Development and internal validation of a clinical prediction model for serious complications after emergency laparotomy.

PURPOSE: Emergency laparotomy (EL) is a common operation with high risk for postoperative complications, thereby requiring accurate risk stratification to manage vulnerable patients optimally. We developed and internally validated a predictive model of serious complications after EL. METHODS: Data for eleven carefully selected candidate predictors of 30-day postoperative complications (Clavien-Dindo grade > = 3) were extracted from the HELAS cohort of EL patients in 11 centres in Greece and Cyprus. Logistic regression with Least Absolute Shrinkage and Selection Operator (LASSO) was applied for model development. Discrimination and calibration measures were estimated and clinical utility was explored with decision curve analysis (DCA). Reproducibility and heterogeneity were examined with Bootstrap-based internal validation and Internal-External Cross-Validation. The American College of Surgeons National Surgical Quality Improvement Program's (ACS-NSQIP) model was applied to the same cohort to establish a benchmark for the new model. RESULTS: From data on 633 eligible patients (175 complication events), the SErious complications After Laparotomy (SEAL) model was developed with 6 predictors (preoperative albumin, blood urea nitrogen, American Society of Anaesthesiology score, sepsis or septic shock, dependent functional status, and ascites). SEAL had good discriminative ability (optimism-corrected c-statistic: 0.80, 95% confidence interval [CI] 0.79-0.81), calibration (optimism-corrected calibration slope: 1.01, 95% CI 0.99-1.03) and overall fit (scaled Brier score: 25.1%, 95% CI 24.1-26.1%). SEAL compared favourably with ACS-NSQIP in all metrics, including DCA across multiple risk thresholds. CONCLUSION: SEAL is a simple and promising model for individualized risk predictions of serious complications after EL. Future external validations should appraise SEAL's transportability across diverse settings.

Unraveling the Role of Molecular Profiling in Predicting Treatment Response in Stage III Colorectal Cancer Patients: Insights from the IDEA International Study.

BACKGROUND: This study aimed to investigate the molecular profiles of 237 stage III CRC patients from the international IDEA study. It also sought to correlate these profiles with Toll-like and vitamin D receptor polymorphisms, clinicopathological and epidemiological characteristics, and patient outcomes. METHODS: Whole Exome Sequencing and PCR-RFLP on surgical specimens and blood samples, respectively, were performed to identify molecular profiling and the presence of Toll-like and vitamin D polymorphisms. Bioinformatic analysis revealed mutational status. RESULTS: Among the enrolled patients, 63.7% were male, 66.7% had left-sided tumors, and 55.7% received CAPOX as adjuvant chemotherapy. Whole exome sequencing identified 59 mutated genes in 11 different signaling pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) CRC panel. On average, patients had 8 mutated genes (range, 2-21 genes). Mutations in ARAF and MAPK10 emerged as independent prognostic factors for reduced DFS (p = 0.027 and p < 0.001, respectively), while RAC3 and RHOA genes emerged as independent prognostic factors for reduced OS (p = 0.029 and p = 0.006, respectively). Right-sided tumors were also identified as independent prognostic factors for reduced DFS (p = 0.019) and OS (p = 0.043). Additionally, patients with tumors in the transverse colon had mutations in genes related to apoptosis, PIK3-Akt, Wnt, and MAPK signaling pathways. CONCLUSIONS: Molecular characterization of tumor cells can enhance our understanding of the disease course. Mutations may serve as promising prognostic biomarkers, offering improved treatment options. Confirming these findings will require larger patient cohorts and international collaborations to establish correlations between molecular profiling, clinicopathological and epidemiological characteristics and clinical outcomes.

Achieving a Textbook Outcome in Colon Cancer Surgery Is Associated with Improved Long-Term Survival.

BACKGROUND: Colon cancer surgery is a complex clinical pathway and traditional quality metrics may exhibit significant variability between hospitals and healthcare providers. The Textbook Outcome (TO) is a composite quality marker capturing the fraction of patients, in whom all desired short-term outcomes of care are realised. The aim of the present study was to assess the TO in a series of non-metastatic colon cancer patients treated with curative intent, with emphasis on long-term survival. METHODS: Stage I-III colon cancer patients, who underwent curative colectomy following the Complete Mesocolic Excision principles, were retrospectively identified from the institutional database. TO was defined as (i) hospital survival, (ii) radical resection, (iii) no major complications, (iv) no reintervention, (v) no unplanned stoma and (vi) no prolonged hospital stay or readmission. RESULTS: In total, 128 patients (male 61%, female 39%, mean age 70.7 ± 11.4 years) were included in the final analysis. Overall, 60.2% achieved a TO. The highest rates were observed for "hospital survival" and "no unplanned stoma" (96.9% and 97.7%), while the lowest rates were for "no major complications" and "no prolonged hospital stay" (69.5% and 75%). Older age, left-sided resections and pT4 tumours were factors limiting the chances of a TO. The 5-year overall and 5-year cancer-specific survival were significantly better in the TO versus non-TO subgroup (81% vs. 59%, p = 0.009, and 86% vs. 65%, p = 0.02, respectively). CONCLUSIONS: Outcomes in colon cancer surgery may be affected by patient-, doctor- and hospital-related factors. TO represents those patients who achieve the optimal perioperative results, and is furthermore associated with improved long-term cancer survival.

Prospective multicenter external validation of postoperative mortality prediction tools in patients undergoing emergency laparotomy.

BACKGROUND: Accurate preoperative risk assessment in emergency laparotomy (EL) is valuable for informed decision making and rational use of resources. Available risk prediction tools have not been validated adequately across diverse health care settings. Herein, we report a comparative external validation of four widely cited prognostic models. METHODS: A multicenter cohort was prospectively composed of consecutive patients undergoing EL in 11 Greek hospitals from January 2020 to May 2021 using the National Emergency Laparotomy Audit (NELA) inclusion criteria. Thirty-day mortality risk predictions were calculated using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP), NELA, Portsmouth Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity (P-POSSUM), and Predictive Optimal Trees in Emergency Surgery Risk tools. Surgeons' assessment of postoperative mortality using predefined cutoffs was recorded, and a surgeon-adjusted ACS-NSQIP prediction was calculated when the original model's prediction was relatively low. Predictive performances were compared using scaled Brier scores, discrimination and calibration measures and plots, and decision curve analysis. Heterogeneity across hospitals was assessed by random-effects meta-analysis. RESULTS: A total of 631 patients were included, and 30-day mortality was 16.3%. The ACS-NSQIP and its surgeon-adjusted version had the highest scaled Brier scores. All models presented high discriminative ability, with concordance statistics ranging from 0.79 for P-POSSUM to 0.85 for NELA. However, except the surgeon-adjusted ACS-NSQIP (Hosmer-Lemeshow test, p = 0.742), all other models were poorly calibrated ( p < 0.001). Decision curve analysis revealed superior clinical utility of the ACS-NSQIP. Following recalibrations, predictive accuracy improved for all models, but ACS-NSQIP retained the lead. Between-hospital heterogeneity was minimum for the ACS-NSQIP model and maximum for P-POSSUM. CONCLUSION: The ACS-NSQIP tool was most accurate for mortality predictions after EL in a broad external validation cohort, demonstrating utility for facilitating preoperative risk management in the Greek health care system. Subjective surgeon assessments of patient prognosis may optimize ACS-NSQIP predictions. LEVEL OF EVIDENCE: Diagnostic Test/Criteria; Level II.

The Hellenic Emergency Laparotomy Study (HELAS): A Prospective Multicentre Study on the Outcomes of Emergency Laparotomy in Greece.

BACKGROUND: Emergency laparotomy (EL) is accompanied by high post-operative morbidity and mortality which varies significantly between countries and populations. The aim of this study is to report outcomes of emergency laparotomy in Greece and to compare them with the results of the National Emergency Laparotomy Audit (NELA). METHODS: This is a multicentre prospective cohort study undertaken between 01.2019 and 05.2020 including consecutive patients subjected to EL in 11 Greek hospitals. EL was defined according to NELA criteria. Demographics, clinical variables, and post-operative outcomes were prospectively registered in an online database. Multivariable logistic regression analysis was used to identify independent predictors of post-operative mortality. RESULTS: There were 633 patients, 53.9% males, ASA class III/IV 43.6%, older than 65 years 58.6%. The most common operations were small bowel resection (20.5%), peptic ulcer repair (12.0%), adhesiolysis (11.8%) and Hartmann's procedure (11.5%). 30-day post-operative mortality reached 16.3% and serious complications occurred in 10.9%. Factors associated with post-operative mortality were increasing age and ASA class, dependent functional status, ascites, severe sepsis, septic shock, and diabetes. HELAS cohort showed similarities with NELA patients in terms of demographics and preoperative risk. Post-operative utilisation of ICU was significantly lower in the Greek cohort (25.8% vs 56.8%) whereas 30-day post-operative mortality was significantly higher (16.3% vs 8.7%). CONCLUSION: In this study, Greek patients experienced markedly worse mortality after emergency laparotomy compared with their British counterparts. This can be at least partly explained by underutilisation of critical care by surgical patients who are at high risk for death.

Elective surgery for conservatively treated acute uncomplicated diverticulitis: a systematic review of postoperative outcomes.

INTRODUCTION: Elective surgery has been proposed, after at least two episodes of acute diverticulitis, initially treated conservatively, in order to prevent further episodes or chronic complaints. However, prophylactic surgery has been questioned, due to the associated risks of postoperative mortality and morbidity, as well as the risk of recurrent diverticulitis. This systematic review attempts to assess the role of prophylactic left colonic resection, after episodes of uncomplicated acute diverticulitis treated either conservatively with antibiotics and/or other supportive measures. EVIDENCE ACQUISITION: A systematic search was performed using Medline, Embase, Ovid, and Cochrane databases for studies reporting on the treatment of acute uncomplicated diverticulitis (Hinchey I). The main endpoint was treatment failure, defined as persistent/recurrent symptoms or need for readmission and/or reintervention. Secondary endpoints were the immediate postoperative outcomes. EVIDENCE SYNTHESIS: In total, 24 studies with 2855 patients were included in the analysis. Intra- and postoperative complications rate were 5% and 16%, respectively. Anastomotic leak was 1.3% and emergency reoperation was 2.4%. Long-term symptomatic resolve was reported at 91%. Persistent or recurrent symptoms were observed in 5.4% of cases. Meta-analysis showed no significant difference in recurrence rates between surgical and conservative management. CONCLUSIONS: Elective surgery to prevent recurrent diverticulitis is not recommended, irrespective of the number of previous episodes. Generally, elective sigmoidectomy should not be recommended to patients with ongoing atypical lower abdominal symptoms after acute diverticulitis, but should aim primarily at improving quality of life. It should be offered to patients with ongoing inflammation, or diverticular complications.

The Role of Inflammatory Markers in Predicting Resectability of Pancreatic Ductal Adenocarcinoma.

Background: Pancreatic adenocarcinoma is still considered as one of the most aggressive cancers with low percentages of respectability, despite recent advances in diagnosis. Assessment of preoperative inflammatory markers can increase the rates of resectability. Methods: Patients with potentially resectable pancreatic adenoinvesticarcinoma in a single pancreatic unit were included. Ninety-six patient during a one year period were eligible for analysis. Results: CRP, d-dimers, and fibrinogen levels were similar between the two groups. On the contrary, there were statistically significant differences regarding the prognostic nutritional index (PNI) and neutrophil-to-lymphocyte ratio (NLR). Conclusions: inflammatory markers can act as an additional tool in predicting resectability in patients with pancreatic adenocarcinoma.

Cancer-Associated Fibroblasts: The Origin, Biological Characteristics and Role in Cancer-A Glance on Colorectal Cancer.

The therapeutic approaches to cancer remain a considerable target for all scientists around the world. Although new cancer treatments are an everyday phenomenon, cancer still remains one of the leading mortality causes. Colorectal cancer (CRC) remains in this category, although patients with CRC may have better survival compared with other malignancies. Not only the tumor but also its environment, what we call the tumor microenvironment (TME), seem to contribute to cancer progression and resistance to therapy. TME consists of different molecules and cells. Cancer-associated fibroblasts are a major component. They arise from normal fibroblasts and other normal cells through various pathways. Their role seems to contribute to cancer promotion, participating in tumorigenesis, proliferation, growth, invasion, metastasis and resistance to treatment. Different markers, such as a-SMA, FAP, PDGFR-ß, periostin, have been used for the detection of cancer-associated fibroblasts (CAFs). Their detection is important for two main reasons; research has shown that their existence is correlated with prognosis, and they are already under evaluation as a possible target for treatment. However, extensive research is warranted.

Investigation of Microbial Translocation, TLR and VDR Gene Polymorphisms, and Recurrence Risk in Stage III Colorectal Cancer Patients.

Gut microbial dysbiosis and microbial passage into the peripheral blood leads to colorectal cancer (CRC) and disease progression. Toll-like (TLR) and vitamin D (VDR) receptors play important role in the immune modulation and polymorphisms that may increase CRC risk and death rates. The aim of the current study was to demonstrate the prognostic value of microbial DNA fragments in the blood of stage III CRC patients and correlate such microbial detection to TLR/VDR polymorphisms. Peripheral blood was collected from 132 patients for the detection of microbial DNA fragments, and TLR/VDR gene polymorphisms. In the detection of various microbial DNA fragments, TLR and VDR polymorphisms was significantly higher compared to healthy group. Homozygous individuals of either TLR or VDR polymorphisms had significantly higher detection rates of microbial DNA fragments. Mutational and MSI status were significantly correlated with TLR9 and VDR polymorphisms. Significantly shorter disease-free survival was associated with patients with BRAF mutated tumors and ApaI polymorphisms, whereas shorter overall survival was associated with the detection of C. albicans. The detection of B. fragilis, as demonstrated by the multivariate analysis, is an independent poor prognostic factor for shorter disease-free survival. TLR/VDR genetic variants were significantly correlated with the detection of microbial fragments in the blood, and this in turn is significantly associated with tumorigenesis and disease progression.

Ventral Prosthesis Rectopexy for obstructed defaecation syndrome: a systematic review and meta-analysis.

Obstructed Defecation Syndrome (ODS) is a rather complex entity concerning mainly females and causing primarily constipation. Surgical treatment in the form of Ventral Prosthesis Rectopexy (VPR) has been proposed and seems to have the best outcomes. However, the selection criteria of patients to undergo this kind of operation are not clear and the reported outcomes are mainly short-term and data on long-term outcomes is scarce. This study assesses new evidence on the efficacy of VPR for the treatment of ODS, specifically focusing on inclusion criteria for surgery and the long-term outcomes. A search was performed of MEDLINE, EMBASE, Ovid and Cochrane databases on all studies reporting on VPR for ODS from 2000 to March 2020. No language restrictions were made. All studies on VPR were reviewed systematically. The main outcomes were intra-operative complications, conversion, procedure duration, short-term mortality and morbidity, length of stay, faecal incontinence and constipation, quality of life (QoL) score and patient satisfaction. Quality assessment and data extraction were performed independently by three observers. Fourteen studies including 963 patients were eligible for analysis. The immediate postoperative morbidity rate was 8.9%. A significant improvement in constipation symptoms was observed in the 12-month postoperative period for ODS (p < 0.0001). Current evidence shows that VPR offers symptomatic relief to the majority of patients with ODS, improving both constipation-like symptoms and faecal incontinence for at least 1-2 years postoperatively. Some studies report on functional results after longer follow-up, showing sustainable improvement, although in a lesser extent.

Resectable Colorectal Cancer: Current Perceptions on the Correlation of Recurrence Risk, Microbiota and Detection of Genetic Mutations in Liquid Biopsies.

Metastatic colorectal cancer (mCRC) remains a highly lethal malignancy, although considerable progress has resulted from molecular alterations in guiding optimal use of available treatments. CRC recurrence remains a great barrier in the disease management. Hence, the spotlight turns to newly mapped fields concerning recurrence risk factors in patients with resectable CRC with a focus on genetic mutations, microbiota remodeling and liquid biopsies. There is an urgent need for novel biomarkers to address disease recurrence since specific genetic signatures can identify a higher or lower recurrence risk (RR) and, thus, be used both as biomarkers and treatment targets. To a large extent, CRC is mediated by the immune and inflammatory interplay of microbiota, through intestinal dysbiosis. Clarification of these mechanisms will yield new opportunities, leading not only to the appropriate stratification policies, but also to more precise, personalized monitoring and treatment navigation. Under this perspective, early detection of post-operative CRC recurrence is of utmost importance. Ongoing trials, focusing on circulating tumor cells (CTCs) and, even more, circulating tumor DNA (ctDNA), seem to pave the way to a promising, minimally invasive but accurate and life-saving monitoring, not only supporting personalized treatment but favoring patients' quality of life, as well.

Detection of Circulating Tumor Cells and Microbial DNA Fragments in Stage III Colorectal Cancer Patients under Three versus Six Months of Adjuvant Treatment.

Oxaliplatin-fluoropyrimidine combination therapy is the gold standard treatment for patients with stage III colorectal cancer (CRC); however, treatment duration is now under re-evaluation. The aim of the study was the evaluation of the non-inferiority of three over six months treatment with FOLFOX or CAPOX, in stage III CRC patients. Peripheral blood samples from 121 patients were collected, at three time points during treatment and evaluated for circulating tumor cells (CTCs) and microbial DNA detection (16S rRNA, Escherichia coli, Bacteroides fragilis, Candida albicans). Of all patients, 41.3% and 58.7% were treated with FOLFOX and CAPOX, respectively. CTCs were significantly decreased and increased after three and six months of treatment, respectively. CAPOX tends to reduce the CTCs after 3 months, whereas there is a statistically significant increase of CTCs in patients under FOLFOX after 6 months. A significant correlation was demonstrated between microbial DNA detection and both CTCs detection at baseline and CTCs increase between baseline and three months of treatment. To conclude, the current study provides additional evidence of non-inferiority of three over 6 months of treatment, mainly in patients under CAPOX.

Hellenic society of medical oncology (HESMO) guidelines for the management of anal cancer.

Despite considerable improvement in the management of anal cancer, there is a great deal of variation in the outcomes among European countries, and in particular among different hospital centres in Greece and Cyprus. The aim was to elaborate a consensus on the multidisciplinary management of anal cancer, based on European guidelines (European Society of Medical Oncologists-ESMO), considering local special characteristics of our healthcare system. Following discussion and online communication among members of an executive team, a consensus was developed. Guidelines are proposed along with algorithms of diagnosis and treatment. The importance of centralisation, care by a multidisciplinary team (MDT) and adherence to guidelines are emphasised.

Management of the adenocarcinoma of the upper rectum: a reappraisal.

The present review attempts to assess whether upper rectal cancer (URC) should be treated either as colon cancer or as rectal one, namely to be managed with upfront surgery without neo-adjuvant treatment and partial mesorectal excision (PME), or with neo-adjuvant short course radiotherapy (SCRT) or chemoradiotherapy (CRT) as indicated, followed by surgery with total mesorectal excision. Reports from current evidence including studies, reviews and various guidelines are conflicting. Main reasons for inability to reach safe conclusions are (i) the various anatomical definitions of the rectum and its upper part, (ii) the inadequate preoperative local staging,(iii) the heterogeneity of selection criteria for the neo-adjuvant treatment,(iv) the different neo-adjuvant treatment regimens, and(v) the variety in the extent of surgical resection, among the studies. Although not adequately supported, locally advanced URC can be treated with neo-adjuvant CRT provided the lesion is within the radiation field of safety, and a PME if the lower border of the tumour is located above the anterior peritoneal reflection. There is evidence that adjuvant chemotherapy is of benefit in high-risk stage II and stage III lesions.

Immunotherapy in Solid Tumors and Gut Microbiota: The Correlation-A Special Reference to Colorectal Cancer.

Over the last few years, immunotherapy has been considered as a key player in the treatment of solid tumors. Immune checkpoint inhibitors (ICIs) have become the breakthrough treatment, with prolonged responses and improved survival results. ICIs use the immune system to defeat cancer by breaking the axes that allow tumors to escape immune surveillance. Innate and adaptive immunity are involved in mechanisms against tumor growth. The gut microbiome and its role in such mechanisms is a relatively new study field. The presence of a high microbial variation in the gut seems to be remarkably important for the efficacy of immunotherapy, interfering with innate immunity. Metabolic and immunity pathways are related with specific gut microbiota composition. Various studies have explored the composition of gut microbiota in correlation with the effectiveness of immunotherapy. Colorectal cancer (CRC) patients have gained little benefit from immunotherapy until now. Only mismatch repair-deficient/microsatellite-unstable tumors seem to respond positively to immunotherapy. However, gut microbiota could be the key to expanding the use of immunotherapy to a greater range of CRC patients.

Evaluation of the Role of Circulating Tumor Cells and Microsatellite Instability Status in Predicting Outcome of Advanced CRC Patients.

Colorectal cancer (CRC) remains one of the leading causes of cancer-related death due to its high metastatic potential. This study aimed to investigate the detection and heterogeneity of circulating tumor cells (CTCs) and the microsatellite instability (MSI) status in advanced CRC patients prior to any systemic front-line treatment. Peripheral whole blood was obtained from 198 patients. CTCs were detected using double immunofluorescence and a real time-polymerase chain reaction assay; whereas MSI status was evaluated using fragment analysis. Median age of the patients was 66 years, 63.1% were males, 65.2% had a colon/sigmoid tumor location and 90.4% had a good performance status (PS). MSI-High status was detected in 4.9% of the patients; 33.3%, 56.1% and 8.6% patients had at least one detectable CEACAM5+/EpCAM+, CEACAM5+/EpCAM- and CEACAM5-/EpCAM+ CTC, respectively, and 9.1% of the patients had CEACAM5mRNA-positive CTCs. Following multivariate analysis, age, PS and MSI were confirmed as independent prognostic factors for decreased time to progression, whereas age, PS and CTC presence were confirmed as independent prognostic factors for decreased overall survival. In conclusion, our data support the use of CEACAM5 as a dynamic adverse prognostic CTC biomarker in patients with metastatic CRC and MSI-High is considered an unfavorable prognostic factor in metastatic CRC patient tumors.

Neo-adjuvant chemotherapy alone for the locally advanced rectal cancer: a systematic review.

Neo-adjuvant chemoradiation (NA-CRT) is the standard of management for the locally advanced rectal cancer (LARC), achieving very low rates of local recurrence (LR). However, NA-CRT fails to control distant recurrence and improve survival, whilst it is associated with increased postoperative morbidity and increased acute and late toxicity. In recent years, neo-adjuvant chemotherapy (NACTx) appears in the literature as an alternative to NA-CRT in patients with LARC. In the present study, the authors review all current evidence on the specific subject. Following a systematic search of the literature, 25 studies were identified reporting on short- or long-term outcomes of NACTx for LARC. Seventeen studies were prospective or retrospective series, and 8 comparative. Of the comparative studies, one was a randomized control trial (RCT) comparing NACTx to NA-CRT and to the combination of NACTx/NA-CRT, and another a non-randomized study comparing NACTx to NA-CRT. Chemotherapeutic regimens were 5-fluoropyrimidine and oxaliplatin based. In some of them, irinotecan or/and bevacizumab was added. A pooled analysis showed that NACTx is associated with a mean anastomotic leak rate of 6.8%. In the RCT, postoperative morbidity and overall toxicity was significantly less in the NACTx group. Mean T downstaging (ypStage 0-I) was 49.6%, mean N downstaging 69.6% and mean pathologic complete response (pCR) 10.7%. The RCT showed an inferior pCR rate after NACTx than after NA-CRT, but similar rates of T downstaging. Mean LR was 8.6% and mean distant recurrence 17.2%. Satisfactory survival rates are reported by several studies. NACTx seems to be an alternative to NA-CRT for patients with LARC, associated with low anastomotic leak, adequate tumour downstaging, low LR and rather high survival rates. Further data deriving from high-quality studies are necessary to assess safety and efficacy of NACTx as a substitute to NA-CRT, for at least a subset of patients with LARC.

PKM2 Expression as Biomarker for Resistance to Oxaliplatin-Based Chemotherapy in Colorectal Cancer.

The purpose of the current study is to investigate the prognostic significance of M2 isoform of pyruvate kinase (PKM2) mRNA expression loss in patients with operable colon cancer (CC). Two hundred sixty-two specimens from patients with stage-III or high-risk stage-II CC (group-A) treated with adjuvant fluoropyrimidine and oxaliplatin chemotherapy (FOLFOX), 118 specimens from metastatic CC patients (group-B) treated with FOLFOX, and 104 metastatic CC patients (group-C) treated with irinotecan-based chemotherapy were analyzed for PKM2, TS, ERCC1, MYC, and NEDD9 mRNA expression, as well as KRAS exon2 and BRAFV600E mutations. High PKM2 mRNA expression was correlated with left-sided located primaries (p = 0.001, group-A; p = 0.003, group-B; p = 0.001, group-C), high-grade tumors (p = 0.001, group-A; p = 0.017, group-B; p = 0.021, group-C), microsatellite-stable tumors (p < 0.001, group-A), pericolic lymph nodes involvement (p = 0.018, group-A), and cMYC mRNA expression (p = 0.002, group-A; p = 0.008, group-B; p = 0.006, group-C). High PKM2 mRNA expression was correlated with significantly lower disease free survival (DFS) (p = 0.002) and overall survival (OS) (p = 0.001) in the group-A. Similarly, PKM2 mRNA expression was associated with significantly decreased progression free survival (PFS) (p = 0.001) and OS (p = 0.001) in group-B. On the contrary, no significant association for the PKM2 mRNA expression has been observed with either PFS (p = 0.612) or OS (p = 0.517) in group-C. To conclude, the current study provides evidence for the prediction of PKM2 mRNA expression oxaliplatin-based treatment resistance.

The Role of Vitamin D Receptor Gene Polymorphisms in Colorectal Cancer Risk.

Vitamin D deficiency has been associated with increased colorectal cancer (CRC) incidence risk and mortality. Vitamin D mediates its action through the binding of the vitamin D receptor (VDR), and polymorphisms of the VDR might explain these inverse associations. The aim of the study was the investigation of the relevance of rs731236; Thermus aquaticus I (TaqI), rs7975232; Acetobacter pasteurianus sub. pasteurianus I (ApaI), rs2228570; Flavobacterium okeanokoites I (FokI) and rs1544410, Bacillus stearothermophilus I (BsmI) polymorphisms of the VDR gene to colorectal carcinogenesis (CRC) and progression. Peripheral blood was obtained from 397 patients with early operable stage II/III (n = 202) and stage IV (n = 195) CRC. Moreover, samples from 100 healthy donors and 40 patients with adenomatous polyps were also included as control groups. Genotyping in the samples from patients and controls was performed using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP). A significant association was revealed between all four polymorphisms and cancer. Individuals with homozygous mutant (tt, aa, ff or bb) genotypes were more susceptible to the disease (p < 0.001). All of the mutant genotypes detected were also significantly associated with stage IV (p < 0.001), leading to significantly decreased survival (p < 0.001). Moreover, all four polymorphisms were significantly associated with KRAS (Kirsten ras oncogene) mutations and Toll-like receptor (TLR2, TLR4 and TLR9) genetic variants. In multivariate analysis, tt, aa and ff genotypes emerged as independent factors associated with decreased overall survival (OS) (p = 0.001, p < 0.001 and p = 0.001, respectively). The detection of higher frequencies of the VDR polymorphisms in CRC patients highlights the role of these polymorphisms in cancer development and progression.

Consensus statement of the Hellenic and Cypriot Gastric Cancer Study Group on the diagnosis, staging and management of gastric cancer.

Gastric Cancer epidemics have changed over recent decades, declining in incidence, shifting from distal to proximal location, transforming from intestinal to diffuse histology. Novel chemotherapeutic agents combined with modern surgical operations hardly changed overall disease related survival. This may be attributed to a substantial inherent geographical variation of disease genetics, but also to a failure to standardize and implement treatment protocols in clinical practice. To overcome these drawbacks in Greece and Cyprus, a Gastric Cancer Study Group under the auspices of the Hellenic Society of Medical Oncology (HeSMO) and Gastrointestinal Cancer Study Group (GIC-SG) merged their efforts to produce a consensus considering ethnic parameters of healthcare system and the international proposals as well. Utilizing structured meetings of experts, a consensus was reached. To achieve further consensus, statements were subjected to the Delphi methodology by invited multidisciplinary national and international experts. Sentences were considered of high or low consensus if they were voted by ≥ 80%, or < 80%, respectively; those obtaining a low consensus level after both voting rounds were rejected. Forty-five statements were developed and voted by 71 experts. The median rate of abstention per statement was 9.9% (range: 0-53.5%). At the end of the process, one statement was rejected, another revised, and all the remaining achieved a high consensus. Forty-four recommendations covering all aspects of the management of gastric cancer and concise treatment algorithms are proposed by the Hellenic and Cypriot Gastric Cancer Study Group. The importance of centralization, care by a multidisciplinary team, adherence to guidelines, and individualization are emphasized.