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Background The relationship between the prognosis and magnitude of a decrease in tumor blood flow according to estimated tumor differentiation remains unclear. This study investigated the relationship between reductions in the rate of mean computed tomography (CT) attenuation values and the clinical prognosis. Methods We evaluated 63 consecutive patients who received lenvatinib treatment for unresectable hepatocellular carcinoma (HCC). The oncological aggressiveness of the tumors was estimated using classification by dynamic CT enhancement patterns. The utility of changes in mean CT attenuation values of intra-hepatic targets during treatment to estimate the prognosis was investigated by calculating the progression-free survival (PFS) and post-progression survival (PPS). A multivariate analysis was used to identify potential confounders for the survival after progression during lenvatinib therapy. Results The rate of decrease in the mean CT attenuation value gradually increased according to the degree of deterioration in estimated tumor differentiation, and the rate of a decrease in attenuation ≥40% showed a tendency to increase (p=0.064). This trend was reflected by a better objective response in oncological aggressiveness heterogeneous enhancement patterns (Type-3 and Type-4) than a homogeneous enhancement pattern (Type-2) (83% vs. 56% of modified Response Evaluation Criteria in Solid Tumors). This resulted in a similar PFS between the groups (p=0.773), whereas the PPS was significantly worse when the rate of decrease in the attenuation value was ≥40% (p=0.012). A multivariate analysis confirmed that a rate of decease in attenuation value ≥40% was a poor prognostic factor for the PPS (hazard ratio, 2.993; 95% confidence interval, 1.196-7.490; p=0.019). Conclusion A rate of decrease in attenuation ≥40% may reflect a good response of a highly malignant tumor to lenvatinib. Therefore, this value may have utility as a surrogate marker for estimating the oncological aggressiveness of tumors and their associated prognosis.

This study aimed to explore the efficacy of gadoxetic acid-enhanced (Gd-EOB) magnetic resonance imaging (MRI) in surgical risk estimation among patients with marginal hepatic function estimated by indocyanine green (ICG) clearance test.This analysis focused on 120 patients with marginal hepatic functional reserve (ICG clearance rate of future liver remnant [ICG-Krem] 0.10). Preoperative Gd-EOB MRI was retrospectively reviewed, and the remnant hepatocyte uptake index (rHUI) was calculated for quantitative measurement of liver function. The predictive power of rHUI for posthepatectomy liver failure was compared with several clinical measures used in current risk estimation before hepatectomy.Receiver operating curve analysis showed that rHUI had the best predictive power for posthepatectomy liver failure among the tested variables (ICG-R15, ICG-Krem, albumin + bilirubin score, and albumin + ICG-R15 score). Cross-validation showed that a threshold of 925 could be the best cut-off value for estimating the postoperative risk of liver failure with sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of 0.689, 0.884, 5.94, and 0.352, respectively.rHUI could be a sensitive substitute measure for posthepatectomy liver failure risk estimation among patients with marginal hepatic functional reserve.

PURPOSE The optimal pancreaticogastrostomy (PG) method for reducing pancreatic fistula (PF) incidence remains unclear. This retrospective review aimed to evaluate the clinical impact of the "twin U-stitch method" and compared it with the conventional invagination method. METHODS Data of 183 consecutive patients who underwent PG after pancreaticoduodenectomy (PD) between January 2015 and November 2020 were evaluated. PF incidence was compared between patients who experienced twin U-stitch PG (twin U-stitch group) and those who experienced conventional invagination PG (conventional PG group). RESULTS The twin U-stitch and conventional PG methods were performed in 97 and 86 patients, respectively. The time required for twin U-stitch PG was shorter than conventional PG (9.3 min vs 20.0 min, P < 0.001). The twin U-stitch group showed a lower incidence of PF than the conventional PG group (8% vs. 19%, P = 0.038). Multivariate analysis confirmed that twin U-stitch PG was significantly correlated with a decreased risk of PF (odds ratio, 0.23; P = 0.006), independent of the texture of the pancreas. Subgroup analysis of patients with soft-textured pancreas showed that the median drain amylase levels in the twin U-stitch group on postoperative days (POD) 1 and 3 were significantly lower than those in the conventional PG group (POD 1: 1,335 vs. 5,991 U/L, P < 0.001; POD 3: 212 vs. 518, P = 0.001). CONCLUSION The twin U-stitch method was simple and preferable to the conventional method for preventing PF in patients with PD.

The clinical impact of the preoperative nutritional status has not fully been understood in an aggressive surgical approach for stage IV colorectal cancer (CRC). The clinical records of 399 patients with stage IV CRC who underwent surgery for the primary tumor were reviewed. The predictive powers of reported nutritional/inflammatory indices of postoperative morbidity were compared, and their correlations with both the short- and long-term outcomes were investigated. Among the 10 tested nutritional/inflammatory indices, the Controlling Nutritional Status (CONUT) score showed the highest performance for predicting major morbidity (area under the curve [AUC], 0.605; P = 0.067) and any morbidity (AUC, 0.605; P = 0.001). When stratifying the population into 4 undernutrition grades based on the CONUT score, the CONUT undernutrition grades were found to show good correlations with the Clavien-Dindo grades of postoperative morbidity (P

There has been no solid evidence regarding the actual efficacy of adhesion barriers in liver surgery.Difficulty grade of lysis of adhesion was evaluated in 122 patients who underwent repeat hepatectomy (ReHx) using the TORAD score. Technical difficulty of lysis of adhesion and incidence of complication were then compared between the group of patients who received a sheet-type adhesion barrier (Seprafilm®) in the previous hepatectomy (n = 70) and those who did not (n = 52) using the inverse probability weighting method.Use of Seprafilm was significantly associated with lower grade of difficulty of lysis of adhesion according to the TORAD score (P 0.001). Postoperative morbidity rate was lower and postoperative stay was shorter in the Seprafilm group in the propensity-score adjusted population (37% vs. 74%, P 0.001 and 12 days vs. 14 days in median, P = 0.048). Multivariate analysis confirmed that use of Seprafilm was independent predictor for severity of adhesion (odds ratio [OR] 0.24, 95% CI, 0.09-0.65, P = 0.005) and decreased incidence of postoperative morbidity at ReHx (OR, 0.34; 95% CI, 0.14-0.84, P = 0.020).Use of Seprafilm may be associated with decreased technical difficulty of lysis of adhesion and may correlate with lower risk of postoperative morbidity in patients undergoing ReHx.

The aims of this study were to evaluate the clinical impact of curative-intent subsequent treatment on overall prognosis in lenvatinib-treated hepatocellular carcinoma (HCC) patients.Eighty-three consecutive patients with intrahepatic target nodules who received lenvatinib were reviewed. The clinical impact of curative-intent subsequent treatments was investigated through analysis of overall survival (OS) according to pathological deterioration stratified by mALBI grade.In patients with mALBI grade 1 and 2a liver function, R0 resection and lenvatinib-transarterial chemoembolization (lenvatinib-TACE) sequential therapy resulted in significantly better OS compared with other, non-curative-intent subsequent therapy and lack of additional treatment (median OS, 37.6 vs 29.0 months and 17.1 vs 8.9 months, respectively; P 0.001). Multivariate analysis confirmed that use of R0 resection and lenvatinib-TACE sequential therapy were associated with better OS (hazard ratio [HR], 0.021; P 0.001 and 0.108; P 0.001) compared with other, non-curative-intent subsequent treatment (HR 0.256; P = 0.010). In contrast, in patients with mALBI grade 2b liver function, multivariate analysis confirmed higher treatment efficacy for non-curative-intent subsequent treatment with respect to OS (HR 0.041; P 0.001) compared with R0 resection and lenvatinib-TACE sequential therapy (HR 0.057; P = 0.027 and 0.063; P = 0.001).Curative-intent subsequent treatment is more useful for HCC patients with better liver function (mALBI grade 1 and 2a) and intrahepatic target nodules who have received lenvatini b-based treatment.

Several therapeutic regimens, including neoadjuvant chemoradiation therapy (NACRT), have been reported to serve as anticancer immune effectors. However, there remain insufficient data regarding the immune response after NACRT in pancreatic ductal adenocarcinoma (PDAC) patients. Data from 40 PDAC patients that underwent surgical resection after NACRT (NACRT group) and 30 PDAC patients that underwent upfront surgery (US group) were analyzed to examine alterations in immune cell counts/distribution using a multiplexed fluorescent immunohistochemistry system. All immune cells were more abundant in the cancer stroma than in the cancer cell nest regardless of preoperative therapy. Although the stromal counts of CD4+ T cells, CD20+ B cells, and Foxp3+ T cells in the NACRT group were drastically decreased in comparison with those of the US group, counts of these cell types in the cancer cell nest were not significantly different between the two groups. In contrast, CD204+ macrophage counts in the cancer stroma were similar between the NACRT and US groups, while those in the cancer cell nests were significantly reduced in the NACRT group. Following multivariate analysis, only a high CD204+ macrophage count in the cancer cell nest remained an independent predictor of shorter relapse‐free survival (odds ratio = 2.37; P = .033). NACRT for PDAC decreased overall immune cell counts, but these changes were heterogeneous within the cancer cell nests and cancer stroma. The CD204+ macrophage count in the cancer cell nest is an independent predictor of early disease recurrence in PDAC patients after NACRT., This study sought to investigate any potential alterations in the distribution and clinical impact of immune cells in patients with pancreatic ductal adenocarcinoma (PDAC) treated with neoadjuvant chemoradiation therapy (NACRT). The present analysis revealed that NACRT for PDAC decreased overall immune cell counts, but these changes were heterogeneous within the cancer cell nests and cancer stroma. The CD204+ macrophage count in the cancer cell nest is an independent predictor of early disease recurrence in PDAC patients after NACRT.

With the introduction of new molecular-targeted agents, an increasing number of patients with advanced hepatocellular carcinoma (HCC) are benefiting from salvage interventions; however, the actual rate of conversion surgery and its prognostic advantages remain unclear. The clinical outcomes of 107 consecutive patients who underwent lenvatinib treatment for advanced HCC were reviewed and the efficacy of additional therapy, including surgery, was investigated. Of the 107 patients who were initially unsuitable for curative-intent therapy or transarterial chemoembolization (TACE), 54 (50.5%) received further therapy after lenvatinib treatment (surgery [n = 16] and TACE or other treatments [n = 38]). Of the 16 patients who received surgical intervention, R0 resection was achieved in 9 (8.4%) patients. Survival analysis confirmed that successful conversion to R0 resection was associated with a longer time to treatment failure (hazard ratio [HR] 0.04, 95% confidence interval [CI] 0.01–0.29; p = 0.002) and better disease-specific survival (HR 0.04, 95% CI 0.01–0.30; p = 0.002) compared with no additional treatment, while additional treatment other than surgery or R2 resection was associated with only a marginal or no prognostic advantage. Multivariate analysis confirmed that a decrease in plasma des-gamma-carboxyprothrombin levels compared with baseline levels (odds ratio 22.22, 95% CI 3.42–144.29; p = 0.001) was significantly correlated with successful R0 resection after lenvatinib treatment, irrespective of the tumor response as assessed by imaging analysis. In selected patients with advanced HCC, conversion surgery after lenvatinib treatment may offer significant survival benefit as long as R0 resection is achieved.

Background Repeat hepatectomy has been recognized as an effective treatment for hepatic malignancies, and a sheet type adhesion barrier, Seprafilm® has increasingly been used during hepatectomy to ease future relaparotomy. However, there is not yet sufficient evidence to support the safety of use of Seprafilm in liver surgery. Methods Data of 151 patients who had undergone open hepatectomy were retrospectively reviewed and the incidence of major abdominal morbidity was compared between patients in whom Seprafilm had and had not been used. Results Seprafilm was used in 108 patients (Seprafilm group) and no adhesion barrier was used in 43 patients (comparison group). There was no significant difference in the rate of major abdominal morbidities between the two groups (Seprafilm vs. comparison: 10% vs. 16%, P = 0.403). Although the Seprafilm group showed a tendency toward increased incidence of bile leakage (7% vs. 2%), and placement of Seprafilm on the hepatoduodenal ligament or on the visceral surface of the liver seemed to be associated with an increased incidence of major morbidity, multivariate analysis showed no significant correlation between the use of Seprafilm and postoperative major abdominal morbidity. Conclusion Use of Seprafilm may not increase the risk of major abdominal morbidity in liver surgery.

Body composition data are reportedly correlated with patient prognosis for various cancers. However, little is known about the prognostic impact of adipose tissue distribution among patients with hepatocellular carcinoma (HCC). Data for 181 consecutive cirrhotic patients who underwent hepatectomy for HCC were retrospectively reviewed. The clinical significance of the visceral-to-subcutaneous adipose tissue ratio (VSR) was investigated through analysis of short- and long-term surgical outcomes. Of the 181 patients, 60 (33%) were classified as the high-VSR group and 121 (67%) as the low-VSR group. Although VSR was not correlated with a risk of postoperative morbidity, multivariate analysis confirmed that a higher VSR was significantly correlated with a shorter time to interventional failure (hazard ratio [HR] 2.24; P = 0.008) and overall survival (HR 2.65; P = 0.001) independently of American Joint Committed on Cancer stage or preoperative nutritional status. Analysis of the recurrence patterns showed that the proportion of unresectable recurrence at the initial recurrence event was significantly higher in the high-VSR group (39% vs. 18%; P = 0.025). The yearly transition probabilities, defined by a Markov model from postoperative R0 status to advanced disease or death (7.6% vs. 1.5%, P

Background and Aim: The aim of this study was to identify the utility of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) as a predictor of overall prognosis in patients with hepatocellular carcinoma treated with lenvatinib. Methods: Forty-eight consecutive patients who received lenvatinib treatment were reviewed. The oncological aggressiveness of tumors estimated using 18F-FDG-PET/CT was investigated by the analysis of progression-free survival (PFS), post-progression survival (PPS), and overall survival (OS). Multivariate analysis was used to identify potential confounders for OS during lenvatinib therapy. Results: Using the Modified Response Evaluation Criteria in Solid Tumors, a tumor-to-normal liver ratio (TLR) ≥2, indicating higher oncological aggressiveness in HCCs, was associated with a better objective response to lenvatinib than a TLR p = 0.751). Because of a significantly worse PPS, OS with a TLR ≥2 was poor compared to a TLR < 2 (p = 0.012). Multivariate analysis confirmed that a TLR ≥ 2 was associated with poor OS (hazard ratio, 2.709; 95% CI, 1.140–6.436; p = 0.024). Analysis of 24 patients who received a repeat 18F-FDG-PET/CT showed that daily changes expressed as ΔTLR × 103/day over the treatment course tended to be different among the types of subsequent treatment. A R0 resection and lenvatinib-TACE sequential therapy provided good disease control (median, −4.593 and −0.024, respectively) compared with other treatments (median, 5.278) (p = 0.075). Conclusion: Lenvatinib has acceptable disease control regardless of estimated tumor differentiation. A high TLR (≥2) is a poor prognostic factor of OS following lenvatinib treatment, while ΔTLR × 103/day provides useful information of disease control status.

Introduction: When lenvatinib is administered to people with hepatocellular carcinoma (HCC), tumor blood flow is reduced due to the inhibition of the vascular endothelial growth factor receptor (VEGFR) and fibroblast growth factor receptor (FGFR). Few studies have examined the decrease in tumor blood flow with respect to changes in tumor blood vessels (TBVs) in clinical practice. We investigated the mechanism of tumor blood flow control by investigating changes in the diameter of relatively large TBVs in large-sized lesions with high blood flow. Methods: From January 2011 to October 2021, patients receiving lenvatinib for unresectable intrahepatic HCC at Toranomon Hospital, Tokyo, Japan, were considered for inclusion. We investigated the TBV diameter in the arterial phase of dynamic computed tomography before treatment and its change over time (2–12 weeks after lenvatinib initiation). The relationship between changes in TBV diameter and prognosis was also examined. Results: Of 114 patients treated with lenvatinib for HCC, 26 patients who had intrahepatic lesions with a tumor diameter of 30 mm or more enrolled in the study. The median tumor and TBV diameters before treatment were 58 mm and 2.55 mm, respectively. Twenty-five patients (96%) had a shrinkage in TBV diameter 2–12 weeks after lenvatinib administration. The maximum TBV diameter shrinkage of 20% or more was observed in 19 patients (73%), and progression-free survival was prolonged in these patients compared to the group with less than 20% TBV diameter shrinkage (p = 0.039). Discussion/Conclusion: Due to the antiangiogenic effect of lenvatinib, a shrinkage in the TBV diameter of HCC was observed. The shrinkage of TBV may be regarded as a process of normalization of TBVs. The shrinkage of TBVs in imaging analysis may be associated with improved prognosis; however, additional studies are still required.

Background and Aims: The aim of this study was to identify the utility of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) as a predictor of early progressive disease (e-PD) in patients with hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab (Atezo/Bev). Methods: Twenty consecutive patients with measurable intrahepatic target nodules who received Atezo/Bev treatment were reviewed. The oncological aggressiveness of tumors estimated by 18F-FDG-PET/CT was analyzed using the rate of e-PD within 12 weeks and early progression-free survival (e-PFS) and overall survival (OS). Multivariate analysis was used to identify potential confounders for PD during Atezo/Bev therapy. Results: Using the Response Evaluation Criteria in Solid Tumors version 1.1, a tumor-to-normal liver ratio (TLR) ≥2, indicating higher oncological aggressiveness in HCCs, was associated with lower objective response rates compared with TLR values p = 0.021). In multivariate analysis, TLR ≥2 showed marginal significance as a predictor of e-PD (p = 0.053), and utility as a predictor for worse e-PFS (hazard ratio, 7.153; 95% confidence interval, 1.258–40.689; p = 0.027). In contrast, no significant differences in OS with/without e-PD were observed during the treatment course. In this study, 8 patients experienced e-PD and almost 40% of patients experienced acceptable disease control following subsequent lenvatinib treatment. Conclusion: Pretreatment 18F-FDG-PET/CT may be a useful new predictor of e-PD and may enable early decision-making based on early treatment changes following Atezo/Bev treatment of HCC.

Background: The sensitivity of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in hepatocellular carcinoma (HCC) is low; however, clinical evidence demonstrating its prognostic value in patients with HCC has recently been reported. This study aimed to assess the value of 18F-FDG-PET/CT as a tool for evaluating the response of HCC to lenvatinib treatment. Methods: We evaluated 11 consecutive patients with HCC diagnosed by dynamic CT or magnetic resonance imaging combined with 18F-FDG-PET/CT from April 2018 to December 2019. The tumor-to-normal liver ratio (TLR) of the target tumor was measured before and during the course of lenvatinib treatment with 18F-FDG-PET/CT (pre and post analysis, respectively), with a TLR ≥2 classified as PET-positive HCC. At the time of each evaluation, we also used the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, the modified RECIST (mRECIST), and the tumor marker alfa-fetoprotein (AFP). Results: Of 11 patients, 3 (27%) and 8 (73%) had an objective response to lenvatinib treatment at the time of post-analysis by RECIST 1.1 and mRECIST, respectively. There were 3 (27%) and 7 (64%) patients with PET-positive HCC at the time of pre- and post-analysis, respectively. There was a significant correlation between the rates of change in AFP and TLR during lenvatinib treatment (r = 0.69, p = 0.019). Based on these results, we were able to perform liver resection on 4 patients with PET-positive HCC as conversion therapy. Three samples from these patients showed poorly differentiated tumors. Conclusion: 18F-FDG-PET/CT has potential as an evaluation tool for describing biological tumor behavior and reflecting disease progression, location, and treatment response. This modality may provide useful information for considering prognosis and subsequent therapy.

Background: The aims of this study were to evaluate the efficacy of additional treatment, especially lenvatinib-transarterial chemoembolization (TACE) sequential therapy, for unresectable hepatocellular carcinoma (HCC). Methods: Consecutive 56 patients who underwent lenvatinib treatment were reviewed. Oncological aggressiveness of tumor was estimated using a dynamic CT enhancement pattern classification, and clinical impact of subsequent treatment was investigated through analysis of progression-free survival (PFS), post-progression survival (PPS), and multivariate analysis of potential confounders for survival after progression during lenvatinib therapy. Results: Heterogeneous enhancement patterns (Type-3 and -4), which are reportedly associated with higher oncological aggressiveness of HCC, were associated with better objective response to lenvatinib compared to homogeneous enhancement pattern (Type-2) (86 and 85% vs. 53% in modified Response Evaluation Criteria in Solid Tumors), resulting in similar PFS (p = 0.313). Because of significantly worse PPS, overall survival of Type-4 tumor was poor compared to Type-2 or -3 tumors (p = 0.009). However, subgroup of patients who achieved subsequent treatment showed significantly better PPS, regardless of CT enhancement pattern. Multivariate analysis confirmed that use of lenvatinib-TACE sequential treatment after progression during lenvatinib therapy was associated with better PPS (hazard ratio [HR], 0.08; 95% CI, 0.01–0.71; p = 0.023), while Type-4 enhancement pattern was correlated with worse PPS (HR, 2.92; 95% CI, 1.06–8.05; p = 0.039). Conclusion: Oncological aggressiveness of HCC estimated by CT enhancement pattern was predictive of PPS after progression during lenvatinib. Successful subsequent treatment with lenvatinib-TACE sequential therapy may offer survival benefit regardless of CT enhancement pattern of HCC.

Highlights • We performed extended DP-CAR with resection of the confluence of GDA and PHA. • The presence of r-RHA could reduce the risk of ischemic complications. • Further, r-RHA could be a practical choice to expand surgical margin in DP-CAR., Background While distal pancreatectomy with celiac axis resection (DP-CAR) contributes to R0 resection for pancreatic body cancer, arterial blood flow to the liver from gastroduodenal artery is essential. However, in the presence of replaced right hepatic artery (r-RHA), extended DP-CAR (Ex-DP-CAR) in which the right edge of pancreatic resection includes the confluence of gastroduodenal artery (GDA) and proper hepatic artery (PHA) may be feasible. Herein, we report a patient with r-RHA and perform Ex-DP-CAR without reconstruction of PHA. Case presentation A 39-year-old man with pancreatic cancer, cT4N0M0 (UICC 8th), underwent DP-CAR after neoadjuvant chemotherapy (NAC). After laparotomy, unlike the evaluation in preoperative imaging, the tumor was found to invade the confluence of GDA and PHA. After confirmation of arterial blood flow to the liver, GDA and PHA was ligated and Ex-DP-CAR was completed with R0 margin status. The postoperative course was uneventful, with no recurrence 18 months after the surgery. Conclusion We performed Ex-DP-CAR with resection of the confluence of GDA and PHA in the presence of r-RHA, which has a potential role in expanding the surgical indications for R0 resection by reducing the risk of ischemic complications without reconstruction of arterial blood supply to the liver.

Adhesion barriers are increasingly used in hepatobiliary surgery. However, there has been no solid evidence yet in support of their safety. Incidences of global postoperative morbidities and major abdominal morbidities were compared between 101 consecutive patients who received a sheet-type adhesion barrier (Interceed®) and 134 patients who did not receive any adhesion barriers during hepatectomy. Propensity score (PS) adjustment was used to account for potential bias to receive Interceed. In the PS-adjusted population, the incidences of both global postoperative morbidities and major abdominal morbidities showed no significant difference between the Interceed group and the control group (17.9% vs. 17.6%; P = 0.948 and 7.8% vs. 9.1%; P = 0.813, respectively). Multivariate analysis showed that age + 10 years (odds ratio [OR], 1.70; 95% CI, 1.15–2.50; P = 0.007), estimated blood loss + 100 mL (OR, 1.05; 95% CI, 1.01–1.09, P = 0.009), and laparoscopic approach (OR, 0.10; 95% CI, 0.01–0.75; P = 0.026) were independent predictors for global postoperative morbidities and operation time + 1 h (OR, 1.56; 95% CI, 1.23–1.96; P

Optimal choice of surgical procedure for hepatocellular carcinoma (HCC) remains inconclusive. This study seeks to investigate the oncological superiority of anatomic resection (AR) of the tumor-bearing portal territory and potential mechanism of survival benefit for patients undergoing AR. In 203 patients who underwent curative resection for primary solitary HCC measuring ≤ 5 cm in diameter, which was resectable either by AR or limited resection (non-AR), long-term outcomes were compared with propensity score adjustment. Advantages of AR in local tumor control and postprogression survival were then evaluated by a multivariate analysis and a Markov model. The AR group showed better recurrence-free survival [hazard ratio (HR), 0.51; 95% CI, 0.28–0.91; P = 0.023), time-to-interventional failure (TIF) (HR, 0.08; 95% CI, 0.01–0.60; P = 0.014), and overall survival (HR, 0.11; 95% CI, 0.01–0.79, P = 0.029) than the non-AR group. Competing-risks regression revealed that AR significantly decreases local recurrence (HR, 0.13; 95% CI, 0.02–0.97; P = 0.047) and is correlated with smaller number and size of recurrent lesions, both of which were predictors for better TIF and postprogression survival. A Markov model demonstrated that annual transition rate from the early recurrence stage (i.e., curative-intent treatment indicated) to the intermediate stage (i.e., only palliative-intent treatment indicated) was significantly lower (9.0% versus 35.6%, P = 0.027) when AR was completed at the initial hepatectomy. AR is oncologically advantageous for patients with primary solitary HCC. Initial choice of surgical procedure may have significant influence on the pattern of recurrence and postprogression clinical course that may affect overall survival of patients with HCC.

Background Although adhesion barriers are increasingly used in liver surgery, there are no sufficient data yet in support of their safety. Methods Data of 104 consecutive patients in whom a spray-type adhesion barrier (AdSpray® ) was used after hepatectomy were compared with those of 94 control subjects in whom no adhesion barriers were used, and the risk factors for major morbidity after hepatectomy were investigated. Results The incidence of major morbidity was not significantly different between the AdSpray group and the control group (17% vs 15%, P = .645), although multivariate analyses revealed that the use of AdSpray was associated with an increased risk of abdominal abscess (odds ratio [OR], 4.42; P = .043). Similar tendency was also confirmed after propensity score adjustment to account for the potential selection bias. A sub-group analysis revealed that incidence of abscess formation decreased as operators' experience in the used of AdSpray increased, and multivariate analysis identified preoperative chemotherapy (OR, 3.96; P = .043) as being independent predictors of abscess formation after the use of AdSpray. Conclusions AdSpray use was not associated with global incidence of major morbidity after liver surgery, although surgeon's experience would be needed for adequate use of AdSpray to minimize the risk of postoperative abscess formation.

Background Repeat hepatectomy (ReHx) for recurrent hepatic malignancies reportedly provides oncological benefit for patients. However, severe adhesions at the time of ReHx may preclude safe and curative resection and there has been no reliable measure to estimate the surgical risk at ReHx. This study sought to create a new scoring system for evaluating the severity of adhesion after hepatectomy and tested its performance looking at the correlation with morbidity rate. Methods Operative videos of 66 patients undergoing a second hepatectomy were reviewed and the difficulty levels in lysis of adhesion around the hepatic hilum (A score) and surrounding the liver (B score) were scored by two examiners and validated by two additional reviewers. Results Very high interobserver agreement was confirmed between the two examiners (κ value, 0.960-0.963) and reproducibility of results were validated with weighted kappa values of >0.8 in both surgical resident and hepatobiliary surgeon. Linear correlation was confirmed between the difficulty score and postoperative morbidity rate. Multivariate analyses confirmed that previous cholecystectomy or transection of visceral surface of segment 4 or 5 was an independent factor predicting hard to extreme adhesions at the hepatic hilum regardless of the use of anti-adhesion materials. Conclusions The new difficulty scoring system for the lysis of adhesion at ReHx showed good interobserver agreement and reproducibility of the results. Given the strong correlation with postoperative morbidity rate, the present score could be used for evaluating the technical difficulties in ReHx and may offer a reliable measure for estimating the efficacy of anti-adhesion materials in future analysis.

Casimiroa edulis La Llave is known to contain unusual 5,6-dimethoxyflavones bearing a variously oxygenated B-ring. Phytochemical investigation of the leaves and the roots of C. edulis achieved the isolation of two new methoxylated flavones, named casedulones A (1) and B (2), together with 12 known analogues. Their unique structures were established with the aid of spectral analyses and total syntheses. Pre-treatment with 20 µM of 1 and 2 suppressed MMP-9 expression in LPS-mediated THP-1 cells, indicating that the characteristic flavonoids in C. edulis could be potential anti-angiogenics for cancer prevention.

Indocyanine green (ICG) fluorescence angiography is being increasingly performed intraoperatively to detect restricted blood flow intraoperatively for the prevention of postoperative organ ischemia and anastomotic leakage. This is the first case report of simultaneous laparoscopic distal gastrectomy (LDG) and spleen-preserving distal pancreatectomy (LSPDP) involving ICG angiography use to avoid the remnant stomach ischemia.A 55-year-old man was diagnosed with early cancer of the stomach body and intraductal papillary mucinous neoplasms of the pancreatic tail. We performed simultaneous LDG with D2 dissection and LSPDP to conserve the gastrosplenic ligament and preserve blood supply to the remnant stomach. Intraoperatively, blood flow to the remnant stomach was visualized using ICG fluorescence angiography, after which Roux-en-Y reconstruction was performed. There was no perioperative remnant stomach ischemia.Despite the preserved splenic artery and vein, complete splenic infarction occurs after LSPDP possibly due to thrombus formation during surgical procedures. In this patient, we conserved the gastrosplenic ligament for the short gastric artery, which supplied blood to the remnant stomach; however, remnant stomach ischemia may occur. Therefore, we performed ICG fluorescence angiography during this operation to ensure that sufficient blood supply to the remnant stomach was maintained.Our experience demonstrates that ICG angiography may be useful for the prevention of remnant stomach ischemia.

Background: Given the scarce evidence regarding the impact of preoperative nutritional status on surgical outcomes of patients with hepatocellular carcinoma, predictive powers of nutritional/inflammatory scores for short-term surgical outcomes in patients with hepatocellular carcinoma were investigated. Methods: Outcomes of 1272 patients with hepatocellular carcinoma were reviewed, and predictive powers of nine nutritional/inflammatory scores for short-term surgical outcomes were compared using the receiver-operating characteristic curve analysis. Clinical relevance of the best nutritional score was then studied in detail to clarify its utility as an alternative predictive measure for surgical risk of patients with hepatocellular carcinoma. Results: Receiver-operating characteristic curve analysis showed the controlling nutritional status score has the best performance in prediction of morbidity after hepatectomy for hepatocellular carcinoma (area under the curve, 0.593; 95% confidence interval: 0.552–0.635; p Conclusions: The controlling nutritional status score could be an alternative measure for underlying liver injury and the surgical risk of hepatocellular carcinoma.

As diamond possesses only deep dopants, certain conventional physics and characterization methods are not applicable to diamond devices, owing to the explicit or implicit assumption of shallow dopants. To resolve this limitation, the capacitance –voltage ( C–V) characteristics of metal–insulator–semiconductor (MIS) capacitors formed on a semiconductor substrate with deep and compensating dopants were successfully formulated. Based on these equations, methods for accurately estimating the MIS capacitor properties were developed and validated through their application in the analysis of an actual MIS capacitor formed on a boron-doped hydrogen-terminated diamond substrate. The high-frequency C–V characteristic of the capacitor exhibited a prominent dip specific to deep dopants. However, the dip depth was considerably shallower than theoretically expected. This C–V characteristic was accurately reproduced theoretically, assuming the presence of a surficial diamond layer that contains acceptors with an activation energy of 0.23 eV, which is less than the value 0.37 eV for boron, and has a thickness of the extrinsic Debye length (40 nm in this study) or larger. The insulator charge of the MIS capacitor was estimated as −4.6 × 1012 cm−2 in units of electronic charge, which is sufficiently large to induce two-dimensional hole gas. The interface-state density was 1.4 × 1012 cm−2 eV−1 for interface-state energies of 0.3–0.5 eV above the valence band maximum. Hence, the proposed methodology and the possible presence of the reduced activation energy layer will guide the development of diamond-based devices.

BACKGROUND The actual efficacy of use of adhesion barriers during liver surgery remains to be fully understood. METHODS We conducted an extensive review of clinical data and operation videos of 210 patients who underwent repeat hepatectomy to clarify the factors associated with the degree of adhesion as evaluated by the TORAD score. RESULTS Adhesion barriers were placed in 131 patients (Seprafilm® [n = 77], Adspray® [n = 32], and Interceed® [n = 22)]), but not in the remaining 79 patients during the previous surgery. Multivariate analysis identified a high adhesion severity score at relaparotomy as being associated with an increased risk of postoperative global morbidity (odds ratio [OR], 1.75 per +1 point, P

Humoral factors from cancer-associated fibroblasts (CAFs) reportedly affect epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance in cancer cells with EGFR mutations. The aim of this study was to identify the robust humoral factors secreted from CAFs that induce the primary resistance to EGFR-TKI. We evaluated the EGFR-TKI sensitivity of EGFR-mutant lung adenocarcinoma cell line (PC-9) treated with condition media (CM) from 18 cases of CAFs and matched non-cancerous-tissue-associated fibroblasts (NCAFs). We measured the expression levels of hepatocyte growth factor (HGF), interleukin-6, fibroblast growth factor-2, insulin-like growth factor-1, and vascular endothelial growth factor-A in CAFs and NCAFs. We examined whether HGF neutralizing antibody could annul the EGFR-TKI resistance induced by CM from CAFs. Compared to CM from NCAFs, CM from CAFs increased the resistance of PC-9 cells to EGFR-TKI in five out of 18 cases. Relative expression ratio of HGF messenger RNA was significantly higher in these five CAFs compared to others (P = 0.0013), whereas other cytokines were not. In four of these five cases, the addition of HGF neutralizing antibody significantly decreased the survival ratio of PC-9 cells. This study suggests that the secretion of higher amounts of HGF is the robust feature of EGFR-TKI resistance-promoting CAFs.

Diamond is a promising material for power applications owing to its excellent physical properties. Two-dimensional hole gas (2DHG) diamond metal–oxide–semiconductor field-effect transistors (MOSFETs) with hydrogen-terminated (C-H) channel have high current densities and high breakdown fields but often show normally- ON operation. From the viewpoint of safety, normally- OFF operation is required for power applications. In this letter, we used ion implantation to form a shallow and thin nitrogen-doped layer below the C-H channel region, which realized normally- OFF operation. Nitrogen-ion implanted length is fixed at 5 or 10 $\mu \text{m}$ . Nitrogen is a deep donor (1.7 eV) and the nitrogen-doped layer prevents hole accumulation near the surface. The threshold voltage was as high as −2.5 V and no obvious dependence on the threshold voltage of nitrogen-ion implanted length is observed. The breakdown field was 2.7 MV/cm at room temperature. Of 64 devices with a common gate length, 75% showed normally- OFF operation. We confirmed the threshold voltage shift by a thin and shallow nitrogen-doped layer formed by ion implantation.

This letter reports the small-signal and large-signal performances at high drain voltage ( $\text{V}_{\textsf {DS}}$ ) ranging up to 60 V for a 0.5 $\mu \text{m}$ gate length two-dimensional hole gas diamond metal-oxide-semiconductor field-effect transistor with a 100-nm-thick atomic-layer-deposited Al2O3 film on a IIa-type polycrystalline diamond substrate with (110) preferential surfaces. This diamond FET demonstrated a cutoff frequency ( $\text{f}_{\textsf {T}}$ ) of 31 GHz, indicating that its carrier velocity was reaching $\textsf {1.0}\times \textsf {10}^{\textsf {7}}$ cm/s for the first time in diamond. In addition, a $\text{f}_{\textsf {T}}$ of 24 GHz was obtained at $\text{V}_{\textsf {DS}}=-\textsf {60}$ V, thus giving a $\text{f}_{\textsf {T}}\times \textsf {V}_{\textsf {DS}}$ product of 1.44 THz $\cdot \text{V}$ . This diamond FET is promising for use as a high-frequency transistor under high voltage conditions. Under application of a high voltage, a maximum output power density of 3.8 W/mm (the highest in diamond) with an associated gain and power added efficiency were 11.6 dB and 23.1% was obtained when biased at $\text{V}_{\textsf {DS}}=-\textsf {50}$ V using a load-pull system at 1 GHz.