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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.

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

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

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.

According to the United States census bureau 20% of Americans will be older than 65 years in 2030 and half of them will need an operation - equating to about 36 million older surgical patients. Older adults are prone to complications during gastrointestinal cancer treatment and therefore may need to undergo special pretreatment assessments that incorporate frailty and sarcopenia assessments. A focused, structured literature review on PubMed and Google Scholar was performed to identify primary research articles, review articles, as well as practice guidelines on frailty and sarcopenia among patients undergoing gastrointestinal surgery. The initial search identified 450 articles; after eliminating duplicates, reports that did not include surgical patients, case series, as well as case reports, 42 publications on the impact of frailty and/or sarcopenia on outcome of patients undergoing gastrointestinal surgery were included. Frailty is defined as a clinically recognizable state of increased vulnerability to physiologic stressors resulting from aging. Frailty is associated with a decline in physiologic reserve and function across multiple physiologic systems. Sarcopenia is a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength. Unlike cachexia, which is typically associated with weight loss due to chemotherapy or a general malignancy-related cachexia syndrome, sarcopenia relates to muscle mass rather than simply weight. As such, while weight reflects nutritional status, sarcopenia - the loss of muscle mass - is a more accurate and quantitative global marker of frailty. While chronologic age is an important element in assessing a patient's peri-operative risk, physiologic age is a more important determinant of outcomes. Geriatric assessment tools are important components of the pre-operative work-up and can help identify patients who suffer from frailty. Such data are important, as frailty and sarcopenia have repeatedly been demonstrated among the strongest predictors of both short- and long-term outcome following complicated surgical procedures such as esophageal, gastric, colorectal, and hepato-pancreatico-biliary resections.

Although previous reports have focused on factors at the hospital level to explain variations in postoperative outcomes, less is known regarding the effect of provider-specific factors on postoperative outcomes such as failure-to-rescue (FTR) and postoperative mortality. The current study aimed to quantify the relative contributions of surgeon and hospital volume on the volume-outcomes relationship among a cohort of patients undergoing liver resection.Patients undergoing liver surgery for cancer were identified using the Nationwide Inpatient Sample from 2001 and 2009. Multivariable logistic regression analysis was performed to identify factors associated with mortality and FTR. Point estimates were used to calculate the relative effects of hospital and surgeon volume on mortality and FTR.A total of 5,075 patients underwent liver surgery and met inclusion criteria. Median patient age was 62 years (interquartile range, 52-70) and 55.2% of patients were male. Mortality was lowest among patients treated at high-volume hospitals and among patients treated by high-volume surgeons (both P.001). Similar patterns in FTR were noted relative to hospital and surgeon volume (hospital volume: low vs intermediate vs high; 10.3 vs 9.0 vs 5.2%; surgeon volume: low vs intermediate vs high, 11.1 vs 9.1 vs 4.1%; both P.05). On multivariable analysis, compared with high-volume surgeons, lower volume surgeons demonstrated greater odds for mortality (intermediate: odds ratio [OR], 2.27 [95% CI, 1.27-4.06; P = .006]; low, OR, 2.83 [95% CI, 1.52-5.27; P = .001]), and FTR (intermediate: OR, 2.86 [95% CI, 1.53-5.34, P = .001]; low, OR, 3.40 [95% CI, 1.75-6.63; P.001]). While hospital volume accounted for 0.5% of the surgeon volume effect on increased FTR for low-volume surgeons, surgeon volume accounted for nearly all of the hospital volume effect on increased FTR in low-volume hospitals.The risk of complications, mortality, and FTR were less among both high-volume hospitals and high-volume surgeons, but the beneficial effect of volume on outcomes was attributable largely to surgeon volume.

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. 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. 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

BackgroundInterest in laparoscopic liver resection (LLR) has grown since the International ‘Louisville Statement’ regarding laparoscopic liver surgery was published in 2009. However, limited population based data on LLR utilization patterns and outcomes are available.MethodsLLR data from the Nationwide Inpatient Sample (NIS, 2000–2012) and the National Surgical Quality Improvement Project (NSQIP, 2005–2012) were compared before and after the Louisville Statement in 2009.ResultsIn total, 1131 and 642 LLR were identified from NIS and NSQIP, respectively. Three quarters of patients underwent LLR for a malignant indication (NIS primary malignancy, 29.6% versus metastasis, 45.1%; NSQIP primary malignancy, 35.5% versus metastasis, 46.1%). The annual volume of LLR increased from 2000–2008 versus 2009–2012 (NIS: 63 versus 168, P 0.050). After 2009, LLR was associated with a shorter length of stay (LOS) (NIS: 5 versus 6 days, P = 0.007).ConclusionSince the Louisville Statement in 2009, utilization of LLR has increased. LLR is associated with a modest decrease in LOS and appears to be safe with mortality and morbidity similar to open surgery.

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).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.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).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.

Epidural analgesia (EA) has been used to manage peri- and postoperative pain among patients undergoing major abdominal surgery over the last several decades.1,2 More recently, there has been increasing interest in locoregional analgesia as EA has become an important component of enhanced recovery after major surgery (ERAS) programs.3 EA has been proposed as a mechanism to help improve the perioperative surgical and anesthetic management of patients undergoing surgical procedures in general. Several studies have suggested that EA may not only improve pain control after surgery,4,5 but is also associated with better surgical outcomes compared with conventional analgesia.6–8 Improved outcomes with EA may be related to the ability of locoregional anesthesia to suppress physiologic surgical stress through blockade of nociceptive afferent nerve signaling while preserving motor function.9,10 Furthermore, less narcotic use with EA may also be associated with better bowel function, preservation of pulmonary function, and earlier ambulation after surgery.1,11 Compared with other general surgical procedures, hepatic and pancreatic surgery has historically been associated with poor pain control and more prolonged hospital stays.12,13 The use of EA may therefore be particularly relevant among this patient population. Witzigmann et al14 reported that patients who had better pain relief following hepatopancreatic surgery had less psychological distress, fewer surgical complications, and faster mobilization. In a small randomized clinical trial, Basu et al15 demonstrated the efficacy of EA among patients undergoing liver resection. EA, however, has not been universally adopted for patients undergoing hepatopancreatic surgery. While some studies have reported that EA was associated with decreased postoperative complications, shortened length of hospital stay, and less hospital costs,2,16 other reports have suggested that EA may be associated with increased chance of rapid fluid shifts, more intraoperative hypotension, and perhaps higher blood loss.6,12,17 Moreover, epidural hematoma, a potential complication, may dissuade some surgeons from using EA especially in the setting of a major hepatectomy when postoperative coagulopathy may be a concern.18,19 Currently, data on the utilization of EA among patients undergoing hepatopancreatic surgery are limited. Most previous reports on the use of EA among patients undergoing hepatopancreatic surgery have been limited to single institutions, which may not reflect population-based outcomes.7,12,15,20 As such, we sought to evaluate the relative use of EA among patients undergoing hepatopancreatic surgery in a nationally representative dataset. In particular, the objective of the current study was to define trends in the use of EA for hepatopancreatic procedures, as well as to characterize the perioperative outcomes of patients relative to the use of EA vs non-EA analgesia.

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.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.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).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.

Breast cancer is among the most frequent types of cancer in women worldwide. Current conventional treatment options are accompanied by side effects. Mistletoe is amongst the important herbal medicines traditionally used as complementary remedies. An increasing number of studies have reported anticancer activity of mistletoe extracts on breast cancer cells and animal models. Some recent evidence suggests that cytotoxic activity of mistletoe may be mediated through different mechanisms. These findings provide a good base for clinical trials. Various studies on mistletoe therapy for breast cancer patients revealed similar findings concerning possible benefits on survival time, health-related quality of life (HRQoL), remission rate, and alleviating adverse reactions to conventional therapy. This review provides an overview of the recent findings on preclinical experiments and clinical trials of mistletoe for its cytotoxic and antitumor activity and its effect on HRQoL in breast cancer patients. Moreover, studies investigating molecular and cellular mechanisms underlying antitumor activity of mistletoe are discussed in this paper. The analyzed trials provided evidence that there might be a combination of pharmacological and motivational aspects mediated by the mistletoe extract application which may contribute to the clinical benefit and positive outcome such as improved HRQoL and self-regulation in breast cancer patients.

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.

Background Hepatitis D Virus (HDV) causes the most threatening form of chronic viral hepatitis. To date, there is no overall estimation of HDV prevalence in the Eastern Mediterranean Region Office of WHO (EMRO) countries. Objectives To provide a clear estimation of HDV prevalence in the aforementioned region. Patients and methods In the current systematic review, databases such as PubMed, Embase, Web of sciences and Google scholar were searched Until December 2010. The summary estimate of HDV prevalence in the EMRO region was calculated as an average of the pooled infection prevalence of each country weighted by the ratio of the country's HBV population to the study's sample size in the survey data analysis. Results We included 62 eligible studies. The weighted mean of HDV prevalence in the EMRO region was 14.74% (95% CI: 14.73 - 14.77), 27.8% (95% CI: 27.78 - 27.82), 36.57% (95% CI: 36.55 - 36.59) and 16.44%. (95% CI: 16.42 - 16.46) in asymptomatic HBsAg positive carriers, chronic hepatitis patients, cirrhosis/ hepatocellular carcinoma, and high risk group, respectively. Among the asymptomatic HBsAg positive group, HDV prevalence was increased by years in older patients in Saudi Arabia but its prevalence was decreased in Iran. No specific pattern was seen according to chronological analysis during years among the EMRO countries. Conclusions HDV infection is endemic in the EMRO countries and it is more common among patients with severe forms of hepatitis. Due to the high HDV infection rates in the EMRO countries, we recommend blood screening for HDV infection in this region.

International audience; BACKGROUND: Attempts for early detection of gastric cancer have recently focused on host's genetic susceptibility factors and gene-environment interactions. We have, herein, studied the association of MTHFR C677T single nucleotide polymorphism (SNP) and its interaction with Helicobacter pylori infection, smoking, age and gender on the risk of gastric cancer among an Iranian population. METHODS: Gastric cancer patients (n = 450) and cancer-free controls (n = 780) were studied for serum H. pylori-specific IgG antibodies by ELISA and MTHFR C677T polymorphism (SNP) by PCR-RFLP. Demographic and life style data were collected through patient interviews. Unconditional logistic regression model estimated odds ratio (OR) and the corresponding 95% confidence intervals (CI). RESULTS: The interactions of MTHFR genotype with H. pylori infection (P = 0.03), age (P = 0.049) and gender (P = 0.007) were statistically significant. Accordingly, MTHFR C677T carriers who were also positive for H. pylori infection exhibited 80% (OR = 1.8, 95% CI = 1.0-2.9) significant excess risk of non-cardia gastric cancer. Furthermore, subjects over the age of 50 or female subjects carrying MTHFR C677T SNP showed 40 (OR = 1.4, 95% CI = 1.0-2.0) and 100 (OR = 2.0, 95% CI = 1.2-3.2) percent increased risk of gastric cancer, respectively. CONCLUSION: MTHFR C677T SNP seems to increase the risk of gastric cancer and the effect is significantly inflated by interactions with H. pylori infection, age and gender.