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Background: Although the prognostic relevance of KRAS status in metastatic colorectal cancer (CRC) depends on tumor laterality, this relationship is largely unknown in non-metastatic CRC. Methods: Patients who underwent resection for non-metastatic CRC between 2000 and 2018 were identified from institutional databases at six academic tertiary centers in Europe and Japan. The prognostic relevance of KRAS status in patients with right-sided (RS), left-sided (LS), and rectal cancers was assessed. Results: Of the 1093 eligible patients, 378 had right-sided tumors and 715 had left-sided tumors. Among patients with RS tumors, the 5-year overall (OS) and recurrence-free survival (RFS) for patients with KRASmut versus wild-type tumors was not shown to differ significantly (82.2% vs. 83.2% and 72.1% vs. 76.7%, respectively, all p >.05). Among those with LS tumors, KRAS mutation was associated with shorter 5-year OS and RFS on both the univariable (OS: 79.4% vs. 86.1%, p =.004; RFS: 68.8% vs. 77.3%, p =.005) and multivariable analysis (OS: HR: 1.52, p =.019; RFS: HR: 1.32, p =.05). Conclusions: KRAS mutation status was independently prognostic among patients with LS tumors, but this association failed to reach statistical significance in RS and rectal tumors. These findings confirm reports in metastatic CRC and underline the possible biologic importance of tumor location.

The aim of this study was to determine the incidence of high-grade dysplasia (HGD) or invasive carcinoma in patients with small branch duct intraductal papillary mucinous neoplasms (BD-IPMNs).923 patients who underwent surgical resection for an IPMN were identified. Sendai-negative patients were identified as those without history of pancreatitis or jaundice, main pancreatic duct size (MPD)5 mm, cyst size3 cm, no mural nodules, negative cyst fluid cytology for adenocarcinoma, or serum carbohydrate antigen 19-9 (CA 19-9)37 U/L.BD-IPMN was identified in 388 (46.4%) patients and 89 (22.9%) were categorized as Sendai-negative. Overall, 68 (17.5%) of BD-IPMN had HGD and 62 (16.0%) had an associated invasive-carcinoma. Among the 89 Sendai-negative patients, 12 (13.5%) had IPMNs with HGD and only one patient (1.1%) had invasive-carcinoma. Of note, older age (OR 1.13, 95% CI 1.03-1.23; P = 0.008) and minimal dilation of MPD (OR 11.3, 95% CI 2.40-53.65; P = 0.002) were associated with high-risk disease in Sendai-negative patients after multivariable risk adjustment.The risk of harboring a high-risk disease remains low in small BD-IPMNs. However, Sendai-negative patients who are older than 65 years old and those with minimal dilation of MPD (3-5 mm) are at greater risk of high-risk lesions and should be given consideration to be included as a "worrisome feature" in a future guidelines update.

OBJECTIVE To define frequencies, pattern of progression (invasive versus non-invasive), and risk factors of progression of resected non-invasive IPMNs BACKGROUND:: There is a risk of progression in the remnant pancreas after resection of intraductal papillary mucinous neoplasms (IPMNs). METHODS 449 consecutive patients with resected IPMNs from 1995-2018 were included to the study. Patients with invasive carcinoma or with follow-up < 6 months were excluded. Non-invasive progression was defined as a new IPMN, increased main pancreatic duct (MPD) size, and increased size of an existing lesion (5 mm compared to preoperative imaging). Invasive progression was defined as development of invasive cancer in the remnant pancreas or metastatic disease. RESULTS With a median follow-up of 48.9 months, progression was identified in 124 patients (27.6%); 108(24.1%) with non-invasive and 16(3.6%) with invasive progression. Median progression follow-up was longer for invasive progression (85.4 vs. 55.9 months; P = 0.001). Five- and 10-year estimates for a cumulative incidence of invasive progression were 6.4% and 12.9% versus 26.9% and 41.5% for non-invasive progression. After risk-adjustment, multifocality (HR 4.53, 95%CI 1.34-15.26; P = 0.02) and high-grade dysplasia (HGD) in the original resection (HR 3.60, 95%CI 1.13-11.48; P = 0.03) were associated with invasive progression. CONCLUSIONS Progression to invasive carcinoma can occur years after the surgical resection of a non-invasive IPMN. HGD in the original resection is a risk factor for invasive progression but some cases of low-grade dysplasia also progressed to cancer. Patients with high-risk features such as HGD and multifocal cysts should be considered for more intensive surveillance and represent an important cohort for future trials such as anti-inflammatory or prophylactic immunotherapy.

Background/aim Several studies have found elevated soluble CD40 Ligand (sCD40L) in the serum of patients with malignancies as well as those with inflammatory bowel disease (IBD). Our goal was to determine the possible causal role of sCD40L in colitis-associated colorectal cancer (CAC) by using the well-established azoxymethane/dextran sulfate sodium (AOM/DSS) protocol. Materials and methods Twelve wild type (WT) and twelve TLR4 knock out (KO) female C57BL6 mice were divided into 4 experimental groups. Six WT and six TLR4 KO mice were treated with a single intraperitoneal dose (10 mg/kg of body weight) of AOM followed by three 7-day cycles of oral 2.5% DSS. The other two groups included 6 WT and 6 TLR4 KO mice that received only water and served as the control groups. The mice were sacrificed after 84 days. Results All mice in the AOM/DSS WT group developed CAC while all mice from the AOM/DSS TLR4 KO group were protected from CAC. We measured the serum and pathologic tissue levels of sCD40L with quantitative sandwich enzyme-linked immunoassay (ELISA) and found that serum sCD40L was significantly higher in wild-type mice that developed CAC compared to their healthy counterparts (wild-type and TLR-4 KO controls). In comparison, serum sCD40L levels were comparable between TLR-4 KO mice, which are protected from developing CAC, and their healthy counterparts (wild-type and TLR-4 KO controls). Of note, tissue levels of sCD40L were not affected by the development of CAC. Conclusion Our findings point to the presence of an axis between TLR-4 and sCD40L, which may lead to decreased immunosurveillance and the subsequent development of colitis-associated cancer.

A preoperative goals-of-care discussion is essential in maintaining the autonomy of older adults who require surgery. The purpose of this study was to determine the accuracy of the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) risk calculator and its association with age for patients who underwent pancreatectomy.Using the American College of Surgeons NSQIP database, patients who underwent pancreatectomy between 2012 and 2015 were identified. Age was categorized into three groups: 18-64, 65-79, and 80-89 y. Analysis of variance and Pearson correlation coefficients were employed to assess differences between age categories in predicted and actual mortality and morbidity. Covariate-adjusted logistic regression models were employed to evaluate associations while accounting for potential confounders.A total of 17,906 patients were included. The correlation between actual and predicted mortality was low (r = 0.14, P 0.001). This correlation was weakest for the age category 80-89 y (r = 0.04, P = 0.07) and strongest for 65-79 y category (r = 0.14, P 0.001). The correlation was weakest among patients who underwent pancreatoduodenectomy (r = 0.06, P = 0.08) and in this group mortality was overestimated for older adults in the age group 80-89 (actual mortality: 3.2% versus predicted mortality: 5.6%, P = 0.08). After adjusting for covariates, the interaction term between age and predicted mortality (P = 0.0021) indicated that the relationship between predicted and actual mortality is significantly influenced by patient age.The NSQIP risk calculator appears to overestimate mortality and morbidity risk for elderly patients undergoing pancreatoduodenectomy. These predictions should be used with caution in preoperative goals-of-care discussions with patients aged 80 y and older.

Although primary tumor sidedness (PTS) has a known prognostic role in sporadic colorectal cancer (CRC), its role in Inflammatory Bowel Disease related CRC (IBD-CRC) is largely unknown. Thus, we aimed to evaluate the prognostic role of PTS in patients with IBD-CRC.All eligible patients with surgically treated, non-metastatic IBD-CRC were retrospectively identified from institutional databases at ten European and Asian academic centers. Long term endpoints included recurrence-free (RFS) and overall survival (OS). Multivariable Cox proportional hazard regression as well as propensity score analyses were performed to evaluate whether PTS was significantly associated with RFS and OS.A total of 213 patients were included in the analysis, of which 32.4% had right-sided (RS) tumors and 67.6% had left-sided (LS) tumors. PTS was not associated with OS and RFS even on univariable analysis (5-year OS for RS vs LS tumors was 68.0% vs 77.3%, respectively, p = 0.31; 5-year RFS for RS vs LS tumors was 62.8% vs 65.4%, respectively, p = 0.51). Similarly, PTS was not associated with OS and RFS on propensity score matched analysis (5-year OS for RS vs LS tumors was 82.9% vs 91.3%, p = 0.79; 5-year RFS for RS vs LS tumors was 85.1% vs 81.5%, p = 0.69). These results were maintained when OS and RFS were calculated in patients with RS vs LS tumors after excluding patients with rectal tumors (5-year OS for RS vs LS tumors was 68.0% vs 77.2%, respectively, p = 0.38; 5-year RFS for RS vs LS tumors was 62.8% vs 59.2%, respectively, p = 0.98).In contrast to sporadic CRC, PTS does not appear to have a prognostic role in IBD-CRC.

A major response to pre-hepatectomy chemotherapy has been associated with improved survival in patients who undergo resection of colorectal liver metastases (CRLM). However, the role of tumor biology, as exemplified by overall and codon-specific KRAS mutational status, in predicting response to chemotherapy is not well defined.Pathologic response was characterized as minor or major depending on the percentage of remnant viable cells (50% vs50%, respectively). Multivariable logistic regression was used to identify factors associated with major response.319 patients met inclusion criteria. 229 patients had a KRAS wild-type (wtKRAS) tumor and 90 harbored KRAS mutations (mutKRAS). A major pathologic response was more commonly noted in patients with wtKRAS compared to mutKRAS (48.5% vs 33.3%, P = 0.01) and wtKRAS status remained independently associated with a major response (P = 0.04). On a codon-specific level, major pathologic response occurred less frequently in those with codon 13 mutations (17.7%) compared to those with codon 12 (35.4%), and other KRAS mutations (33.3%). Importantly, codon 13 mutations were independently associated with minor pathologic response (P = 0.023).Patients with wtKRAS tumors appear to have the highest likelihood of experiencing a major response after preoperative chemotherapy. Future studies in "all-comer" cohorts are needed to confirm these findings and further investigate the response of codon 13 mutations.

To examine the prognostic impact of tumor laterality in colon cancer liver metastases (CLM) after stratifying by Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) mutational status.Although some studies have demonstrated that patients with CLM from a right sided (RS) primary cancer fare worse, others have found equivocal outcomes of patients with CLM with RS versus left-sided (LS) primary tumors. Importantly, recent evidence from unresectable metastatic CRC suggests that tumor laterality impacts prognosis only in those with wild-type tumors.Patients with rectal or transverse colon tumors and those with unknown KRAS mutational status were excluded from analysis. The prognostic impact of RS versus LS primary CRC was determined after stratifying by KRAS mutational status.277 patients had a RS (38.6%) and 441 (61.4%) had a LS tumor. Approximately one-third of tumors (28.1%) harbored KRAS mutations. In the entire cohort, RS was associated with worse 5-year overall survival (OS) compared with LS (39.4% vs 50.8%, P = 0.03) and remained significantly associated with worse OS in the multivariable analysis (hazard ratio 1.45, P = 0.04). In wild-type patients, a worse 5-year OS associated with a RS tumor was evident in univariable analysis (43.7% vs 55.5%, P = 0.02) and persisted in multivariable analysis (hazard ratio 1.49, P = 0.01). In contrast, among patients with KRAS mutated tumors, tumor laterality had no impact on 5-year OS, even in the univariable analysis (32.8% vs 34.0%, P = 0.38).This study demonstrated, for the first time, that the prognostic impact of primary tumor side differs according to KRAS mutational status. RS tumors were associated with worse survival only in patients with wild-type tumors.

Background The prognostic implication of mutant KRAS (mKRAS) among patients with primary disease in the rectum remains unknown. Methods From 2000 to 2018, patients undergoing hepatectomy for colorectal liver metastases at 10 collaborating international institutions with documented KRAS status were surveyed. Results A total of 834 (65.8%) patients with primary colon cancer and 434 (34.2%) patients with primary rectal cancer were included. In patients with primary colon cancer, mKRAS served as a reliable prognostic biomarker of poor overall survival (OS) (hazard ratio [HR]: 1.58, 95% CI 1.28-1.95) in the multivariable analysis. Although a trend towards significance was noted, mKRAS was not found to be an independent predictor of OS in patients with primary rectal tumors (HR 1.34, 95% CI 0.98-1.80). For colon cancer, the specific codon impacted in mKRAS appears to reflect underlying disease biology and oncologic outcomes, with codon 13 being associated with particularly poor OS in patients with left-sided tumors (codon 12, HR 1.56, 95% CI 1.22-1.99; codon 13, HR 2.10 95% CI 1.43-3.08;). Stratifying the rectal patient population by codon mutation did not confer prognostic significance following hepatectomy. Conclusions While the left-sided colonic disease is frequently grouped with rectal disease, our analysis suggests that there exist fundamental biologic differences that drive disparate outcomes. Although there was a trend toward significance of KRAS mutations for patients with primary rectal cancers, it failed to achieve statistical significance.

IMPORTANCE: The progression of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas to malignant disease is still poorly understood. Observational and surgical series have failed to provide comprehensive information. OBJECTIVE: To identify dynamic variables associated with the development of malignant neoplasms by combining pathological features with data from preoperative repeated observations. DESIGN, SETTING, AND PARTICIPANTS: The Crossover Observational Multicentric Study included a retrospective cohort of patients with branch-duct IPMNs (BD IPMNs) enrolled in a surveillance program from January 1, 2000, to December 31, 2019. Patients were enrolled from 5 referral centers: the Pancreas Institute, Verona, Italy; Seoul National University Hospital, Seoul, South Korea; Singapore General Hospital, Singapore; Johns Hopkins School of Medicine, Baltimore, Maryland; and University of Texas MD Anderson Cancer Center, Houston. Patients underwent a minimum of 12 months of preoperative surveillance (median, 37 [interquartile range (IQR), 20-68] months). MAIN OUTCOMES AND MEASURES: Dynamic variables associated with malignant disease were explored to estimate the presence of high-grade dysplasia (HGD) and invasive cancer at final pathological examination. RESULTS: A total of 292 patients were included in the analysis (137 women [46.9%] and 155 men [53.1%]; median age, 64 [IQR, 56-71] years). During surveillance, 27 patients (9.2%) developed a worrisome feature after 5 years, and 46 of 276 (16.7%) developed high-risk stigmata (HRS). At final pathological evaluation, 107 patients (36.6%) had HGD or invasive cancer, and 16 (5.5%) had IPMNs with concomitant pancreatic ductal adenocarcinoma. Rates of HGD and invasive cancer at pathological evaluation significantly differed between those without worrisome features and those developing HRS from a previous worrisome feature (9 [27.3%] vs 13 [61.9%]; P

The rates and routes of Helicobacter pylori transmission, in a high-prevalent country like Iran, with gastric cancer as the leading cause of male cancer mortality, are of great essence. Here, we have studied the H. pylori-associated risk factors and the likelihood of interspousal transmission.In a cohort of 686 young prewed couples, questionnaires were self-administered and serum samples were collected, for assessment of risk factors and H. pylori serostatus, at baseline and follow-up. Of the 475 H. pylori single- or double-seronegative couples, 201 returned for follow-up. The average follow-up duration was 2.2 (SD 0.6) years, with a total of 560.1 person-years. Logistic regression and Cox regression models were used to estimate the odds ratios (ORs) and hazard ratios (HRs).The risk of infection was higher in men than women (OR: 1.3, 95% CI: 1.0-1.8) and among metropolitan than rural residents (OR = 1.4, 95% CI: 1.1-1.9). It was also significantly higher among those with three (OR = 1.6, 95% CI: 1.1-2.2), and four or more siblings (OR = 1.4, 95% CI: 1.0-1.9), in reference to those with one or no siblings. Adult H. pylori acquisition occurred in 10.9% (27/247) of the seronegative participants. The risk of the acquisition was significantly associated with age (P value for trend=0,000). It was also significantly lower among participants who had various degrees of education as compared to illiterate subjects (HR = 0.2, 95% CI: 0.1-0.9). Nevertheless, our analysis did not find any evidence for interspousal transmission (HR = 1.0, 95% CI: 0.4-2.2).Whilst H. pylori acquisition was detected in the young adult Iranian population, our findings did not support interspousal transmission, as a mode of acquisition.

Background: Stomach cancer (SC) is one of the most common cancers in the world. Dietary risk factors of SC are not fully understood. This study aimed to investigate the association between macronutrient intakes and the risk of SC. Study design: A hospital-based case-control study. Methods: The data were obtained from a hospital-based case-control study conducted at the Cancer Institute of Iran from 2010 to 2012. Patients were 40 years or older and were diagnosed with SC in less than one year with no history of any cancers. On the other hand, the controls were healthy subjects who were caregivers or visitors of the patients. Demographic characteristics were collected using a structured questionnaire through face to face interviews by trained interviewers. Dietary data were obtained using a validated Diet History Questionnaire. The age and gender-adjusted odds ratios (ORs), as well as the adjusted ORs of age, gender, energy, education, smoking, and body mass index, were reported for continuous and tertiles of intakes. Results: Totally, 207 SC patients and 217 controls participated in this study. In the full adjusted model, after comparing the highest tertiles to the lowest ones, the intake of sucrose (OR: 2.94; 95% CI: 1.66-5.19; P-trend

Background The Stop the Bleed (STB) campaign was developed in part to educate the lay public about hemorrhage control techniques aimed at reducing preventable trauma deaths. Studies have shown this training increases bystanders’ confidence and willingness to provide aid. One high-risk group might be better solicited to take the course: individuals who have been a victim of previous trauma, as high rates of recidivism after trauma are well-established. Given this group's risk for recurrent injury, we evaluated their attitudes toward STB concepts. Methods We surveyed trauma patients admitted to 3 urban trauma centers in Baltimore from January 8, 2020 to March 14, 2020. The survey was terminated prematurely due to the COVID-19 pandemic. Trauma patients hospitalized on any inpatient unit were invited to complete the survey via an electronic tablet. The survey asked about demographics, prior exposure to life-threatening hemorrhage and first aid training, and willingness to help a person with major bleeding. The Johns Hopkins IRB approved waiver of consent for this study. Results Fifty-six patients completed the survey. The majority of respondents had been hospitalized before (92.9%) and had witnessed severe bleeding (60.7%). The majority had never taken a first aid course (60.7%) nor heard of STB (83.9%). Most respondents would be willing to help someone with severe bleeding form a car crash (98.2%) or gunshot wound (94.6%). Conclusions Most patients admitted for trauma had not heard about Stop the Bleed, but stated willingness to respond to someone injured with major bleeding. Focusing STB education on individuals at high-risk for trauma recidivism may be particularly effective in spreading the message and skills of STB.

Ethnopharmacological relevance Launaea acanthodes (Boiss.) O. Kuntze is native to semiarid regions of central Iran, traditionally used in the treatment of numerous disorders including diabetes. Aim of the study The current study aimed to explore hypoglycemic activity of Launaea acanthodes extract in streptozotocin-induced diabetic rats. Furthermore, gene expression study was carried out to examine expression levels of key glucose metabolism-related genes. Methods For in vitro study, Folin-Ciocalteus, DPPH and aluminum chloride colorimetric assays were used to determine the total phenolic content, antioxidant capacity and total flavonoid content of extracts, respectively. For in vivo study, streptozotocin-induced diabetic Wistar rats were orally administered with metformin (50 mg/kg) and various doses of extracts (100, 200 and 400 mg/kg body weight) for 28 days. Fasting blood glucose, body weight, food and water intake were assessed during the course of treatment. At the end of the intervention, oral glucose tolerance test (OGTT), lipid profile and glycated hemoglobin (HbA1c) were evaluated. Furthermore, functional liver enzymes, oxidative stress markers and histopathology of pancreas were examined. Lastly, quantitative real time polymerase chain reaction (qRT-PCR) was applied to explore the mRNA levels of genes relevant to glucose metabolism in the pancreas and liver tissues of diabetic rats. Results Based on the in vitro results, the hydroalcoholic extract revealed potential radical scavenging activity and contained highest amount of phenolic and flavonoid. The in vivo results demonstrated that the extract lowered fasting blood glucose level, increased the body weight, restored the alterations in the levels of water and food intake, attenuated HbA1c, improved lipid profile and ameliorated the OGTT in diabetic rats. The extract administration alleviated the histopathological changes in the pancreas, suppressed malondialdehyde (MDA) level and further restored attenuated levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) in diabetic rats. Analysis of real time PCR data showed that extract administration reversed the expression levels of hepatic glucokinase (GK), phosphenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). Meanwhile, the extract upregulated the expression level of glucose transporter-2 (GLUT-2) and pancreatic-duodenal homeobox (PDX-1) in diabetic rats. Conclusion Collectively, the results demonstrate that Launaea acanthodes hydroalcoholic extract exerts hypoglycemic effect possibly via regulating key enzymes of glucose metabolism and ameliorating pancreatic dysfunction through its antioxidant properties.

Background Combined hepatic resection and radiofrequency ablation (resection-RFA) is a widely accepted multidisciplinary treatment for unresectable colorectal cancer liver metastases. Worse prognosis after resection-RFA is correlated to tumor morphology, although unfavorable morphology is inherent to this patient cohort. This study aimed to select patients who may or may not benefit from resection-RFA with the aid of tumor biology. Method Data from 485 patients who underwent curative hepatectomy with or without concurrent RFA were retrospectively collected and analyzed. Clinicopathologic characteristics, predictors of overall survival (OS), and OS of patients stratified by tumor biology in resection-RFA were analyzed. Results Combined resection-RFA was performed in 86 patients (17.7%) and a standalone resection in 399 patients. Baseline patients' characteristics of the resection-RFA group were significantly different in terms of median number of tumors (5 versus 2) and bilobar distribution (84.9% versus 29.1%) from those of the resection-only group. Multivariate analysis identified four independent predictors of decreased OS in the resection-RFA group. Three were related to tumor biology: primary tumor nodal metastases (hazard ratio [HR], 2.32; 95% confidence interval (95% CI), 1.16-4.64], Kirsten rat sarcoma viral oncogene homolog mutation (HR, 2.64; 95% CI, 1.36-5.14), and preoperative high carcinoembryonic antigen (HR, 2.33; 95% CI, 1.13-4.81), and one related to tumor morphology–ablated lesions ≥3 (HR, 2.05; 95% CI, 1.41-3.80; P = 0.023). To examine the prognostic influence of tumor biology, the resection-RFA group was stratified into two groups by number of predictors related to tumor biology (low risk: 0-1 risk factors; n = 56 and high risk: 2-3 risk factors; n = 30). Median OS of the low risk, high risk, and resection-alone groups were 61.8, 20.7, and 75.3 mo, respectively. The 5-y OS rate was similar between the low risk and resection-alone group (52.7% versus 58.7%, respectively; P = 0.323). Conclusions Patients with low-risk tumors undergoing a combined resection-RFA approach had roughly comparable OS to those who only underwent resection, irrespective of advanced tumor morphology. Combined resection-RFA procedures might be of value to these patients.

There is limited evidence characterizing the impact of glycemic alterations on short-term outcomes among patients undergoing resection of colorectal liver metastases (CRLM).Hyperglycemia was defined as a glucose value125 mg/dl according to WHO definition. The impact of early postoperative hyperglycemia on short-term postoperative outcomes was assessed.The mean postoperative glucose value was 128 mg/dl; 30 (9.8 %) patients had normal fasting glucose (100 mg/dl), 106 patients had glucose intolerance (100-125 mg/dl), and 170 (55.5 %) patients had hyperglycemia (125 mg/dl). A postoperative complication occurred in 101 patients (morbidity, 33.1 %); among patients who experienced a complication, an infectious complication was most common (38.6 %). After controlling for clinical factors, patients with hyperglycemia had an increased risk of overall complications [odds ratio (OR) 4.11; 95 % confidence interval (CI) 1.96-8.62, P 0.001]. This was the case for both patients with and without diabetes (P 0.05). Patients with hyperglycemia on the day of surgery were also at an increased risk of infections [OR 9.17; 95 % CI 2.26-37.13, P = 0.002] and had a longer hospital stay (normal glucose, 4 days vs. glucose 100-125 mg/dl, 4 days vs. glucose125 mg/dl, 5 days, P 0.001).Early postoperative hyperglycemia was associated with adverse outcomes in patients with and without diabetes who underwent resection of CRLM. Perioperative glucose evaluation may be an important quality target.

Obese patients may present with metabolic abnormalities that impact liver regeneration. We sought to assess the impact of body mass index (BMI) on liver volume regeneration index (RI) and kinetic growth rate (KGR) among patients undergoing liver resection.The study included 102 patients undergoing major hepatectomy (≥3 segments) between July 2004 and April 2015 and stratified the patients by preoperative BMI, number of segments resected, and postoperative remnant liver volume (RLVp) to total liver volume ratio. Resected volume at operation was subtracted from total liver volume to calculate postoperative RLVp. RI was defined as the relative increase in RLV within 2 months [(RLV2m-RLVp)/RLVp] and 7 months [(RLV7m-RLVp)/RLVp] postoperatively; KGR was calculated as RI divided by time postoperatively (weeks).Median patient age was 59.6 years (interquartile range 48.1-68.7 years), and most patients were men (52.0%). Liver failure was associated with the KGR at 2 months (KGR2m) and was greater among patients with KGR2m2.5% per week (KGR2.5%, 18.5% vs KGR ≥ 2.5%, 4.6%; P = .04). Although RI and KGR within 2 and 7 months postoperatively were similar among all patients, after excluding patients with fibrosis, obese (0.42% per week) and overweight patients (0.29% per week) had lesser KGR2-7m compared with patients of normal BMI (0.82% per week; P .05). Additionally, risk of a major complication was greatest among obese patients (normal weight, 8.1% vs overweight, 12.9% vs obese, 29.4%; P = .04).BMI did not impact liver regeneration during the first 2 months. In contrast, KGR per week between 2 and 7 months postoperatively was less among overweight and obese patients.

Background and Objectives While the prognostic role of KRAS status after resection of CRLM has been previously explored, the importance of KRAS status relative to the receipt of preoperative chemotherapy remains largely unknown. Methods A total of 430 patients who underwent curative-intent surgery for CRLM between 2000 and 2015 and who had available KRAS genotype data were identified. Data regarding KRAS mutation status, receipt of preoperative chemotherapy, and overall survival (OS) were assessed using univariable and multivariable analyses. Results Median patient age was 58 years (IQR, 50.4–66.4 years). A total of 258 patients (60.0%) received preoperative chemotherapy, while 172 (40.0%) had upfront surgery. Median and 5-year OS in the entire cohort was 65.1 months and 53.2%, respectively. KRAS mutation was associated with a worse 5-year OS compared with wild-type tumors (HR 1.41; P = 0.042). After stratifying by the receipt of preoperative chemotherapy, the prognostic value of KRAS mutation only persisted among patients who had received preoperative chemotherapy (HR 1.67; P = 0.012). In contrast, KRAS mutation status had no impact on OS among patients who had not received preoperative chemotherapy (P = 0.597). Conclusions KRAS mutation status was an independent predictor of OS among patients undergoing liver resection of CRLM. However, after stratifying by receipt of preoperative chemotherapy, KRAS was informative relative to prognosis only among patients who received preoperative chemotherapy. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

Background Investigations regarding the impact of tumor biology after surgical management of colorectal liver metastasis have focused largely on overall survival. We investigated the impact of codon-specific KRAS mutations on the rates and patterns of recurrence in patients after surgery for colorectal liver metastasis (CRLM). Methods All patients who underwent curative-intent surgery for CRLM between 2002 and 2015 at Johns Hopkins who had available data on KRAS mutation status were identified. Clinico-pathologic data, recurrence patterns, and recurrence-free survival (RFS) were assessed using univariable and multivariable analyses. Results A total of 512 patients underwent resection only (83.2%) or resection plus radiofrequency ablation (16.8%). Although 5-year overall survival was 64.6%, 284 (55.5%) patients recurred with a median RFS time of 18.1 months. The liver was the initial recurrence site for 181 patients, whereas extrahepatic recurrence was observed in 162 patients. Among patients with an extrahepatic recurrence, 102 (63%) had a lung recurrence. Although overall KRAS mutation was not associated with overall RFS (P = 0.186), it was independently associated with a worse extrahepatic (P = 0.004) and lung RFS (P = 0.007). Among patients with known KRAS codon-specific mutations, patients with codon 13 KRAS mutation had a worse 5-year extrahepatic RFS (P = 0.01), whereas codon 12 mutations were not associated with extrahepatic (P = 0.11) or lung-specific recurrence rate (P = 0.24). On multivariable analysis, only codon 13 mutation independently predicted worse overall extrahepatic RFS (P = 0.004) and lung-specific RFS (P = 0.023). Conclusions Among patients undergoing resection of CRLM, overall KRAS mutation was not associated with RFS. KRAS codon 13 mutations, but not codon 12 mutations, were associated with a higher risk for overall extrahepatic recurrence and lung-specific recurrence. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2698-2707. © 2016 American Cancer Society.

Although the American Joint Committee on Cancer (AJCC) classification is the most accepted lymph node (LN) staging system for gallbladder adenocarcinoma (GBA), other LN prognostic schemes have been proposed. This study sought to define the performance of the AJCC LN staging system relative to the number of metastatic LNs (NMLN), the log odds of metastatic LN (LODDS), and the LN ratio (LNR). Patients who underwent curative-intent resection for GBA between 2000 and 2015 were identified from a multi-institutional database. The prognostic performance of various LN staging systems was compared by Harrell’s C and the Akaike information criterion (AIC). Altogether, 214 patients with a median age of 66.7 years (interquartile range [IQR] 56.5–73.1) were identified. A total of 1334 LNs were retrieved, with a median of 4 (IQR 2–8) LNs per patient. Patients with LN metastasis had an increased risk of death (hazard ratio [HR] 1.87; 95 % confidence interval [CI] 1.24–2.82; P = 0.003) and recurrence (HR 2.28; 95 % CI 1.37–3.80; P = 0.002). In the entire cohort, LNR, analyzed as either a continuous scale (C-index, 0.603; AIC, 803.5) or a discrete scale (C-index, 0.609; AIC, 802.2), provided better prognostic discrimination. Among the patients with four or more LNs examined, LODDS (C-index, 0.621; AIC, 363.8) had the best performance versus LNR (C-index, 0.615; AIC, 368.7), AJCC LN staging system (C-index, 0.601; AIC, 373.4), and NMLN (C-index, 0.613; AIC, 369.5). Both LODDS and LNR performed better than the AJCC LN staging system. Among the patients who had four or more LNs examined, LODDS performed better than LNR. Both LODDS and LNR should be incorporated into the AJCC LN staging system for GBA.

Introduction It is currently unknown whether formal research training has an influence on academic advancement in plastic surgery. The purpose of this study was to determine whether formal research training was associated with higher research productivity, academic rank, and procurement of extramural National Institutes of Health (NIH) funding in plastic surgery, comparing academic surgeons who completed said research training with those without. Methods This was a cross-sectional study of full-time academic plastic surgeons in the United States. The main predictor variable was formal research training, defined as completion of a postdoctoral research fellowship or attainment of a Doctor of Philosophy (PhD). The primary outcome was scientific productivity measured by the Hirsh-index ( h -index, the number of publications, h that have at least h citations each). The secondary outcomes were academic rank and NIH funding. Descriptive, bivariate, and multiple regression statistics were computed. Results A total of 607 academic surgeons were identified from 94 Accreditation Council for Graduate Medical Education-accredited plastic surgery training programs. In all, 179 (29.5%) surgeons completed formal research training. The mean h -index was 11.7 ± 9.9. And, 58 (9.6%) surgeons successfully procured NIH funding. The distribution of academic rank was the following: endowed professor (5.4%), professor (23.9%), associate professor (23.4%), assistant professor (46.0%), and instructor (1.3%). In a multiple regression analysis, completion of formal research training was significantly predictive of a higher h -index and successful procurement of NIH funding. Conclusion Current evidence demonstrates that formal research training is associated with higher scientific productivity and increased likelihood of future NIH funding.

The impact of phosphorus as well as glycemic alterations on liver regeneration has not been directly examined. We sought to determine the impact of phosphorus and glucose on liver regeneration after major hepatectomy. Early and late liver regeneration index was defined as the relative increase of liver volume (RLV) within 2[(RLV2m-RLVp)/RLVp] and 7 months[(RLV7m-RLVp)/RLVp] following surgery. The association of perioperative metabolic factors, liver regeneration, and outcomes was assessed. On postoperative day 2, 50 (52.6 %) patients had a low phosphorus level (≤2.4 mg/dl), while 45 (47.4 %) had a normal/high phosphorus level (>2.4 mg/dl). Despite comparable clinicopathologic characteristics (all P > 0.05) and RLV/TLV at surgery (P = 0.84), regeneration index within 2 months was lower in the normal/high phosphorus group (P = 0.01) with these patients having increased risk for postoperative liver failure (P = 0.01). The inhibition of liver regeneration persisted at 7 months (P = 0.007) and was associated with a worse survival (P = 0.02). Preoperative hypoglycemia was associated only with a lower early regeneration index (P = 0.02). Normal/high phosphorus was associated with inhibition of early and late liver regeneration, as well as with an increased risk of liver failure and worse long-term outcomes. Immediate preoperative hypoglycemia was associated with a lower early volumetric gain. Metabolic factors may represent early indicators of liver failure that could identify patients at increased risk for worse outcomes.

Cervicare™ is a poly-herbal preparation comprised of a combination of 6 plants; most have demonstrated antimicrobial and anticancer properties in preclinical studies. The effect of the ethanol and aqueous extracts of Cervicare™ on cell proliferation and apoptosis using cervical cancer HeLa and CaSki cells was investigated for the first time in the present study. MTT assay results showed that Cervicare™ extracts exerted time- and dose-dependent inhibition of cell viability. The hallmark properties of apoptosis like cell shrinkage and cytoplasmic condensation were observed using an inverted phase contrast microscope, ethidium bromide/acridine orange and Hoechst 33342/propidium iodide fluorescent staining methods. Furthermore, our results demonstrated that Cervicare™ extracts induced apoptosis in HeLa and CaSki cells by ROS generation and mitochondrial depolarization in a concentration dependent manner. The results showed that Cervicare™ extracts were capable of suppressing cell migration and inhibiting colony formation in a dose-dependent manner. Moreover, western blot analysis demonstrated the involvement of a mitochondria-dependent apoptosis pathway in the apoptosis inducing activity of Cervicare™ ethanol extract in HeLa cells. GC-MS analysis of the ethanolic extract afforded the identification of 40 substances, showing that it was primarily composed of anti-cancerous compounds such as xanthorrhizol (60.40%), octacosane (9.93%) and squalene (1.24%). Together, these results point out the Cervicare™ mediated inhibition of HeLa cell growth via induction of apoptosis and that it may be a potential anticancer agent which deserves further investigation.

The main component that contributes to the high value of pineapple is bromelain which is a proteolytic enzyme and has been scientifically identified as a therapeutic agent. This study was conducted to obtain high quantity of bromelain from pineapple and to investigate the anticarcinogenic activity of fresh pineapple juices against A2780 ovarian and HT29 colon cancer cell lines. It was found that homogenization, ultrafiltration, precipitation and dialysis contributed to heavy loss of bromelain. Therefore, fresh pineapple juices from the flesh (PJ-F), core (PJ-C) and stem (PJ-S) were selected as a source of crude bromelain. Various bromelain concentrations of PJ-F, PJ-C and PJ-S (1 μg/ml, 10 μg/ml, 100 μg/ml and 1000 μg/ml) were exposed to the cancer cells and the cell viability was determined using Methylthiazol Tetrazolium Assay (MTT assay) after 24, 48 and 72 h. Besides, IC50 values were measured. Using normal cell (HSF1184) comparison, it was found that a 100 μg/ml concentration of bromelain would efficiently inhibit the cancer cells without affecting the surrounding normal cells. Microscopic examinations were carried out to elucidate the modes of cell death on the basis of morphological alterations using florescent and inverted phase contrast microscopes. Furthermore, the colony forming abilities of fresh pineapple juices on A2780 and HT29 cells were examined. The results demonstrated that PJ-F, PJ-C and PJ-S effectively suppressed the colony formation in cancer cells. The findings suggest that PJ-F, PJ-C and PJ-S may have the potential to induce anticarcinogenic effects through an apoptosis to A2780 and HT29 cells in vitro.

Varying definitions of resection margin clearance are currently employed among patients with colorectal cancer liver metastases (CRLM). Specifically, a microscopically positive margin (R1) has alternatively been equated with an involved margin (margin width = 0 mm) or a margin width 1 mm. Consequently, patients with a margin width of 0-1 mm (sub-mm) are inconsistently classified in either the R0 or R1 categories, thus obscuring the prognostic implications of sub-mm margins.Six hundred thirty-three patients who underwent resection of CRLM were identified. Both R1 definitions were alternatively employed and multivariable analysis was used to determine the predictive power of each definition, as well as the prognostic implications of a sub-mm margin.Five hundred thirty-nine (85.2%) patients had a margin width ≥ 1 mm, 42 had a sub-mm margin width, and 52 had an involved margin (0 mm). A margin width ≥ 1 mm was associated with improved survival vs. a sub-mm margin (65 vs. 36 months; P = 0.03) or an involved margin (65 vs. 33 months; P 0.001). No significant difference in survival was detected between patients with involved vs. sub-mm margins (P = 0.31). A sub-mm margin and an involved margin were both independent predictors of worse OS (HR 1.66, 1.04-2.67; P = 0.04, and HR 2.14, 1.46-3.16; P 0.001, respectively) in multivariable analysis. Importantly, after combining the two definitions, patients with either an involved margin or a sub-mm margin were associated with worse OS in multivariable analysis (HR 1.94, 1.41-2.65; P 0.001).Patients with involved or sub-mm margins demonstrated a similar inferior OS vs. patients with a margin width 1 mm. Consequently, a uniform definition of R1 as a margin width 1 mm should perhaps be employed by future studies.

The long-term impact of transfusions with packed red blood cells (PRBC) among patients undergoing hepatopancreaticobiliary (HPB) surgery remains ill-defined. We sought to determine the impact of overall blood utilization, as well as a restrictive transfusion strategy, on long-term outcomes among patients undergoing an HPB resection for a malignancy. Data on overall blood utilization and hemoglobin (Hb) levels that triggered a transfusion were obtained for patients with cancer undergoing pancreas or liver surgery between 2009 and 2013. Risk-adjusted recurrence-free (RFS) and overall survival (OS) were assessed based on receipt of PRBC and whether the patient received a transfusion using a restrictive transfusion strategy (intraoperative: Hb

Metastatic disease to the regional lymph node (LN) is a strong predictor of worse long-term outcome after curative-intent resection of intrahepatic cholangiocarcinoma (ICC). The objectives of this study were to assess the prognostic performance of American Joint Committee on Cancer (AJCC)/International Union Against Cancer, 7th edition, N stage, LN ratio (LNR), and log odds of metastatic LN (LODDS) staging criteria in patients with ICC. The surveillance, epidemiology, and end results cancer registry was queried to identify 749 patients who underwent surgical resection of ICC during 1988–2011. The Kaplan–Meier method and Cox proportional hazards regression models were used to analyze survival. The relative discriminative abilities of the different LN staging systems were assessed by the Harrell concordance index (c statistic). Of the 749 patients, 477 (63.7 %) had no LN metastasis, while 272 (36.3 %) had LN metastasis. Patients with LN metastasis had an increased risk of death (hazard ratio 2.42, 95 % confidence interval 1.98–2.95; P

Background and Objectives Several lymph node (LN) staging/scoring systems have been proposed to stratify the prognosis of patients with gallbladder adenocarcinoma (GBA). We sought to define the prognostic performance of the most commonly utilized LN staging/scoring systems including AJCC/UICC N stage, lymph node ratio (LNR), log odds (LODDS), and N score, among patients with GBA. Method Between 2004 and 2010, 1,124 patients with GBA were identified from the Surveillance Epidemiology and End Results (SEER) database. The discriminative ability of each LN staging/scoring system was assessed using the Akaike's Information Criterion (AIC) and the Harrell's concordance index. Results When assessed using categorical values, LNR had a modest, improved ability to discriminate patients with regard to prognosis (C-index: 0.615; AIC: 2118.2) compared with AJCC/UICC N stage or N score and a prognostic discrimination comparable to LODDS. Among patients who had a total number of LN examined (TNLE) of 1 or 2, all the staging/scoring systems performed comparably. In contrast, among patients who had ≥4 TNLE, LODDS performed the best (C-index: 0.613; AIC: 303.2). Conclusion The performance of the different LN staging/scoring systems varied based on the TNLE. In particular, for patients who had ≥4 TNLE, LODDS out-performed the other staging/scoring systems. J. Surg. Oncol. 2015 111:299–305. © 2014 Wiley Periodicals, Inc.

Background and Objectives Potential differences in presentation and outcome of patients with gastric cardia adenocarcinoma (GCA) and non-cardia adenocarcinoma may exist. The aim of the present study was to compare the clinicopathological characteristics and the prognosis of GCA versus non-cardia adenocarcinoma. Method Patients with gastric adenocarcinoma who underwent gastric resection between 2000–2012 were identified. Clinicopathological characteristics and outcomes were analyzed based on tumor site using a 1:2 matched-control, as well as a multivariable Cox model. Results Among 743 patients, 80 (10.7%) patients were diagnosed with GCA. Patients with GCA were more likely to have intestinal tumor type (GCA: 80.4% versus non-cardia: 64.2%, P = 0.04) or advanced AJCC T stage tumors (GCA 71.8% versus non-cardia 59.2%, P = 0.03). GCA patients more likely underwent a total gastrectomy (GCA: 85.7% vs. non-cardia: 39.8%) and had a longer length-of-stay (GCA: 10 days vs. non-cardia: 8 days) (both P

Background and Objectives Data on outcomes after liver-directed therapy for intrahepatic cholangiocarcinoma (ICC) are limited due to the rarity of the disease. We sought to define overall utilization and temporal trends of liver-directed therapy for ICC. Methods We identified 5,388 patients with ICC using the Surveillance Epidemiology and End Results (SEER) database between 1983 and 2010. Patients were characterized based on the type of liver-directed therapy received: surgical resection, ablation therapy, and radiation therapy. Results The majority of patients did not undergo liver-directed therapy (n = 4,156, 77.1%). Among those undergoing liver-directed therapy, surgical resection was most commonly performed (n = 672, 54.5%) and its utilization increased threefold over time (P = 0.001). The use of ablation therapy alone was used in 5.2% of patients and increased nearly sixfold over time (P = 0.39) whereas the use of radiation therapy alone decreased by nearly half (P 5 cm). Conclusion There was a moderate improvement in overall survival in patients with ICC between 1983 and 2010. The majority of patients with ICC are not undergoing liver-directed therapy. Among those who do undergo liver-directed therapy, the use of ablation therapy and surgery are increasing with nearly three in five patients undergoing resection. J. Surg. Oncol. 2014; 110:163–170. © 2014 Wiley Periodicals, Inc.

To evaluate the impact of transfused packed red blood cell (PRBC) age on perioperative morbidity among patients undergoing major gastrointestinal surgery.Patients undergoing major surgery often receive PRBC transfusions. The effect of PRBC age (ie, storage duration before transfusion) on perioperative surgical outcomes remains poorly defined.In this study, 1365 patients were identified who underwent a hepato-pancreatic or colorectal resection and received ≥1 unit of PRBCs between 2009 and 2014 at the Johns Hopkins Hospital. Data regarding the storage duration of PRBCs, clinicopathologic characteristics, and perioperative outcomes were obtained and analyzed. Multivariable modified Poisson regression analyses were performed to assess the effect of PRBC age on perioperative morbidity.A total of 5901 PRBC units were transfused for a median of 2 (interquartile range 2-4) units transfused per patient. In all, 936 (68.6%) patients received only units of blood that had been stored for less than 35 days ("fresh" blood), whereas 429 (31.4%) patients received at least 1 unit of PRBC that had been stored for ≥35 days ("older" blood). Overall postoperative morbidity was 32.8%. The incidence of postoperative complications (42.7% vs 28.3%) was higher among patients who received "older" vs "fresh" blood (P0.001). After adjusting for confounders on multivariable analysis, transfusion of "older" blood remained independently associated with an increased risk of perioperative morbidity (Relative Risk 1.20, P = 0.03).The use of "older" blood was an independent predictor of postoperative morbidity among patients undergoing hepato-pancreatic or colorectal procedures. Transfusion of "older" blood products may contribute to a higher risk of postoperative complications.

Given the increasing number of elderly and comorbid patients undergoing surgery, there is increased interest in preoperatively identifying patients at high risk of morbidity and mortality following liver resection. We sought to develop and validate the use of a frailty index (FI) to predict poor postoperative outcomes following liver surgery. Patients undergoing a liver resection were identified using the National Surgical Quality Improvement Program Hepatectomy-targeted database for 2014 and randomized into a training or validation cohort. Multivariable logistic regression analysis was performed to develop a revised frailty index (rFI) to predict adverse postoperative clinical outcomes. Leave one out cross-validation was performed to validate the proposed rFI. A total of 2714 patients were identified who met the inclusion criteria. Postoperatively, 826 patients (30.4%) developed a postoperative complication, while 39 patients died within 30 days of surgery. Five preoperative variables (ASA class, BMI, serum albumin, hematocrit, underlying pathology, and type of liver resection) were used to develop the rFI. The rFI demonstrated good discrimination (AUROC = 0.68) and outperformed the previously proposed modified frailty index (mFI; AUROC = 0.53, p

BACKGROUND Resection is the most effective treatment for HCC. However, postoperative morbidity is common and its impact on long-term oncological outcome remains unclear. METHODS Long-term outcomes of 774 patients who underwent curative resection for early stage HCC at Johns Hopkins Hospital and Toranomon Hospital were investigated after stratifying by the development of postoperative overall and infectious complications. RESULTS A minor or major postoperative complication developed in 281 and 65 patients, respectively, while postoperative mortality was 1.3% (n = 10). The 5-year cumulative recurrence and overall survival(OS) rates were 57.2% and 76.4%, respectively. Overall postoperative complications independently predicted worse OS in multivariable analysis (HR = 1.42, P = 0.021). Complication severity did not correlate with OS (P > 0.05). While infectious complications were not independent predictors of OS, the combination of blood transfusion and infectious complications led to significantly worse OS (66.3% vs. 44.9%, P = 0.008). Postoperative complications also correlated with increased recurrence risk, but only in patients with non-cirrhotic parenchyma (55.0% vs. 47.7%, P = 0.035) or non-viral hepatitis (55.6% vs. 44.4%, P = 0.002). CONCLUSIONS Post-operative morbidity independently predicted poor OS following hepatectomy for early stage HCC. A similar effect on recurrence was noted only in patients with favorable etiopathologic factors. Finally, the combination of peri-operative transfusion and subsequent infectious complications was associated with a synergistic negative effect on prognosis.

The impact of prehepatectomy carcinoembryonic antigen (CEA) levels in the era of modern chemotherapy and expanded surgical indications for colorectal liver metastasis (CRLM) remains not well defined.484 patients were identified and divided into two groups by surgical time period (group 1: 2000-2007 vs. group 2: 2008-2015). The prognostic significance of pre-hepatectomy CEA was determined by assessing the HRs associated with various cut-off levels ranging from 5 to 200 ng/mL.Median CRLM number was comparable in both groups (group 1: 2 vs. group 2: 2, P = 0.504). Bilobar disease was more frequent in group 2 (30.1% vs. 42.5%, P = 0.006). The administration of modern chemotherapy and/or biologic agents increased over time (49.5% vs. 67.9%, P 0.001). Preoperative CEA independently predicted OS in group 1, even with a cut-off as low as5 ng/mL. However, in group 2 it predicted recurrence and survival only after exceeding 70 and 50 ng/mL, respectively. Of note, in group 2, CEA was strongly associated with survival when CEA levels exceeded 70 ng/mL (HR 4.84).While pre-hepatectomy CEA level may still have prognostic utility in CRLM resection, the optimal cut-off value has increased in the era of modern chemotherapy.

Post-operative bile leak (BL) and post hepatectomy liver failure (PHLF) are the major potential sources of morbidity among patients undergoing liver resection. We sought to define the incidence of BL and PHLF among a large cohort of patients, as well as examine the prognostic impact of model for end-stage liver disease (MELD) and albumin-bilirubin (ALBI) scores to predict these short-term outcomes. Patients who underwent a hepatectomy between January 1, 2014 and December 31, 2014 were identified using the National Surgical Quality Improvement Program (NSQIP) liver-targeted database. Risk factors for BL and PHLF were identified using multivariable logistic regression. Among the 3064 patients identified, median age was 60 years (IQR 50–68). Most patients underwent surgery (78.9 %) for malignant lesions. Post-operatively, 250 (8.5 %) patients experienced a BL while PHLF occurred in 149 cases (4.9 %). Both MELD (MELD