB8 complex, but not HSPB6/HSPB8 complex, were observed in both HSPB6-overexpressing human HCC-derived HuH-7 cells and resected human HCC tumor tissue. Differentiation, stage, tumor size, and vein invasion of HCC were inversely related to the presence of HSPB complexes in the HCC tissue. Our results strongly suggest that the HSPB complex formation plays a suppressive role in the HCC progression.

Identification of the suitable candidates for EOB-MRI with the high risk of the presence of non-hypervascular hypointense nodules in patients with HCV infection.

OBJECTIVES: Non-hypervascular hypointense nodules (NHHNs) depicted by gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) have a high likelihood of progressing to hepatocellular carcinoma (HCC). The presence of NHHNs is a strong risk factor for HCC development in patients with chronic hepatitis C virus (HCV) infection after the achievement of sustained virologic response (SVR). However, it is difficult for all patients with HCV infection to undergo EOB-MRI for NHHN detection. We therefore explored serum markers that potentially indicate the presence of NHHNs. METHODS: Three serum markers, alpha-fetoprotein (AFP), FIB-4 index, and Wisteria floribunda agglutinin-positive Mac-2 binding protein glycan isomer (M2BPGi), were measured in 481 patients with HCV infection and no history of HCC who underwent EOB-MRI. The associations between these serum marker levels and the presence of NHHNs were investigated. RESULTS: All three markers were associated with the presence of NHHNs. M2BPGi predicted the presence of NHHNs more accurately than AFP and FBB-4 index; M2BPGi had the highest area under the receiver operating characteristic curve. Multivariate analysis identified male gender and high M2BPGi as factors associated with the presence of NHHNs. When patients were stratified by the degree of liver fibrosis, M2BPGi increased with the progression of fibrosis. In addition, NHHNs were more prevalently detected in patients with higher M2BPGi (COI > 3.46) in patients with similar fibrosis degree. CONCLUSIONS: M2BPGi is a serum marker that potentially identifies HCV patients with high risk of the presence of NHHNs, for whom EOB-MRI should be considered. KEY POINTS: • Non-hypervascular hypointense nodule on EOB-DTPA-enhanced MRI is pre-HCC nodule with high likelihood of progressing to HCC, which is a strong predictor for HCC that develops after the eradication of HCV in patients with HCV infection. • It is difficult for all patients with HCV infection to undergo EOB-MRI for NHHN detection due to limited access, limited availability of MRI equipment, and high costs. • Serum Wisteria floribunda agglutinin-positive Mac-2 binding protein glycan isomer (M2BPGi) levels effectively indicate the presence of NHHNs and can be used to identify patients with high risk of their presence, for whom EOB-DTPA-enhanced MRI should be considered.

Outcome of Hepatocellular Carcinoma Detected During Surveillance: Comparing USA and Japan.

BACKGROUND & AIMS: Differences in outcomes of hepatocellular carcinoma (HCC) between countries have been largely attributed to variation in the conduct of surveillance and subsequent HCC treatment eligibility. However, differences in outcomes among those detected under surveillance have not been well described. We compared characteristics and prognosis between patients with surveillance-detected HCC from the United States (US) and Japan. METHODS: Patients in whom initial HCC was detected under surveillance between January 2006 and December 2015 from two centers in the US and two from Japan were included. Survival was compared between patients from the US and Japan using multivariable Cox regression analysis and propensity-score matched analysis. We performed subgroup analyses by liver disease etiology, tumor stage, and type of HCC treatment. RESULTS: Of 3788 HCC patients, 1797 (47.4%) were diagnosed under surveillance, 715 from the US and 1082 from Japan. Patients from the US diagnosed under surveillance had worse liver dysfunction and larger tumor burden than those from Japan. In multivariate analysis, US patients with surveillance-detected HCC had significantly worse survival than those from Japan (HR 1.17, 95% CI 1.00-1.35), which was also observed in propensity-score matched analysis. However, this difference was no longer significant after adjusting for treatment type (HR 1.07, 95% CI 0.92-1.25). When stratified by treatment type, survival was comparable between the two countries except lower survival among patients who underwent resection in the US versus Japan. CONCLUSIONS: Prognosis of patients with surveillance-detected HCC is poorer in the US than Japan, primarily driven by differences in treatment delivery. Studies are necessary to elucidate reasons for these differences.

Prediction of early recurrence of hepatocellular carcinoma after resection using digital pathology images assessed by machine learning.

Hepatocellular carcinoma (HCC) is a representative primary liver cancer caused by long-term and repetitive liver injury. Surgical resection is generally selected as the radical cure treatment. Because the early recurrence of HCC after resection is associated with low overall survival, the prediction of recurrence after resection is clinically important. However, the pathological characteristics of the early recurrence of HCC have not yet been elucidated. We attempted to predict the early recurrence of HCC after resection based on digital pathologic images of hematoxylin and eosin-stained specimens and machine learning applying a support vector machine (SVM). The 158 HCC patients meeting the Milan criteria who underwent surgical resection were included in this study. The patients were categorized into three groups: Group I, patients with HCC recurrence within 1 year after resection (16 for training and 23 for test); Group II, patients with HCC recurrence between 1 and 2 years after resection (22 and 28); and Group III, patients with no HCC recurrence within 4 years after resection (31 and 38). The SVM-based prediction method separated the three groups with 89.9% (80/89) accuracy. Prediction of Groups I was consistent for all cases, while Group II was predicted to be Group III in one case, and Group III was predicted to be Group II in 8 cases. The use of digital pathology and machine learning could be used for highly accurate prediction of HCC recurrence after surgical resection, especially that for early recurrence. Currently, in most cases after HCC resection, regular blood tests and diagnostic imaging are used for follow-up observation; however, the use of digital pathology coupled with machine learning offers potential as a method for objective postoprative follow-up observation.

Short- and Long-Term Outcomes of Transabdominal Preperitoneal, Open Mesh Plug and Open Tissue Inguinal Hernia Repair.

BACKGROUND: There have been few comparisons of the postoperative outcomes of transabdominal preperitoneal (TAPP), open mesh plug (mesh plug) and open tissue (tissue) hernia repair. The objectives of this study were to compare these repair methods. METHODS: This was a retrospective study of 1813 inguinal hernia patients between January 2008 and December 2016. Of these patients, 474 underwent TAPP repair, 1293 underwent mesh plug repair, and 46 underwent tissue repair. The short-term and long-term outcomes determined by questionnaire were compared among the three groups. In addition, risk factors for patient dissatisfaction were assessed. RESULTS: In the TAPP group, the postoperative complications rate was the lowest at 4.6% (7.4% and 6.5% in the mesh plug and the tissue groups, respectively, P = 0.07), and recurrence rate was lower compared to the mesh plug group (0.8% vs. 3.3%, P = 0.002). As long-term outcomes, 92%, 88% and 75% of patients were satisfied in the TAPP, mesh plug and tissue groups, respectively (P = 0.03). The rate of patients with numbness was 3.1% in the TAPP group, 5.2% in the mesh plug group and 14% in the tissue group (P = 0.04). Predictive independent risk factors for patient dissatisfaction were complications (OR: 3.99, 95% CI: 1.35-11.8, P = 0.012) and infection (OR: 16.9, 95% CI: 1.25-229, P = 0.003). CONCLUSIONS: TAPP repair is superior to mesh plug and tissue repairs in terms of complications, satisfaction and numbness, as determined by questionnaire. Complications and infection were independently associated with the patient dissatisfaction.

Liver Resection for Multiple Hepatocellular Carcinomas: A Japanese Nationwide Survey.

OBJECTIVE: The aim of the study was to evaluate the survival benefits of liver resection (LR) compared with transarterial chemoembolization (TACE) for patients with multiple hepatocellular carcinomas (HCCs). BACKGROUND: Despite significant improvements in diagnostic imaging and the widespread application of screening programs, some patients with HCC continue to present with multiple tumors. The surgical indications for multiple HCCs remain controversial. METHODS: Among 77,268 patients with HCC reported in a Japanese nationwide survey, 27,164 patients had multiple HCCs. The exclusion criteria were Child-Pugh B/C, treatment other than LR and TACE, >3 tumors, and insufficient available data. Ultimately, 3246 patients (LR: n = 1944, TACE: n = 1302) were included. The survival benefit of LR for patients multiple HCCs was evaluated by using propensity score matching analysis. RESULTS: The study group of 2178 patients (LR: n = 1089, TACE: n = 1089) seemed to be well matched. The overall survival rate in the LR group was 60.0% at 5 years, which was higher than that in the TACE group (41.6%, P < 0.001). Among patients with a tumor size of 30 mm or more, LR showed a survival benefit over TACE at 5 years (53.0% vs 32.7%, P < 0.001). The multivariate analysis indicated that age, serum albumin level, serum alpha-fetoprotein (AFP) level, macrovascular invasion, tumor size, and TACE were independent predictors of poor prognosis in multiple HCCs. CONCLUSIONS: LR could offer better long-term survival than TACE for patients with multiple HCCs (up to 3 tumors). If patients have good liver function (Child-Pugh A), LR is recommended, even for those with multiple HCCs with tumor sizes of 30 mm or more.

Phase 2 Trial of Adjuvant Chemotherapy With S - 1 for Node-Positive Biliary Tract Cancer (N-SOG 09).

BACKGROUND: Nodal metastasis is a leading attributable factor of poor survival in biliary tract cancer (BTC), and adjuvant chemotherapy targeting this high-risk feature has not been attempted to date. This study aimed to test the efficacy of adjuvant S - 1 for patients with node-positive BTC. METHODS: This single-arm multicenter phase 2 trial enrolled patients who underwent resection for histologically proven node-positive BTC. In this trial, S - 1 was administered at a dose of 80-120 mg/day on 14 days of a tri-weekly cycle for 6 months. The primary end point of the trial was 3-year overall survival (OS), in which the result would be promising if the 90% confidence interval (CI) surpassed a threshold of 30% (alpha error, 0.1; beta error, 0.2). The secondary end points were relapse-free survival (RFS), feasibility, and toxicity. RESULTS: The trial included 50 patients with perihilar (n = 23) or distal (n = 20) cholangiocarcinoma, or gallbladder cancer (n = 7). The median numbers of positive lymph nodes and examined lymph nodes were respectively 2 and 15. The 3-year OS and RFS were respectively 50% (90% CI, 40.9-59.1%) and 32.0% (95% CI, 19.1-44.9%), with median survival times of 34.6 months (95% CI, 19.3-49.8 months) and 18.4 months (95% CI, 11.9-24.9 months). Although hematologic toxicity often occurred, grades 3 and 4 toxicity were rare. The completion rate of the test therapy was 64%, and the median relative dose intensity was 87.5% (interquartile range, 50-100%). CONCLUSION: Adjuvant chemotherapy with S - 1 may be promising for patients with node-positive BTC.

Lower bile duct metastasis from rectal cancer after surgery for liver metastasis and intrahepatic bile duct metastasis: a case report.

BACKGROUND: Biliary metastasis of colorectal cancer is a manifestation of metastatic liver carcinoma, and is often difficult to differentiate from cholangiocarcinoma. Further, lower bile duct metastasis of colorectal cancer is rare. We report the case of a 74-year-old woman who underwent pylorus-preserving pancreatoduodenectomy for lower bile duct metastasis of rectal cancer. CASE PRESENTATION: The patient had undergone laparoscopic low anterior resection for rectal cancer (pT3N0M0 stage IIA) 6 years ago, laparoscopic anterior liver resection for liver metastasis (Couinaud segment V) 3 years ago, and left and caudal lobectomy with extrahepatic bile duct resection for left intrahepatic bile duct metastasis 6 months ago. A follow-up examination showed a 15 mm mass in the common bile duct, for which she underwent pylorus-preserving pancreatoduodenectomy. Histological and immunohistological examination of the specimens revealed similar cytokeratin (CK) expression patterns, which were negative for CK7 and positive for CK20. Therefore, the definitive diagnosis was metastasis from rectal cancer. CONCLUSIONS: In summary, we encountered a case of lower bile duct metastasis from rectal cancer, which is often difficult to differentiate from cholangiocarcinoma. In such patients, CK7 and CK20 expression patterns are important in differentiating the two. The mechanism of metastasis in this case was considered to be through cancer cell implantation from lymphatic spread, or through distant metastasis of the primary cancer.

Phase III randomised trial comparing 6 vs. 12-month of capecitabine as adjuvant chemotherapy for patients with stage III colon cancer: final results of the JFMC37-0801 study.

BACKGROUND: Up to 6-months oxaliplatin-containing regimen is now widely accepted as a standard adjuvant chemotherapy for stage III colorectal cancer (CRC). However, oral fluoropyrimidine monotherapy is used for some part of patients, especially in Asian countries including Japan, and its optimal duration is yet to be fully investigated. METHODS: A total of 1306 patients with curatively-resected stage III CRC were randomly assigned to receive capecitabine (2500 mg/m2/day) for 14 out of 21 days for 6 (n = 654) or 12 (n = 650) months. The primary endpoint was disease-free survival (DFS), and the secondary endpoints were relapse-free survival (RFS), overall survival (OS), and adverse events. RESULTS: The 3- and 5-year DFS were 70.0% and 65.3% in the 6M group and 75.3% and 68.7% in the 12M group, respectively (p = 0.0549, HR = 0.858, 90% CI: 0.732-1.004). The 5-year RFS was 69.3% and 74.1% in the 6M and 12M groups, respectively (p = 0.0143, HR = 0.796, 90% CI: 0.670-0.945). The 5-year OS was 83.2% and 87.6%, respectively (p = 0.0124, HR = 0.727, 90% CI: 0.575-0.919). The incidence of overall grade 3-4 adverse events was almost comparable in both groups. CONCLUSIONS: Although 12-month adjuvant capecitabine did not demonstrate superior DFS to that of 6-month, the observed better RFS and OS in the 12-month treatment period could be of value in selected cases.

Circulating microRNA-1246 as a possible biomarker for early tumor recurrence of hepatocellular carcinoma.

AIMS: Early tumor recurrence (ETR) after hepatic resection is a crucial predictor of poor prognosis in patients with hepatocellular carcinoma (HCC). The aim of this study was to identify clinically significant serum microRNAs (miRNAs) involved in the ETR of HCC. METHODS: We compared expression profiles of circulating miRNAs from serum samples between five HCC patients with ETR (recurrence within 12 months after hepatectomy) and five HCC patients without recurrence using microarray analysis of miRNA. The identified miRNA associated with ETR was further verified in 121 HCC patients, 73 liver disease patients, and 15 health controls by real-time quantitative reverse transcription-polymerase chain reaction (PCR). RESULTS: Of the approximately 2000 miRNAs analyzed, we identified 15 miRNAs for which expression levels correlated significantly with ETR. Of these miRNAs, we further investigated expression of miRNA-1246 (miR-1246). Quantitative PCR confirmed that miR-1246 was upregulated in HCC with ETR, compared to the level in HCC without ETR (P < 0.001). Serum miR-1246 showed a receiver operating characteristic curve area of 0.762, with 77.4% specificity and 54.1% sensitivity in discriminating HCC patients with ETR from HCC patients without ETR. Altered expression of miR-1246 was associated with aggressive tumor characteristics, including tumor-node-metastasis classification (P = 0.0413), tumor differentiation (P = 0.0419), and portal vein invasion (P = 0.0394). Moreover, multivariate Cox regression analysis identified serum miR-1246 level as an independent risk factor for overall survival (hazard ratio, 2.784; 95% confidence interval, 1.528-5.071; P = 0.0008). CONCLUSION: Circulating miR-1246 in serum has strong potential as a novel ETR and prognostic biomarker for HCC.

Comparison of end-to-end anastomosis and interposition graft during pancreatoduodenectomy with portal vein reconstruction for pancreatic ductal adenocarcinoma.

PURPOSE: Many studies report that pancreatoduodenectomy (PD) with portal-superior mesenteric vein resection and reconstruction (PVR) is not a contraindication to extended tumor resection for pancreatic ductal adenocarcinoma. However, the clinical benefit of an interposition graft for PVR still remains controversial. METHODS: Between January 2001 and December 2017, 199 patients with pancreatic cancer underwent PD either with or without PVR, and their medical records were reviewed retrospectively, paying specific attention to the PVR methods and the long-term outcome. RESULTS: Among the 122 patients with PVR, 97 (79.5%) underwent end-to-end anastomosis and 25 (20.5%) had an interposition graft using the right external iliac vein (REIV). The 2-year and 5-year survival rates of the no-PVR group (54.2% and 30.8%, respectively) were longer than both the end-to-end anastomosis group (24.5% and 13.7%) and the interposition graft group (32% and 10.0%) (p < 0.001). However, there was no significant difference in the survival between the end-to-end anastomosis group and the interposition graft group (p = 0.963). A multivariate analysis indicated that the level of preoperative serum albumin < 3.5 g/dL (risk ratio (RR) 2.08, 95% confidence interval (CI) 1.26 to 3.43; p = 0.004), and postoperative adjuvant chemotherapy (RR 1.82, 95% CI 1.19 to 2.79; p = 0.006) were independently associated with overall survival after PVR. CONCLUSIONS: An interposition graft using the REIV for PVR following PD is safe and effective. There was no significant prognostic difference between PD with end-to-end anastomosis and with an interposition graft in patients with pancreatic ductal adenocarcinoma.

Neoadjuvant CAPOX and bevacizumab alone for locally advanced rectal cancer: long-term results from the N-SOG 03 trial.

BACKGROUND: Neoadjuvant chemotherapy (NAC) alone for locally advanced rectal cancer (LARC) remains an experimental treatment, and the efficacy in terms of long-term outcome has not been fully elucidated. The N-SOG 03 trial examined the safety and efficacy of neoadjuvant CAPOX and bevacizumab (Bev) without radiotherapy in patients with poor-risk LARC. METHODS: Thirty-two patients with MRI-defined LARC received neoadjuvant CAPOX and Bev followed by curative resection between 2010 and 2011. The overall survival (OS), progression-free survival (PFS), and local-relapse rate (LRR) were calculated using the Kaplan-Meier method, and the risk factors were evaluated by multivariate analysis using the Cox proportional hazard models. This trial is registered with UMIN, number 000003507. RESULTS: In the entire cohort, the 5-year OS was 81.3%. Because of disease progression during chemotherapy, 3 patients ultimately did not undergo curative surgery. As a result, 29 patients underwent R0/1 resection. Among these 29 patients, the 5-year OS, PFS, and LRR were 89.7%, 72.4% and 13.9%, respectively. In multivariate analysis, cT4b tumor was an independent poor prognostic factor for OS and LRR, and ypT4b tumor and absence of N down-staging were independent poor prognostic factors for PFS. CONCLUSIONS: Patients with cT4b tumor were not suitable for NAC alone. However, the long-term outcomes of the other patients were satisfactory, and NAC alone might be an option for treatment of LARC. N down-staging was likely to bring favorable PFS, even in patients with cStage III.

Adverse oncological outcome of surgical site infection after liver resection for colorectal liver metastases.

PURPOSES: Postoperative complications are associated with poor overall and cancer-specific survival after resection of various types of cancer, including primary colorectal cancer. However, the oncological impact of surgical site infection (SSI) after liver resection for colorectal liver metastases (CLM) is unclear. The aim of this study was to investigate the oncological impact of SSI after liver resection for CLM. METHODS: We reviewed data from 367 consecutive patients treated by curative liver resection for CLM between 1994 and 2015. Patients who underwent simultaneous resection of colorectal cancer and synchronous liver metastases (n = 86) were excluded from the analysis. Short- and long-term outcomes were analyzed. RESULTS: SSI developed in 18 (6.4%) of the 281 patients in the analytic cohort (SSI group). The remaining 93.6% (n = 263) did not suffer this complication (no-SSI group). The operative duration was significantly longer in the SSI group than in the No-SSI group (p = 0.002). The overall survival rates 5 years after liver resection for CLM were 33.3% in the SSI group vs. 50.7% in the No-SSI group (p = 0.043). Multivariate analysis indicated that a liver tumor size ≥ 5 cm, R1 resection, and SSI were independently associated with overall survival after liver resection. CONCLUSIONS: SSI after liver resection for CLM is associated with adverse oncological outcomes.

The Prognostic Impact of the Lymphocyte-to-Monocyte Ratio in Resected Pancreatic Head Adenocarcinoma.

OBJECTIVE: Although the prognostic significance of systematic inflammation-based scores, such as the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), and the prognostic nutritional index (PNI), has been explored in pancreatic cancers, few reports have investigated the lymphocyte-to-monocyte ratio (LMR). We aimed to retrospectively investigate the prognostic value of the preoperative LMR in patients with resectable pancreatic head cancer (PHC). METHODS: From 2005 to 2016, 165 patients underwent pancreatoduodenectomy for PHC. All samples of peripheral blood were collected within 2 weeks prior to surgery. The best cutoff values of the LMR for predicting survival were determined by using a minimum p value approach (cut-off value: 2.8). The clinicopathological features of LMR <2.8 (n = 25) and ≥2.8 (n = 140) were compared. RESULTS: Patients with LMR ≥2.8 showed significantly lower NLR and PLR, and significantly higher PNI. Levels of CEA and CA19-9 were similar, and the pathological findings were comparable between the groups. The overall survival of patients with LMR ≥2.8 (66.2% at 1 year) was superior to that of patients with LMR <2.8 (36.1% at 1 year, p = 0.015). Multivariate analysis identified LMR <2.8 (hazard ratio 1.72, 95% CI 1.02-2.89, p = 0.042), lymphatic and venous invasion and positive surgical margin as independent prognostic factors. CONCLUSIONS: LMR may carry important prognostic information for patients with resectable PHC. Preoperative LMR may be considered for use in risk stratification for individual patients with PHC.

[Case of papillary cholangiocarcinoma with curative resection after long-term follow-up].

An asymptomatic 78-year-old woman with anemia had undergone abdominal ultrasonography 6 years ago, which revealed a 7-cm hepatic tumor. The patient was regularly followed-up assuming that the tumor was a hepatic hemangioma with cyst. However, the tumor gradually increased in size. Abdominal CT and MRI revealed that the tumor comprised a mixture of cystic and solid components, and there was dilation of the bile duct. A clinical diagnosis of intraductal papillary neoplasm of the bile duct was made. Caudate and right hepatic lobectomy was performed. The pathological diagnosis of the tumor was a papillary adenocarcinoma. This case, in which the patient was followed for 6 years before curative surgical treatment, is significant, because it demonstrates the slow-growing nature of this tumor.

Clinical Effect of Water-Soluble Contrast Agents for Small Bowel Obstruction in the Virgin Abdomen.

BACKGROUND: Several studies have investigated the diagnostic and therapeutic role of water-soluble contrast agents (WSCAs) in adhesive small bowel obstruction (SBO). However, the clinical effect of WSCA for SBO without previous intraabdominal operation (i.e., virgin abdomen, VA) is unclear. The aim of this study was to clarify the clinical effect of WSCA for SBO in the VA. METHODS: Between January 2008 and December 2015, 838 consecutive patients with SBO were initially managed with WSCA and were included in the study. Abdominal X-rays were taken 5 h after administration of 100 ml WSCA and classified into complete/incomplete obstruction groups. The medical records of the patients with SBO were retrospectively analyzed and divided into two groups of patients with VA or non-VA. RESULTS: A total of 44 and 794 VA and non-VA patients were identified, respectively. Six VA patients (13%) and 121 non-VA patients (15%) were classified with complete obstruction (p = 1.000) and subjected to operative exploration on the same day. There were no significant differences in the duration of nasogastric tube decompression (2.2 versus 2.5 days, p = 0.400) and intervals until the initiation of oral intake (2.4 versus 2.6 days, p = 0.553) between the VA and non-VA groups. The overall operative rate was 16% in the VA and 17% in the non-VA groups (p = 1.000). Compared with non-VA, VA was associated with shorter hospital stays (9.6 versus 11.3 days, p = 0.006). CONCLUSIONS: WSCA for SBO in the VA is as effective as in non-VA patients in terms of a therapeutic strategy.

Differences in the impact of prognostic factors for hepatocellular carcinoma over time.

The aim of the present study was to evaluate the prognostic significance of serum markers that reflect tumor progression, liver function, or liver fibrosis in patients with hepatocellular carcinoma (HCC), focusing on how their impact changes over time after diagnosis. Alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin (DCP), albumin-bilirubin (ALBI) score, aspartate aminotransferase to platelet ratio index (APRI), and FIB-4 index were measured at the time of initial non-recurrent HCC diagnosis in 1669 patients between 1997 and 2016. Survival rates after diagnosis were compared after stratifying patients by these markers. Time-dependent receiver-operating characteristics (ROC) analysis was carried out to assess how these markers predict patient survival or death. Serum AFP and DCP levels, ALBI score, and APRI and FIB-4 index were strongly correlated with HCC progression, liver function, and degree of liver fibrosis, respectively. Survival rates after diagnosis were significantly different when patients were stratified by these markers. In the time-dependent ROC analysis, AFP and DCP had a high prognostic impact within 3 years of diagnosis but the impact decreased thereafter. In contrast, APRI and FIB-4 index had higher prognostic impact 10 years after diagnosis. ALBI score had a high prognostic impact throughout the study period. Time-dependent ROC analysis clearly showed changes in the prognostic importance of serum markers based on the duration after diagnosis. Whereas the prognostic impact of tumor progression markers was strong in the short term, liver fibrosis markers had higher prognostic impact long after diagnosis. Liver function had constant prognostic impact on patient survival after diagnosis.

Heat shock protein 22 (HSPB8) reduces the migration of hepatocellular carcinoma cells through the suppression of the phosphoinositide 3-kinase (PI3K)/AKT pathway.

Small heat shock proteins (HSPs) regulate a variety of cell functions. Among them, HSP22 and HSP20 are recognized to be ubiquitously expressed in various tissues. With regard to hepatocellular carcinoma (HCC) cells, we previously reported that phosphorylated HSP20 plays a suppressive role in transforming growth factor (TGF)-α-induced cell migration and invasion. In the present study, we investigated whether or not HSP22 is implicated in HCC cell migration. We detected HSP22 protein expression both in human HCC tumor (189.9±68.4ng/mg protein) and the adjacent non-tumor liver tissues (167.9±94.6ng/mg protein). The cases of low-quantity HSP22 protein level group (88.3≧ng/mg protein, the optimum cut-off value of HSP22) were increased in tumor tissues compared with the adjacent non-tumor tissues. The migration of human HCC-derived HuH-7 cells stimulated by TGF-α or hepatocyte growth factor (HGF) was significantly enhanced by the knockdown of HSP22 expression. Down-regulation of HSP22 protein in the cells markedly strengthened the AKT phosphorylation induced by TGF-α or HGF. Inhibitors of the phosphoinositide 3-kinase (PI3K)/AKT pathway, which suppressed the TGF-α-induced migration, significantly reduced the amplification by HSP22 knockdown. PI3K but not AKT was coimmunoprecipitated with HSP22 in HuH-7 cells. In addition, in human HCC tissues, a significantly lower HSP22 protein level in tumor tissues than in adjacent non-tumor tissues was observed more frequently in cases of moderately or poorly differentiated HCC than well-differentiated HCC. Taken together, our results strongly suggest that HSP22 represses HCC progression, especially HCC cell migration, by the down-regulation of the PI3K/AKT signaling pathway.

Phase II trial of neoadjuvant chemotherapy with S-1 and oxaliplatin plus bevacizumab for colorectal liver metastasis (N-SOG 05 trial).

PURPOSE: This Phase II trial evaluated the safety and efficacy of neoadjuvant chemotherapy (NAC) with S-1 and oxaliplatin (SOX) plus bevacizumab (Bev) in patients with colorectal liver metastasis (CRLM). METHODS: Patients with initially resectable CRLM received four cycles of SOX plus Bev as NAC. We adopted the R0 resection rate as the primary endpoint, and the threshold R0 resection rate was set at 80%. RESULTS: Between December 2010 and August 2014, 61 patients were enrolled in this study and all started NAC. The completion rate of NAC was 82.0%. Three patients (4.9%) developed severe liver dysfunction caused by NAC and one patient finally decided against resection. Three patients (4.9%) were judged as having progressive disease during or after NAC and did not undergo liver resection. Among 57 patients who underwent liver resection after NAC, three patients were diagnosed with CRLM by pre-treatment imaging modalities and received NAC although a final pathological diagnosis was another malignant disease or benign condition. Finally, 47 of the 54 patients (87.0%) with resected CRLM achieved R0 resection. The pathological complete response rate of the 54 patients was 13.0%, and 31.5% were judged as pathological responders. However, the R0 resection rate of 77.0% in the entire cohort did not meet the endpoint. CONCLUSIONS: NAC with SOX plus Bev has an acceptable toxicity profile and achieved a satisfactory pathological response. However, accuracy of pre-operative diagnoses and liver dysfunction caused by NAC were serious problems. Easy introduction of NAC for initially resectable CRLM should not be performed.