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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: 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.

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.

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.

While anti-p53 antibody (p53-Ab) is a potential marker for early detection of colorectal cancer, its clinical utility in patients with advanced colorectal cancer remains unknown. The clinical significance of p53-Ab was investigated by analyzing the data of 206 patients who underwent curative resection for colorectal liver metastases. Of the 206 patients, 60 (29%) were seropositive and 146 were seronegative for p53-Ab before the surgery. The preoperative serum p53-Ab level showed no significant correlation with the serum CEA or serum CA19-9 levels. The perioperative changes in serum p53-Ab positivity were significantly correlated with the preoperative serum p53-Ab levels and multivariate analysis confirmed that a higher preoperative p53-Ab level was independently associated with a worse recurrence-free survival (hazard ratio [HR], 1.07; 95% CI, 1.01–1.13; P = 0.033 per + 100 U/mL), even after adjustments for other oncological factors, including the preoperative serum CEA level. Higher preoperative p53-Ab levels were associated with a higher risk of recurrence after curative resection of colorectal liver metastases.

AIM The number of patients with fatty liver disease (FLD) is increasing globally. Ethanol consumption in FLD is known to be associated with an increased risk of hepatocellular carcinoma (HCC), but the effects of alcohol consumption on the occurrence of multiple HCCs remain unclear. We explored the relationship between the daily ethanol intake and the HCC number. METHODS This single-center retrospective study enrolled 114 patients without viral or immune hepatitis undergoing first-line HCC treatment who had been diagnosed with FLD by abdominal ultrasonography or a liver biopsy at the same time as or before HCC detection. We categorized patients into four groups according to the daily alcohol consumption (

OBJECTIVES Tumor necrosis is often found in pancreatic ductal adenocarcinoma (PDAC). Objective histological assessment and adequate radiological detection of necrosis could be used as biomarkers for therapeutic decision. However, standardized clinical utility of necrosis remains unknown. Here, we aimed to determine the prognostic potential of histological and radiological evaluations of necrosis. METHODS We investigated histological necrosis in 221 patients, who underwent surgery for PDAC, and classified its size as small (≤5 mm) or large (>5 mm). We also evaluated poorly enhanced areas on preoperative computed tomography to assess their ability for predicting histological necrosis and postoperative prognosis. RESULTS Tumor necrosis was found in 115 patients (52%) and was related to tumor area, lymph node metastasis, and lymphovascular invasion. Size of necrosis was significantly associated with tumor area, perimeter of necrosis, circularity of necrosis, number of ruptured cancer glands, and presence of collagen bundle (P < 0.05 for all). Both presence of necrosis and their size were strongly correlated to postoperative prognosis. Patients with poorly enhanced areas showed worse prognosis (P < 0.01). CONCLUSIONS Our findings underline the capacity of histological and radiological assessment of tumor necrosis for prognosis prediction in PDAC.

An increasing number of patients with pancreatic ductal adenocarcinoma (PDAC) have undergone resection after neoadjuvant therapy (NAT). We have reported Area of Residual Tumor (ART) as a useful pathological assessment method to predict patient outcomes after post NAT resection in various cancer types. The aim of this study was to assess the prognostic performance of ART in PDAC resected after NAT. Sixty-three patients with PDAC after post NAT resection were analyzed. The viable residual tumor area was outlined and the measurement of ART was performed using morphometric software. The results were compared with those of the College of American Pathologist (CAP) regression grading. Of 63 cases, 39 (62%) patients received chemoradiation therapy and 24 (38%) received chemotherapy only. The median value of ART was 163 mm2. Large ART with 220 mm2 as the cut-off was significantly associated with lymphatic invasion, vascular invasion and perineural invasion, while CAP regression grading was not associated with any clinicopathological features. By multivariate analysis, large ART (≥220 mm2) was an independent predictor of shorter relapse free survival. Together with our previous reports, an ART-based pathological assessment may become a useful method to predict patient outcomes after post NAT resection across various cancer types.

Pancreas-sparing duodenectomy (PSD) represents an alternative procedure to pancreatoduodenectomy (PD) for patients with duodenal neoplasms. The postoperative early and late complications of 21 patients who underwent PSD between 1992 and 2014 were compared with those of 44 patients with soft pancreatic parenchyma who underwent PD between 2009 and 2014. The median operation time and blood loss were less in the PSD group than in the PD group (P

Postoperative pancreatic fistula (POPF) is a serious complication of pancreaticoduodenectomy (PD). Sarcopenia is a newly identified marker of frailty. We performed this study to assess whether preoperative sarcopenia has an impact on clinically relevant POPF formation.A total of 266 consecutive patients who underwent a PD between 2010 and 2014 were enrolled in this retrospective study. Skeletal muscle mass was measured using preoperative computed tomography images. The impact of preoperative sarcopenia on clinically relevant POPF formation was analyzed using univariate and multivariate analyses.Of the 266 patients, 132 (49.6 %) were classified as having preoperative sarcopenia. The rate of clinically relevant POPF formation was significantly higher in the sarcopenia group (22.0 vs. 10.4 %; P = 0.011). A multivariate logistic regression analysis showed that sarcopenia (odds ratio, 2.869; P = 0.007) was an independent risk factor for the development of clinically relevant POPF, along with a soft pancreas and a parenchymal thickness at the pancreatic resection site of ≥8 mm.Preoperative sarcopenia was identified as a strong and independent risk factor for clinically relevant POPF formation after PD. Perioperative rehabilitation and nutrition therapy may contribute to the prevention of POPF formation and a safer PD.

[Purpose] Kinematic and kinetic characteristics of the limb during side-hopping and hip/knee interaction during this motion have not been clarified. The purposes of this study were to examine the biomechanical parameters of the knee during side hop and analyze its relationship with clinical measurements of hip function. [Subjects and Methods] Eleven male college rugby players were included. A three-dimensional motion analysis system was used to assess motion characteristics of the knee during side hop. In addition, hip range of motion and muscle strength were evaluated. Subsequently, the relationship between knee motion and the clinical parameters of the hip was analyzed. [Results] In the lateral touchdown phase, the knee was positioned in an abducted and externally rotated position, and increasing abduction moment was applied to the knee. An analysis of the interaction between knee motion and hip function showed that range of motion for hip internal rotation was significantly correlated with external rotation angle and external rotation/abduction moments of the knee during the lateral touchdown phase. [Conclusion] Range of motion for hip internal rotation should be taken into consideration for identifying the biomechanical characteristics in the side hop test results.

Hepatopancreatobiliary surgery has a high incidence of postoperative morbidity, including incisional surgical site infection. Although several studies showed that subcuticular sutures reduced incisional surgical site infection in other fields of surgery, their impact on hepatopancreatobiliary surgery remains unknown. The aim of this study was to assess whether subcuticular sutures could reduce incisional surgical site infection in patients undergoing hepatopancreatobiliary surgery.A total of 436 consecutive patients underwent laparotomy and surgical resection for hepatopancreatobiliary tumors in our department from May 2013 to December 2015. We excluded among them, 8 patients with a follow-up period30 days and 1 patient with unclear operative information. The incidence of incisional surgical site infection was compared between use of subcuticular sutures and of stapling, using propensity score analyses.In the baseline cohort (n = 427), abdominal skin closure was performed by subcuticular sutures in 245 patients (57.4%) and by stapling in 182 patients (42.6%). The incidence of incisional surgical site infection was 5/245 (2.0%) in the subcuticular suture group and 21/182 (11.5%) in the stapling group (P. 01). In the propensity score-matched cohort (n = 318), patient demographics were well balanced between the two groups, and the incidence of incisional surgical site infection was 3/159 (1.8%) in the subcuticular suture group and 16/159 (10.0%) in the stapling group (P.01). Propensity score analyses, as well as simple regression analyses, showed subcuticular sutures could consistently reduce incisional surgical site infection (with odd ratios of about 0.20).Use of subcuticular sutures is preferred to stapling for the prevention of incisional surgical site infection in hepatopancreatobiliary surgery.

Background The invasive front of tumor can provide prognostic information in many cancers. We investigated the prognostic morphological factors at the invasive front including tumor differentiation (Difinv ) and tumor budding (Bud) in biliary tract cancer (BTC). Methods The resected specimen from the 299 BTC patients were examined. Intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder cancer, and ampulla of Vater cancer were found in 16%, 48%, 17%, and 19%, respectively. Difinv grade (G) 3 and Bud foci ≥5 were found in 47% and 10%. Tumor with Difinv G3 showed the high frequencies of Bud, vascular invasion (Ve) and nodal metastasis (LN) compared to tumor with Difinv G1/2 (Bud: 21% vs 0%, Ve: 71% vs 50%, LN: 52% vs 36%). Multivariate analysis revealed that the independent predictors were Difinv G3 (HR: 1.71), Bud foci ≥5 (HR: 2.14), Ve (HR: 1.56) and LN (HR: 2.59) in overall survival and were positive resection margin (HR: 1.71), Difinv G3 (HR: 1.75), Ve (HR: 1.50), and LN (HR: 2.19) in relapse free survival. Conclusion Poor differentiation at the invasive front of tumor was associated with poor prognosis and early relapse in BTC patients.