Newly established borderline resectable 1 (BR1) category is one of the favorable candidates for selecting the use of multidisciplinary combination therapy in patients with advanced hepatocellular carcinoma treated with systemic therapy.

BACKGROUND: The aim of this study was to evaluate the newly established oncological criteria of resectability of hepatocellular carcinoma (HCC) for selecting suitable candidates for systemic and combination therapy. METHODS: The data of 156 consecutive HCC patients with intrahepatic target nodules who had initially received systemic therapy (lenvatinib and atezolizumab plus bevacizumab) were reviewed. The patients were classified into three groups according to the novel oncological criteria for resectability (R, resectable; BR1, borderline resectable 1; and BR2, borderline resectable 2). The prognostic ability and clinical utility for selecting this population to receive combined use of multiple systemic sequential and locoregional therapy was then evaluated. Combined use of systemic sequential therapy with more than two agents and locoregional treatment was defined as multidisciplinary combination therapy (MCT), while systemic sequential therapy only and repeated locoregional treatment was defined as a single treatment procedure (STP). RESULTS: Patients classified as R and BR1 had significantly better overall survival (OS) compared with BR2 (R vs. BR2, p = 0.012; BR1 vs. BR2, p = 0.004). However, there was no significant difference between R and BR1 (p = 1.000), in spite of significantly worse oncological status in the BR1 patients. Following a R0 resection and MCT, the BR1 patients had significantly better OS compared with those receiving STP or no additional treatment (median OS, not reached vs. 25.2 months and 20.1 vs. 11.3 months, respectively; p = 0.034). CONCLUSIONS: In patients with advanced HCC with intrahepatic target nodules the BR1 category is one of the favorable candidates for selecting those to be treated with MCT strategies.

Disease-Free Interval and Tumor Stage Complementarily Predict the Biological Behavior of Recurrent Hepatocellular Carcinoma.

BACKGROUND: Currently used treatment algorithms were originally established based on the clinical outcomes of the initial treatment for primary hepatocellular carcinoma (HCC), and no strong evidence exists yet to suggest if these algorithms could also be applicable to patients with recurrent HCC after surgery. As such, this study sought to explore an optimal risk stratification method for cases of recurrent HCC for better clinical management. METHODS: Among the 1616 patients who underwent curative resection for HCC, the clinical features and survival outcomes of 983 patients who developed recurrence were examined in detail. RESULTS: Multivariate analysis confirmed that both the disease-free interval (DFI) from the previous surgery and tumor stage at recurrence were significant prognostic factors. However, the prognostic impact of DFI seemed different according to the tumor stages at recurrence. While curative-intent treatment showed strong influence on survival [hazard ratio (HR), 0.61; P < 0.001] regardless of the DFI in patients with stage 0 or stage A disease at recurrence, early recurrence (< 6 months) was a poor prognostic marker in patients with stage B disease. The prognosis of patients with stage C disease was exclusively influenced by the tumor distribution or choice of treatment than by the DFI. CONCLUSIONS: The DFI complementarily predicts the oncological behavior of recurrent HCC, with its predictive value differing depending on the tumor stage at recurrence. These factors should be considered for selection of the optimal treatment in patients with recurrent HCC after curative-intent surgery.

The Impact of Lenvatinib on Tumor Blood Vessel Shrinkage of Hepatocellular Carcinoma during Treatment: An Imaging-Based Analysis.

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.

Risk Stratification of Patients with Marginal Hepatic Functional Reserve Using the Remnant Hepatocyte Uptake Index in Gadoxetic Acid-Enhanced Magnetic Resonance Imaging for Safe Liver Surgery.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: rHUI could be a sensitive substitute measure for posthepatectomy liver failure risk estimation among patients with marginal hepatic functional reserve.

A preoperative risk score based on multifrequency bioelectrical impedance analysis in patients undergoing liver resection.

PURPOSE: To investigate if body composition parameters measured by bioelectrical impedance analysis (BIA) and are reportedly correlated with clinical outcomes of patients undergoing digestive tract surgery could be useful for reliably evaluating the perioperative risk in patients undergoing hepatectomy. METHODS: Consecutive 200 patients who underwent BIA before hepatectomy were retrospectively reviewed. A risk prediction model for postoperative morbidity was created using the initial 100 patients, and its performance was validated using the remaining 100 patients. RESULTS: Based on the correlation with postoperative morbidity, a novel risk prediction model, the protein-edema score, was created using net protein weight and extracellular water/total body water ratio measured through BIA. The protein-edema score (score 0 vs. ≥ 1) showed a reproducible correlation with Clavien-Dindo 2 or greater postoperative morbidity in the validation set (17.7% vs. 46.4%, P = 0.002) as observed in the training set (18.8% vs. 49.0%, P = 0.002) after statistical adjustment. Similar tendency was also confirmed in Clavien-Dindo 3a or greater postoperative morbidity (5.9% vs. 18.2%, P = 0.037) and postoperative refractory ascites (5.5% vs. 17.4%, P = 0.037) in the validation set. CONCLUSIONS: The protein-edema score created based on BIA is significantly correlated with postoperative morbidity in patients undergoing liver resection.

Efficacy and safety of postoperative preemptive use of tolvaptan for patients with cirrhosis undergoing hepatectomy for hepatocellular carcinoma.

PURPOSE: Optimal choice of diuretics in perioperative management remains unclear in enhanced recovery after liver surgery. This study investigated the efficacy and safety of tolvaptan (oral vasopressin V2-receptor antagonist) in postoperative management of patients with liver injury and hepatocellular carcinoma. METHODS: The patients clinically diagnosed with liver cirrhosis were included in this study. Clinical outcomes of 51 prospective cohort managed with a modified postoperative protocol using tolvaptan (validation group) were compared with 83 patients treated with a conventional management protocol (control group). RESULTS: Postoperative urine output were significantly larger and excessive body weight increase were reduced with no impairment in renal function or serum sodium levels in the validation group. Although the total amount of discharge and trend of serum albumin level were not significantly different among the groups, global incidence of postoperative morbidity was less frequent (19.6% vs. 44.6%, P=0.005) and postoperative stay was significantly shorter (8 days vs.10 days, P=0.008) in the validation group compared with the control group. CONCLUSIONS: Tolvaptan could be safely used for the patients with injured liver in postoperative management after hepatectomy and potentially advantageous in the era of enhanced recovery after surgery with its strong diuretic effect and better fluid management.

Subserosal vascular density predicts oncological features of T2 gallbladder cancer.

PURPOSE: Tumor sidedness (hepatic side vs. peritoneal side) reportedly predicts microvascular invasion and survival outcomes of T2 gallbladder cancer, although the actual histopathological mechanism is not fully understood. METHODS: The clinical relevance of tumor sidedness was revisited in 84 patients with gallbladder cancer using histopathological analysis of the vascular density of the gallbladder wall. RESULTS: Hepatic-side tumor location was associated with overall survival (OS) (hazard ratio [HR], 13.62; 95% confidence interval [CI], 2.09-88.93) and recurrence-free survival (RFS) (HR, 8.70; 95% CI, 1.36-55.69) in T2 tumors. The Adjusted Kaplan-Meier curve indicated a clear survival difference between T2a (peritoneal side) and T2b (hepatic side) tumors (P = 0.006). A review of 56 pathological specimens with gallbladder cancer and 20 control specimens demonstrated that subserosal vascular density was significantly higher on the hepatic side of the gallbladder, regardless of the presence of cancer (P < 0.001). Multivariate analysis also confirmed that higher subserosal vascular density was significantly associated with poor OS (HR, 1.73; 95% CI, 1.10-2.73 per 10 microscopic fields) and poor RFS (HR, 1.62; 95% CI, 1.06-2.49) in T2  gallbladder cancer. CONCLUSION: Higher subserosal vascular density may account for the higher incidence of cancer spread and the poor prognosis of T2b gallbladder cancer.

Pretreatment Positron Emission Tomography with 18F-Fluorodeoxyglucose May Be a Useful New Predictor of Early Progressive Disease following Atezolizumab plus Bevacizumab in Patients with Unresectable Hepatocellular Carcinoma.

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 <2 (18% vs. 33%, respectively). Moreover, TLR values ≥2 were significantly associated with higher e-PD rates compared with TLR values <2 (64% vs. 11%, respectively) and worse e-PFS (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.

Clinical impact of the new "twin U-stitch method" of pancreaticogastrostomy in pancreaticoduodenectomy.

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.

Successful Anatomic Resection of Tumor-Bearing Portal Territory Delays Long-Term Stage Progression of Hepatocellular Carcinoma.

BACKGROUND: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Prognostic Impact of Surgical Intervention After Lenvatinib Treatment for Advanced Hepatocellular Carcinoma.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: In selected patients with advanced HCC, conversion surgery after lenvatinib treatment may offer significant survival benefit as long as R0 resection is achieved.

Adipose Tissue Distribution Predicts Prognosis of Cirrhotic Patients Undergoing Hepatectomy for Hepatocellular Carcinoma.

BACKGROUND: 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). METHODS: 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. RESULTS: 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 < 0.001) and early recurrence stage to advanced disease or death (15.4% vs. 2.8%, P = 0.004), were higher in the high-VSR group, suggesting that patients with a higher VSR are vulnerable to disease progression. CONCLUSION: A high VSR was found to be an independent predictor of disease progression and poor prognosis for HCC patients with underlying liver cirrhosis having resection for HCC.

Pretreatment Positron Emission Tomography with 18F-Fluorodeoxyglucose May Be a Useful New Predictor of Overall Prognosis Following Lenvatinib Treatment.

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 <2 (78 vs. 62%), resulting in a similar PFS (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.

Potential and Clinical Significance of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography for Evaluating Liver Cancer Response to Lenvatinib Treatment.

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.

Effects of alcohol consumption on multiple hepatocarcinogenesis in patients with fatty liver disease.

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 (<20 g: non-alcoholic fatty liver disease, n = 45; 20-39 g: low-intermediate ethanol intake with FLD, n = 13; 40-69 g: high-intermediate ethanol intake with FLD, n = 31; ≥70 g: alcoholic fatty liver disease, n = 25). The relationship between the daily ethanol consumption and the number of HCCs (single or multiple) was examined. RESULTS: The risk of multiple HCCs was significantly higher in the high-intermediate ethanol intake with FLD (HR 2.89, 95% CI 1.04-8.02, P = 0.042) and alcoholic fatty liver disease (HR 3.14, 95% CI 1.07-9.22, P = 0.037) groups than in the others. A multivariate analysis showed that a daily ethanol intake ≥40 g was associated with a significantly increased risk of multiple HCCs (HR 2.82, 95% CI 1.16-6.88, P = 0.023). CONCLUSIONS: Our findings suggest that a high daily ethanol intake might lead to multiple hepatocarcinogenesis in patients with FLD.

Usefulness of Serum Anti-p53 Antibody Measurement in Patients Undergoing Hepatectomy for Colorectal Liver Metastases.

BACKGROUND: 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. METHODS: The clinical significance of p53-Ab was investigated by analyzing the data of 206 patients who underwent curative resection for colorectal liver metastases. RESULTS: 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. CONCLUSION: Higher preoperative p53-Ab levels were associated with a higher risk of recurrence after curative resection of colorectal liver metastases.

Postoperative Nutritional Status is Predictive of the Survival Outcomes in Patients Undergoing Resection of Stage III Colorectal Cancer.

BACKGROUND: Preoperative nutritional status is reportedly associated with the clinical outcomes in patients with colorectal cancer (CRC), although it remains inconclusive whether the preoperative nutritional status that may improve after surgery is truly predictive of the survival outcomes of patients with CRC. METHODS: Clinical records of patients with stage III CRC (n = 821) in whom curative resection had been achieved were retrospectively reviewed and the prognostic impact of nutritional status, determined by the controlling nutritional status (CONUT) score, was analyzed. RESULTS: The CONUT undernutrition grade was significantly associated with the overall survival rate (OS) in the original population (P < 0.0001). By adopting a cut-off value of CONUT score of ≥ 2 and adjustment for clinical variables using the inverse probability treatment weighting methods, the group with a preoperative CONUT score of ≥ 2 showed a worse OS as compared to the groups with a preoperative CONUT score of < 2 (P = 0.037). However, sub-analysis based on the dynamic changes in the CONUT score revealed that sustained malnutrition in the postoperative period was more frequent among patients with preoperative CONUT score of ≥ 2, and that the OS and recurrence-free survival rate (RFS) were significantly correlated with the "postoperative" nutritional status, irrespective of the preoperative nutritional status. Patients who showed improvements of the nutritional status after surgery showed a significantly longer OS and RFS. CONCLUSIONS: Sustained undernutrition or worsening of the nutritional status after colectomy may be associated with a worse OS and RFS after curative resection in patients with stage III CRC.

Significance of preoperative nutritional status as a predictor for short-term and long-term outcomes of patients undergoing surgery for stage IV colorectal cancer.

PURPOSE: The clinical impact of the preoperative nutritional status has not fully been understood in an aggressive surgical approach for stage IV colorectal cancer (CRC). METHODS: 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. RESULTS: 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 < 0.001) and the length of hospital stay (P < 0.001). Multivariate analysis confirmed the CONUT undernutrition grade was significantly associated with the survival outcomes in patients with stage IV CRC (light: hazard ratio [HR], 1.12; 95% CI, 0.80-1.58; moderate: HR, 1.54; 95% CI, 1.02-2.33; severe: HR, 3.61; 95% CI, 1.52-8.62). CONCLUSIONS: Preoperative nutritional status is a useful predictive marker for both the short- and long-term outcomes of surgical interventions for stage IV CRC.

Safety of bioabsorbable membrane (Seprafilim®) in hepatectomy in the era of aggressive liver surgery.

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.

Hyaluronic acid/ carboxymethyl cellulose-based adhesion barrier reduces surgical difficulty and complication in repeat hepatectomy.

BACKGROUND: There has been no solid evidence regarding the actual efficacy of adhesion barriers in liver surgery. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.