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Background: The oncological efficacy of laparoscopic surgery for advanced gastric cancer (AGC) has been evaluated by several randomized trials. However, the inclusion of earlier-stage disease was a limitation in previous studies. Methods: Patients with cT3-4 gastric cancer, determined by surgical staging to minimize migration of earlier stages, treated at a tertiary cancer center from 2009 to 2018 were included. Based on the surgical approach, the patients were divided into two groups: the laparoscopic gastrectomy (LG) and the open gastrectomy (OG) and matched for age, sex, macroscopic appearance (type 4 or non-type 4), body mass index, estimated tumor size, clinical stage T3'T4, clinical N stage, pathologic T stage (T3 or T4), and type of surgery (total or distal gastrectomy). Results: 588 patients (221 LG, 367 OG) were included in the analysis. After 1:1 propensity-score matching, 386 patients (193 LG, 193 OG) were assigned for analysis. In the LG group, operation time was longer with lower blood loss. The incidence of postoperative complications (≥ grade III) did not differ significantly between the groups (OG: 8.3%, vs. LG: 9.3%). Overall survival (OS) was longer in the LG group (5-year OS: 79.3 vs. 73% HR 0.66, 95% CI 0.44–0.99, P = 0.0497). Relapse-free survival (RFS) did not show a statistical difference (5-year RFS: 69.5 vs. 68.7 HR 0.88, 95% CI 0.62–1.26, P = 0.487). Subgroup analysis for OS also demonstrated equivalent outcomes. Conclusion: LG demonstrates comparable safety and efficacy to OG for advanced gastric cancer at surgical staging, with similar rates of severe complications and long-term oncological outcomes. Further research is needed to validate these findings, particularly for total gastrectomy and for patients from Western populations. [ABSTRACT FROM AUTHOR]

Introduction: Pancreatoduodenectomy (PD) for pancreatic adenocarcinoma (PDAC) presents a significant challenge owing to its aggressive nature. Traditionally performed as open surgery, the advent of minimally invasive surgery (MIS) including laparoscopic and robotic techniques, offers a potential alternative. This study assessed the use and outcomes of MIS and open PD for PDAC treatment. Methods: We analyzed ACS-NSQIP data (2015–2021) using regression models to compare patient outcomes across open PD, MIS PD, and conversions from MIS to open (MIS-O). Results: Of 19,812 PDAC patients, 1,293 (6.53%) underwent MIS, 18,116 (91.44%) underwent open PD, and 403 (2.03%) underwent MIS converted to open PD (MIS-O). The MIS rate increased from 6.1% to 9.2%. Black patients had a higher MIS-O rate (RR, 1.55; p = 0.025). Open PD was associated with more severe conditions (ASA ≥ III, malnutrition) and prior radiation therapy. MIS patients more often had neoadjuvant chemotherapy. Complex procedures, such as vein resection, favored open PD. Need for arterial resection was associated with MIS-O (RR, 2.11; p = 0.012), and operative time was significantly associated with MIS (OR: 4.32, 95% CI: 3.43–5.43, p-value: < 0.001) No differences in the overall morbidity or 30-day mortality were observed. MIS led to shorter stays but higher risks of reoperation and pulmonary embolism. MIS-O increased the delayed gastric emptying rate (RR, 1.79; p < 0.001). Conclusion: During 2015–2021, an increasing number of patients with PDAC are undergoing MIS PD. Morbidity and mortality did not differ between open and MIS PD. MIS was performed more frequently in patients with better nutritional status and lower ASA, or when vascular resection was not anticipated. In well selected patients, short-term outcomes of MIS and open PD seem similar. [ABSTRACT FROM AUTHOR]

Background: This study investigated the association between vitamins intakes and risk of gastric cancer (GC) among Iranian population. Methods: In this hospital-based case-control study, 178 pathologically confirmed GC patients and 276 healthy controls were interviewed to answer a valid diet history questionnaire. Unconditional logistic regression, in which potential confounders were taken into account, was applied to determine the association of vitamin intakes and odds of GC in total population and in stratums of body mass index (BMI), helicobacter pylori (H-pylori) infection, and smoking. Results: GC was directly associated with vitamin D (OR 1.59; CI 95% 1.07, 2.36) and cobalamin (OR 1.25; CI 95% 1.08, 1.44). Thiamin (OR 0.50; 95%CI 0.30, 0.83), pantothenic acid (OR 0.71; 95%CI 0.58, 0.87), folate (OR 0.99; 95%CI 0.99, 0.99) and vitamin E (OR 0.98; 95%CI 0.96, 0.99) were inversely associated with GC. In 231 H-pylori infected participants, consumption of thiamin (OR 0.3; 95% CI 0.59, 0.86), pyridoxine (OR 0.52; 95%CI 0.31, 0.85), and folate (OR 0.99; 95%CI 0.99, 0.99) reduced GC risk. In H-pylori negative participants, only vitamin E (OR 0.96; 95%CI 0.93, 0.99) reduced the risk and vitamin D (OR 1.99; 95%CI 1.18, 3.36), riboflavin (OR 1.91; 95%CI 1.37, 2.66), pantothenic acid (OR 1.34; 95%CI 1.13, 1.64), biotin (OR 1.03; 95%CI 1.01, 1.05), and cobalamin (OR 1.36; 95%CI 1.13, 1.64) increased the risk. In BMI stratums, only vitamin D (OR 1.81; 95%CI 1.07, 3.08) was associated with the risk of GC among normal weight participants. Vitamin E was associated with lower risk of GC in ever smokers (OR 0.97; 95%CI 0.95, 0.99) and thiamin (OR 0.41; 95%CI 0.19, 0.86) and niacin (OR 0.93; 95%CI 0.87, 0.99) were associated with lower risk in never smokers. Positive associations were observed by increasing vitamin D (OR 2.08; 95%CI 1.12, 3.85) and cobalamin (OR 1.33; 95%CI 1.08, 1.65) in never smokers. Conclusion: This study provided support for a possible protective effect of vitamin E, thiamin, pantothenic acid, and folate on GC risk. Vitamin D and cobalamin intake increased the risk. [ABSTRACT FROM AUTHOR]

Objectives: To identify predictors, patterns, and timing of recurrence after resection of invasive carcinomas arising in association with an IPMN. Background: Postoperative management of an invasive carcinoma arising in association with an intraductal papillary mucinous neoplasm (IPMN), a biologically distinct entity from PanIN-derived pancreatic ductal adenocarcinoma (PDAC), remains largely based on guidelines for PanIN-derived PDAC. To minimize treatment failure and inform disease-specific management, cancer recurrence must be better characterized. Methods: Patients were identified from a prospectively maintained registry between 1996 and 2018. Predictors of recurrence were evaluated by employing Cox regression models to determine risk-adjusted hazard ratios (HR) with 95% confidence intervals (95%CI). The patterns and timing of recurrence were recognized and compared utilizing a log-rank test, respectively. Results: Of the 213 patients included, 92 (43.2%) recurred with a median RFS of 23.7 months (16.7–30.7). The predominant pattern of recurrence included any systemic (65.2%). The median time to local recurrence was longer than systemic (21.6 versus 11.4 months, p = 0.05). Poor differentiation [HR: 3.01, 95%CI (1.06–8.61)] and nodal disease [N1, HR: 2.23, 95%CI (1.12–4.60); and N2, HR: 5.67 95%CI (2.93–10.99)] emerged as independent predictors of systemic recurrence. For local-specific recurrences, poor differentiation [HR: 3.73, 95%CI (1.04–13.45)] and an R1 margin [high-grade dysplasia or invasive carcinoma; HR: 2.66, 95%CI (1.14–6.21)] emerged as independent predictors. Conclusions: The predominant pattern of recurrence after resection of invasive carcinomas arising in association with IPMNs is systemic, and occurs earlier than local recurrence. Poor differentiation and nodal disease are associated with systemic recurrence while poor differentiation and an R1 margin are associated with local recurrence. Future studies should investigate the role of systemic (chemotherapy) versus local (radiation) therapies and surveillance strategies in a personalized manner. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

One of the newest diagnostic methods and treatment of cancer is to design new drugs. It is now possible to design a drug with desired properties in theory and evaluate its therapeutic effects through bioinformatics tools. Among the studied drugs, those based on cytokine genes, which increase the body's immunity against cancer, are of great interest. Cytokines are small proteins that play an essential role in cell signaling and can affect the function and behavior of surrounding cells. CCL21 chemokine is one of the cytokines that possess antitumor properties has the potential for chemoattraction of T lymphocytes and dendritic cells. Interleukin 1 beta (IL1ß) is a cytokine involving different cellular activities such as the activation of neutrophils, B-Cells, and T-Cells. In the present study, we designed a drug-based cytokine gene to activate T cells and B cells by inserting defined CCL21 epitope and IL1ß peptide sequences into a protein construct. Molecular dynamics simulation was performed in Linux space using Gromex software. Results of RMSD, RMSF, and the radius of gyration obtained from the simulation showed the stability of both proteins, which indicated that there are no significant conformational differences between the commercial CCL21 and recombinant form. The interaction of synthetic construct and human CCL21 with the CCR7 receptor was also investigated by HADDOCK software. Obtained results showed no differences between these proteins, and recombinant protein has the same structural and conformational characteristics as human commercial CCL21. [ABSTRACT FROM AUTHOR]

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<0.001), protein (OR: 2.04; 95% CI: 1.17-3.55; P-trend=0.011), cholesterol (OR: 2.22; 95% CI: 1.28-3.85; P-trend=0.005), and percent of calories from protein (OR: 3.09; 95% CI: 1.69-5.61; P-trend<1.001) showed a positive significant association with SC. Moreover, a significantly negative association was found between the percent of calories obtained from carbohydrates and SC (OR: 0. 57; 95% CI: 0.33-0.98; P-trend=0.015). Conclusion: The findings in this study showed that macronutrient intakes might be associated with the etiology of SC in Iran. [ABSTRACT FROM AUTHOR]

Background: 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.Methods: 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.Results: 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).Conclusions: 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. [ABSTRACT FROM AUTHOR]

Background: 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.Methods: 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.Results: 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 < 0.001) when evaluated among patients included in the training cohort. On validation, the rFI demonstrated good model discrimination (AUROC = 0.68) and was accurately able to risk-stratify patients within the validation cohort at risk for developing a postoperative complication, prolonged length-of-stay, and postoperative mortality (all p < 0.05).Conclusion: Frailty, as measured by the rFI, was predictive of increased risk of morbidity and mortality following liver surgery and can be used to guide patient decision-making. [ABSTRACT FROM AUTHOR]

Introduction: 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.Materials and Methods: 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.Results: 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 <10 4.9 %; MELD ≥10, 10 %; P = 0.001) and ALBI (grade 1, 4.0 %; grade 2, 7.2 %; grade 3, 10.0 %; P = 0.001) were associated with PHLF occurrence, while only ALBI predicted PHLF severity (P = 0.008). Moreover, ALBI was associated with BL (grade 1, 7.1 %; grade 2, 11.5 %; grade 3, 14.0 %; P < 0.001), whereas MELD was not (MELD <10, 8.4 %; MELD ≥10, 11.2 %; P = 0.13). On multivariable analysis, ALBI grade 2/3 was associated with PHLF (OR 1.57, 95 % CI 1.08-2.27; P = 0.02), PHLF severity (OR 3.06, 95 % CI 1.50-6.23; P = 0.003), and the development of a BL (OR 1.35, 95 % CI 1.02-1.80; P = 0.04).Conclusion: The ALBI score was associated with short-term post-operative outcomes following hepatic resection and represents a useful pre-operative risk-assessment tool to identify patients at risk for adverse post-operative outcomes. [ABSTRACT FROM AUTHOR]

Introduction: There is limited evidence characterizing the impact of glycemic alterations on short-term outcomes among patients undergoing resection of colorectal liver metastases (CRLM).Methods: Hyperglycemia was defined as a glucose value >125 mg/dl according to WHO definition. The impact of early postoperative hyperglycemia on short-term postoperative outcomes was assessed.Results: 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. glucose >125 mg/dl, 5 days, P < 0.001).Conclusions: 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. [ABSTRACT FROM AUTHOR]

Background: The optimal tumor-free margin width remains controversial and may be inappropriate to investigate without considering differences in the underlying tumor biology. Methods: R1 resection was defined as margin clearance less than 1 mm. R0 resection was further divided into 3 groups: 1-4, 5-9, and ≥10 mm. The impact of margin width on overall survival (OS) relative to KRAS status [wild type (wt KRAS) vs. mutated (mut KRAS)] was assessed. Results: A total of 411 patients met inclusion criteria. Median patient age was 58 years (interquartile range, 49.7-66.7); most patients were male ( n = 250; 60.8 %). With a median follow-up of 28.3 months, median and 5-year OS were 69.8 months and 55.1 %. Among patients with wt KRAS tumors, although margin clearance of 1-4 mm or more was associated with improved OS compared to R1 (all P < 0.05), no difference in OS was observed when comparing margin clearance of 1-4 mm to the 5-9 mm and the ≥10 mm groups (all P > 0.05). In contrast, among patients with mut KRAS tumors, all three groups of margin clearance (1-4, 5-9, and ≥10 mm) fared no better in terms of 5-year survival compared to R1 resection (all P > 0.05). Conclusions: While a 1-4 mm margin clearance in patients with wt KRAS tumors was associated with improved survival, wider resection width did not confer an additional survival benefit. In contrast, margin status-including a 1 cm margin-did not improve survival among patients with mut KRAS tumors. [ABSTRACT FROM AUTHOR]

Introduction: The interplay of tumor biology and surgical margin status after resection for colorectal liver metastasis (CRLM) remains controversial. Consequently, we sought to determine the impact of surgical margin status on overall survival (OS) stratified by KRAS mutational status.Materials and Methods: Four hundred eighty-five patients with known KRAS mutational status were identified. Clinicopathologic and long-term survival data were collected and assessed.Results: On pathology, most patients (n = 380; 78.3 %) had an R0 margin, while 105 (21.7 %) had an R1. Roughly two thirds of tumors were KRAS wild type (wtKRAS) (n = 307, 63.3 %), while 36.7 % (n = 178) had KRAS mutations (mutKRAS). Median and 5-year OS of the entire cohort was 65.8 months and 53.8 %, respectively. An R1 resection was associated with worse 5-year OS compared with R0 (42.4 % vs. 57.1 %; hazard ratio (HR) 1.82, 95 % CI 1.28-2.57; P = 0.001). After controlling for KRAS status, the survival benefit associated with an R0 resection persisted only among patients with wtKRAS tumors (HR 2.16, 95 % CI 1.42-3.30; P < 0.001). In contrast, surgical margin had no impact on OS among patients with mutKRAS tumors (5-year OS R0, 40.7 % vs. R1, 46.7 %; HR 1.34, 95 % CI 0.73-2.48; P = 0.348).Conclusion: The impact of margin status differed by KRAS mutation status. An R0 margin only provided a survival benefit to patients with wtKRAS tumors. Tumor biology and not surgical technique determined prognosis. [ABSTRACT FROM AUTHOR]

Background: Right-sided and left-sided colorectal cancer (CRC) is known to differ in their molecular carcinogenic pathways. We sought to investigate the variable prognostic implication of KRAS mutation after hepatectomy for colorectal liver metastases (CRLM) according to the site of primary CRC. Methods: A total of 426 patients who underwent a curative-intent hepatic resection and whose KRAS status was available were identified. Clinicopathologic characteristics and long-term outcomes were stratified by KRAS status (wild type vs. mutant type) and primary tumor location (right-sided vs. left-sided). Cecum, right and transverse colon were defined as right-sided, whereas left colon and rectum were defined as left-sided. Results: Among patients with a right-sided CRC, 5-year recurrence-free survival (RFS) and overall survival (OS) were not correlated with KRAS status (wild type: 30.8 and 47.2 % vs. mutant type: 38.5 and 49.1 %, respectively) (both P > 0.05). Specifically, mutant-type KRAS was not associated with either RFS or OS on multivariable analysis (hazard ratio [HR] 1.51, 95 % confidence interval [CI] 0.73-3.14, P = 0.23 and HR 1.03, 95 % CI 0.51-2.08, P = 0.95, respectively). In contrast, among patients who underwent resection of CRLM from a left-sided primary CRC, 5-year RFS and OS were worse among patients with mutant-type KRAS (wild type: 23.7 and 57.2 % vs. mutant type: 19.6 and 38.2 %, respectively) (both P < 0.05). On multivariable analysis, mutant-type KRAS remained independently associated with worse RFS and OS among patients with a left-sided primary CRC (HR 1.57, 95 % CI 1.01-2.44, P = 0.04 and HR 1.81, 95 % CI 1.11-2.96, P = 0.02, respectively). Conclusions: KRAS status has a variable prognostic impact after hepatic resection for CRLM depending on the site of the primary CRC. Future studies examining the impact of KRAS status on prognosis after hepatectomy should take into account the primary CRC tumor site. [ABSTRACT FROM AUTHOR]

Background: 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). Methods: 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). Results: 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). Conclusions: 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. [ABSTRACT FROM AUTHOR]

Background: Use of adjuvant chemotherapy (CTx) and chemoradiation therapy (cXRT) for the treatment of gallbladder cancer (GBC) remains varied. We sought to define the utilization and effect of adjuvant therapy for patients with GBC. Methods: Using a multi-institutional national database, 291 patients with GBC who underwent curative-intent resection between 2000 and 2015 were included. Patients with metastasis or an R2 margin were excluded. Results: Median patient age was 66.6 years. Most patients had a T2 (46.2 %) or T3 (38.6 %) lesion, and 37.8 % of patients had lymph node (LN) metastasis. A total of 186 (63.9 %) patients underwent surgery alone, 61 (21.0 %) received CTx, and 44 (15.1 %) patients received cXRT. On multivariable analysis, factors associated with worse overall survival (OS) included T3/T4 stage [hazard ratio (HR) 1.82], LN-metastasis (HR 1.84), lymphovascular invasion (HR 2.02), perineural invasion (HR 1.42), and R1 surgical margin status (HR 2.06); all P < 0.05). In contrast, receipt of CTx/cXRT was associated with improved OS (CTx, HR 0.38; cXRT, HR 0.26; P < 0.001) compared with surgery alone. Similar results were observed for disease-free survival (DFS) (CTx, HR 0.61; cXRT, HR 0.43; P < 0.05). Of note, only patients with high-risk features, such as AJCC T3/T4 stage (HR 0.41), LN metastasis (HR 0.45), and R1 disease (HR 0.21) (all P < 0.05) derived an OS benefit from CTx/cXRT. Conclusions: Adjuvant CTx/cXRT was utilized in 36 % of patients undergoing curative-intent resection for GBC. After adjusted analyses, CTx/cXRT were independently associated with improved long-term outcomes, but the benefit was isolated to only patients with high-risk characteristics. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Scurrula ferruginea (Jack) Danser is one of the mistletoe species belonging to Loranthaceae family, which grows on the branches of many deciduous trees in tropical countries. This study evaluated the antioxidant activities of S. ferruginea extracts. The cytotoxic activity of the selected extracts, which showed potent antioxidant activities, and high phenolic and flavonoid contents, were investigated in human breast cancer cell line (MDA-MB-231) and non-cancer human skin fibroblast cells (HSF-1184). The activities and characteristics varied depending on the different parts of S. ferruginea, solvent polarity, and concentrations of extracts. The stem methanol extract showed the highest amount of both phenolic (273.51 ± 4.84 mg gallic acid/g extract) and flavonoid contents (163.41 ± 4.62 mg catechin/g extract) and strong DPPH• radical scavenging (IC50 = 27.81 μg/mL) and metal chelation activity (IC50 = 80.20 μg/mL). The stem aqueous extract showed the highest ABTS•+ scavenging ability. The stem methanol and aqueous extracts exhibited dose-dependent cytotoxic activity against MDA-MB-231 cells with IC50 of 19.27 and 50.35 μg/mL, respectively. Furthermore, the extracts inhibited the migration and colony formation of MDA-MB-231 cells in a concentration-dependent manner. Morphological observations revealed hallmark properties of apoptosis in treated cells. The methanol extract induced an increase in ROS generation and mitochondrial depolarization in MDA-MB-231 cells, suggesting its potent apoptotic activity. The present study demonstrated that the S. ferruginea methanol extract mediated MDA-MB-231 cell growth inhibition via induction of apoptosis which was confirmed by Western blot analysis. It may be a potential anticancer agent; however, its in vivo anticancer activity needs to be investigated. [ABSTRACT FROM AUTHOR]

Introduction: 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.Methods: 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.Results: 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).Conclusions: 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. [ABSTRACT FROM AUTHOR]

Background: The association of postoperative complications with long-term oncologic outcomes remains unclear. We sought to determine the incidence of complications among patients who underwent surgery for adrenocortical carcinoma (ACC) and define the relationship of morbidity with long-term survival. Methods: Patients who underwent surgery for ACC between 1993 and 2014 were identified from 13 academic institutions participating in the US ACC group study. The incidence and type of the postoperative complications, the factors associated with them as well their association with long-term survival were analyzed. Results: A total of 265 patients with median age of 52 years (IQR 44-63) were identified; at surgery, the majority of patients underwent an open abdominal procedure ( n = 169, 66.8 %). A postoperative complication occurred in 99 patients for a morbidity of 37.4 %; five patients (1.9 %) died in hospital. Factors associated with morbidity included a thoraco-abdominal operative approach (reference: open abdominal; OR 2.85, 95 % CI 1.00-8.18), and a hormonally functional tumor (OR 3.56, 95 % CI 1.65-7.69) (all P < 0.05). Presence of any complication was associated with a worse long-term outcome (median survival: no complication, 58.9 months vs. any complication, 25.1 months; P = 0.009). In multivariate analysis, after adjusting for patient- and disease-related factors postoperative infectious complications independently predicted shorter overall survival (hazard ratio (HR) 5.56, 95 % CI 2.24-13.80; P < 0.001). Conclusion: Postoperative complications were independently associated with decreased long-term survival after resection for ACC. The prevention of complications may be important from an oncologic perspective. [ABSTRACT FROM AUTHOR]

Background: Adrenocortical carcinoma (ACC) is a rare malignancy. The aim of this study was to determine the incidence and patterns of recurrence after curative-intent surgery for ACC. Methods: Patients who underwent curative-intent resection for ACC between 1993 and 2014 were identified from 13 academic institutions participating in the United States ACC study group. Patients with metastasis or an R2 margin were excluded. Patterns and rates of recurrence were determined and classified as locoregional and distant recurrence. Results: A total of 180 patients with a median age of 52 years (interquartile range 43-61) were identified. Most patients underwent open surgery ( n = 111, 64.5 %) and had an R0 resection margin ( n = 117, 75.0 %). At last follow-up, 116 patients (64.4 %) had experienced recurrence (locoregional only, n = 41, 36.3 %; distant only, n = 51, 45.1 %; locoregional and distant, n = 21, 18.6 %). Median time to recurrence was 18.8 months. Several factors were associated with locoregional recurrence, including left-sided ACC location (odds ratio [OR] 2.71, 95 % confidence interval [CI] 1.06-6.89) and T3/T4 disease (reference T1/T2, OR 3.04, 95 % CI 1.19-7.80) (both p < 0.05). Distant recurrence was associated with larger tumor size (OR 1.11, 95 % CI 1.01-1.24) and T3/T4 disease (reference T1/T2, OR 5.23, 95 % CI 1.70-16.10) (both p < 0.05). Patients with combined locoregional and distant recurrence had worse survival (3- and 5-year survival: 39.5, 19.7 %) versus patients with distant-only (3- and 5-year survival 55.1, 43.3 %) or locoregional-only recurrence (3- and 5-year survival 81.4, 64.1 %) ( p = 0.01). Conclusions: Nearly two-thirds of patients experienced disease recurrence after resection of ACC. Although a subset of patients experienced recurrence with locoregional disease only, many patients experienced recurrence with distant disease as a component of recurrence and had a poor prognosis. [ABSTRACT FROM AUTHOR]

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, IC 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. [ABSTRACT FROM AUTHOR]

Background: While sarcopenia is typically defined using total psoas area (TPA), characterizing sarcopenia using only a single axial cross-sectional image may be inadequate. We sought to evaluate total psoas volume (TPV) as a new tool to define sarcopenia and compare patient outcomes relative to TPA and TPV. Method: Sarcopenia was assessed in 763 patients who underwent pancreatectomy for pancreatic adenocarcinoma between 1996 and 2014. It was defined as the TPA and TPV in the lowest sex-specific quartile. The impact of sarcopenia defined by TPA and TPV on overall morbidity and mortality was assessed using multivariable analysis. Result: Median TPA and TPV were both lower in women versus men (both P < 0.001). TPA identified 192 (25.1 %) patients as sarcopenic, while TPV identified 152 patients (19.9 %). Three hundred sixty-nine (48.4 %) patients experienced a postoperative complication. While TPA-sarcopenia was not associated with higher risk of postoperative complications (OR 1.06; P = 0.72), sarcopenia defined by TPV was associated with morbidity (OR 1.79; P = 0.002). On multivariable analysis, TPV-sarcopenia remained independently associated with an increased risk of postoperative complications (OR 1.69; P = 0.006), as well as long-term survival (HR 1.46; P = 0.006). Conclusion: The use of TPV to define sarcopenia was associated with both short- and long-term outcomes following resection of pancreatic cancer. Assessment of the entire volume of the psoas muscle (TPV) may be a better means to define sarcopenia rather than a single axial image. [ABSTRACT FROM AUTHOR]

Background: We sought to evaluate trends in selection of high volume (HV) hospitals for pancreatic surgery, as well as examine trends in preoperative complications, mortality, and failure to rescue (FTR). Method: Patients who underwent pancreatic resection between 2000 and 2011 were identified from the Nationwide Inpatient Sample (NIS). Preoperative morbidity, mortality, and FTR were examined over time. Hospital volume was stratified into tertiles based on the number of pancreatic resections per year for each time period. Logistic regression models were used to assess the effect of hospital volume on risk of complication, postoperative mortality, and FTR over time. Result: A total of 35,986 patients were identified. Median hospital volume increased from 13 in 2000-2003 to 55 procedures/year in 2008-2011 ( P < 0.001). Morbidity remained relatively the same over time at low volume (LV), intermediate volume (IV), and HV hospitals (all P > 0.05). Overall postoperative mortality was 5 %, and it decreased over time across all hospital volumes ( P < 0.05). FTR was more common at LV (12.0 %) and IV (8.5 %) volume hospitals compared with HV hospitals (6.4 %). The improvement in FTR over time was most pronounced at LV and IV hospitals versus HV hospitals ( P = 0.001). Conclusion: Median hospital volume for pancreatic surgery has increased over the past decade. While the morbidity remained relatively stable over time, mortality improved especially in LV and IV hospitals. This improvement in mortality seems to be related to a decreased FTR. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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). Results: 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 < 0.001). When assessed using categorical values, LNR (C index 0.620) and LODDS (C index = 0.630) showed a better prognostic performance than the AJCC 7th edition staging system (C index = 0.607). When assessed using continuous values, the LODDS staging system (C index = 0.626) slightly outperformed LNR (C index = 0.621). There was heterogeneity of outcomes among patients with no LN involved (LNR = 0) or all LN involved (LNR = 1), indicating that LODDS may better characterize and stratify outcomes among these groups. Conclusions: LODDS and LNR showed better prognostic performance than the AJCC 7th edition staging system. When assessed as categorical and continuous variables, LODDS outperformed LNR, especially among those patients with either very low or high LNR. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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 <10 g/dL; postoperative: Hb <8 g/dL). Results: Four hundred forty-two patients underwent either a pancreas (58.1 %) or liver (41.9 %) resection. Most tumors were pancreatic in origin (41.8 %), while a subset were primary (23.1 %) or secondary (18.8 %) liver tumors. One hundred seventy-five (39.6 %) patients received ≥1 PRBC transfusion either intraoperatively (16.7 %), postoperatively (12.7 %), or both (10.2 %). There was a higher incidence of PRBC transfusion among patients undergoing a pancreas resection, those with higher comorbidities, and those with lower preoperative Hb levels. Perioperative morbidity was higher among patients receiving either 1-2 units (OR 3.14) or 3 or more units of PRBC (OR 8.54). Median OS was 31.9 months. Receipt of a blood transfusion was associated with a worse OS (1-2 units: HR 1.76; 3 + units: HR 2.50; both P < 0.05), and RFS (3 + units: HR 2.91; P = 0.02). Utilization of a restrictive transfusion strategy did not impact perioperative morbidity or long-term RFS or OS. Conclusions: Adoption of a more restrictive transfusion strategy in patients undergoing resection for cancer may preserve a limited resource, reduce costs, as well as avoid exposing oncology patients to the unnecessary risks associated with a transfusion. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia is a surrogate marker of patient frailty that estimates the physiologic reserve of an individual patient. We sought to investigate the impact of sarcopenia on short- and long-term outcomes in patients having undergone surgical intervention for primary hepatic malignancies. Methods: Ninety-six patients who underwent hepatic resection or liver transplantation for HCC or ICC at the John Hopkins Hospital between 2000 and 2013 met inclusion criteria. Sarcopenia was assessed by the measurement of total psoas major volume (TPV) and total psoas area (TPA). The impact of sarcopenia on perioperative complications and survival was assessed. Results: Mean age was 61.9 years and most patients were men (61.4 %). Mean adjusted TPV was lower in women (23.3 cm/m) versus men (34.9 cm/m) ( P < 0.01); 47 patients (48.9 %) had sarcopenia. The incidence of a postoperative complication was 40.4 % among patients with sarcopenia versus 18.4 % among patients who did not have sarcopenia ( P = 0.01). Of note, all Clavien grade ≥3 complications ( n = 11, 23.4 %) occurred in the sarcopenic group. On multivariable analysis, the presence of sarcopenia was an independent predictive factor of postoperative complications (OR = 3.06). Sarcopenia was not associated with long-term survival (HR = 1.23; P = 0.51). Conclusions: Sarcopenia, as assessed by TPV, was an independent factor predictive of postoperative complications following surgical intervention for primary hepatic malignancies. [ABSTRACT FROM AUTHOR]

The role of lymph node dissection (LND) in the treatment of patients with hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC) remains controversial. We sought to systematically review all available evidence to determine the role of LND in patients with HCC and ICC. Studies that reported on LND, lymph node metastasis (LNM), and short- and long-term outcomes for patients with HCC or ICC survival were identified from PubMed, Cochrane, Embase, Scopus, and Web of Science databases. Data were extracted, synthesized, and analyzed using standard techniques. A total of 603 and 434 references were identified for HCC and ICC, respectively. Among HCC patients, the overall prevalence of LND was 51.6 % (95 % confidence interval (CI) 19.7-83.5) with an associated LNM incidence of 44.5 % (95 % CI 27.4-61.7). LNM was associated with a 3- and 5-year survival of 27.5 and 20.8 %, respectively. Among ICC patients, most patients 78.5 % (95 % CI 76.2-80.7) underwent LND; 45.2 % (95 % CI 39.2-51.2) had LNM. Three and 5-year survival among ICC patients with LNM was 0.2 % (95 % CI 0-0.7) and 0 %, respectively. While there are insufficient data to recommend a routine LND in all patients with HCC or ICC, the potential prognostic value of LND suggests that LND should at least be considered at the time of surgery. [ABSTRACT FROM AUTHOR]

Background: Surgeon experience has been shown to influence outcomes for many types of cancer. The factors that patients consider when selecting a hospital or surgeon for cancer treatment remain poorly defined. Methods: All patients with a cancer diagnosis seeking treatment at a surgical clinic at Johns Hopkins Hospital were asked to participate. A survey utilizing a best-worst scaling methodology was constructed to elicit the importance of various factors when selecting a cancer surgeon. Attributes were grouped into four categories: surgeon reputation, surgeon qualifications, hospital-related factors, and nonclinical factors. Results: Two hundred fourteen patients with a cancer diagnosis participated in the study (82.0 % response rate). Patients placed the highest value on physician qualifications and hospital-related factors. Specifically, surgeon case-specific experience (coefficient 2.56, SE 0.06) and the receipt of specialized training by the surgeon (coefficient 2.32, SE 0.06) ranked highest (both P < 0.001). Among hospital-related factors, hospital case-specific volume (coefficient 1.32, SE 0.06; P < 0.001) was most important. The lowest rated factors were parking availability (coefficient −2.81, SE 0.06) and home-to-clinic distance (coefficient −2.12, SE 0.06) (both P < 0.001). The majority of patients reported their ideal surgeon to have at least 6 years of experience ( n = 143, 68.1 %) and to have performed their specific procedure at least 50 times ( n = 156, 75.3 %). Conclusions: Patients consider several factors when choosing a cancer surgeon. Surgeon qualifications and hospital-related factors appear to be most influential in their decision. Easier and more widespread dissemination of surgeon and hospital cancer data such as case volume may be useful for patients. [ABSTRACT FROM AUTHOR]