Authenticity assessment of ground black pepper by combining headspace gas-chromatography ion mobility spectrometry and machine learning.

Currently, the authentication of ground black pepper is a major concern, creating a need for a rapid, highly sensitive and specific detection tool to prevent the introduction of adulterated batches into the food chain. To this aim, head space gas-chromatography ion mobility spectrometry (HS-GC-IMS), combined with machine learning, is tested in this initial, proof-of-concept study. A broad variety of authentic samples originating from eight countries and three continents were collected and spiked with a range of adulterants, both endogenous sub-products and an assortment of exogenous materials. The method is characterized by no sample preparation and requires 20 min for chromatographic separation and ion mobility data acquisition. After an explorative analysis of the data, those were submitted to two different machine learning algorithms (partial least squared discriminant analysis-PLS-DA and support vector machine-SVM). While the PLS-DA model did not provide fully satisfactory performances, the combination of HS-GC-IMS and SVM successfully classified the samples as authentic, exogenously-adulterated or endogenously-adulterated with an overall accuracy of 90 % and 96 % on withheld test set 1 and withheld test set 2, respectively (at a 95 % confidence level). Some limitations, expected to be mitigated by further research, were encountered in the correct classification of endogenously adulterated ground black pepper. Correct categorization of the ground black pepper samples was not adversely affected by the operator or the time span of data collection (the method development and model challenge were carried out by two operators over 6 months of the study, using ground black pepper harvested between 2015 and 2019). Therefore, HS-GC-IMS, coupled to an intelligent tool, is proposed to: (i) aid in industrial decision-making before utilization of a new batch of ground black pepper in the production chain; (ii) reduce the use of time-consuming conventional analyses and; (iii) increase the number of ground black pepper samples analyzed within an industrial quality control frame.

A geographical origin assessment of Italian hazelnuts: Gas chromatography-ion mobility spectrometry coupled with multivariate statistical analysis and data fusion approach.

Hazelnut is a commodity that has gained interest in the food science community concerning its authenticity. The quality of the Italian hazelnuts is guaranteed by Protected Designation of Origin and Protected Geographical Indication certificates. However, due to their modest availability and the high price, fraudulent producers/suppliers blend, or even substitute, Italian hazelnuts with others from different countries, having a lower price, and often a lower quality. To contrast or prevent these illegal activities, the present work investigated the application of the Gas Chromatography-Ion mobility spectrometry (GC-IMS) technique on the hazelnut chain (fresh, roasted, and paste of hazelnuts). The raw data obtained were handled and elaborated using two different ways, software for statistical analysis, and a programming language. In both cases, Principal Component Analysis and Partial Least Squares-Discriminant Analysis models were exploited, to study how the Volatile Organic Profiles of Italian, Turkish, Georgian, and Azerbaijani products differ. A prediction set was extrapolated from the training set, for a preliminary models' evaluation, then an external validation set, containing blended samples, was analysed. Both approaches highlighted an interesting class separation and good model parameters (accuracy, precision, sensitivity, specificity, F1-score). Moreover, a data fusion approach with a complementary methodology, sensory analysis, was achieved, to estimate the performance enhancement of the statistical models, considering more discriminant variables and integrating at the same time further information correlated to quality aspects. GC-IMS could be a key player as a rapid, direct, cost-effective strategy to face authenticity issues regarding the hazelnut chain.

Acute acalculous cholecystitis and cardiovascular disease, which came first? After two hundred years still the classic chicken and eggs debate: A review of literature.

The existence of a close association between disease of the biliary tract and disease of the heart is known from the mists of time. Acute acalculous cholecystitis (AAC) can be defined as an acute necro inflammatory disease of the gallbladder in the absence of cholelithiasis. AAC is a challenging diagnosis. The atypical clinical onset associated to a paucity and similarity of symptoms and to laboratory data mimicking cardiovascular disease (CVD) often results in under and misdiagnosed cases. Moreover, AAC has commonly a fulminant course compared to calculous cholecystitis and it is often associated with gangrene, perforation and empyema as well as considerable morbidity and mortality (up 50%). Early diagnosis is crucial to a prompt treatment in order to avoid complications and to increase survivability. Even today, although scientific evidence dating two hundred years has shown a close association between AAC and CVD, due to the lack of RCT, there is still a lot of confusion regarding the relationship and consequently the clinical management AAC and CVD. In addition, emergency physicians are not always familiar with transient ECG changes with AAC. The aim of this review was to provide evidence regarding epidemiology, pathophysiology, clinical presentation and treatment of the complex association between AAC and CVD. Our main findings indicate that AAC should be suspected after each general disease leading to hypoperfusion such as cardiovascular diseases or cerebrovascular diseases or major heart or aortic surgery. ECG changes in absence of significant laboratory data for IMA (Acute myocardial infarction) could be related to a misdiagnosed AAC. US - Ultrasonography-plays a key role in the early diagnosis and also in the follow up of AAC. Cholecystostomy and cholecystectomy as unique or sequential represent the two prevailing treatment options for AAC.

Changes in hospital admissions and complications of acute appendicitis during the COVID-19 pandemic: A systematic review and meta-analysis.

Background: Acute appendicitis (AA) is one of the most common emergencies in general surgery worldwide. During the pandemic, a significant decrease in the number of accesses to the emergency department for AA has been recorded in different countries. A systematic review of the current literature sought to determine the impact of Coronavirus Disease 2019 (COVID-19) on hospital admissions and complications of AA. Method: A systematic search was undertaken to identify repeated cross-sectional studies reporting the management of AA during the COVID-19 pandemic (index period) as compared to the previous year, or at the turn of lockdown (reference period). Data were abstracted on article (country of origin) and patients characteristics (adults, children [i.e. non adults, <18-year-old]), or mixed population) within the two given timeframes, including demographics, number of admissions for AA, number of appendectomies, and complicated appendectomies. Results: Of 201 full-text articles assessed for eligibility, 54 studies from 22 world countries were included. In total, 27 (50%) were conducted on adults, 12 (22%) on children, and 15 (28%) on a mixed patients population. The overall rate ratio of admissions for AA between the two periods was 0.94 (95%CI, 0.75-1.17), with significant differences between studies on adults (0.90 [0.74-1.09]), mixed population (0.50 [0.27-0.90]), and children (1.50 [1.01-2.22]). The overall risk ratio of complicated AA was 1.65 (1.32-2.07), ranging from 1.32 in studies on children, to 2.45 in mixed population. Conclusion: The pandemic has altered the rate of admissions for AA and appendectomy, with parallel increased incidence of complicated cases in all age groups.

Association of Delayed Surgery With Oncologic Long-term Outcomes in Patients With Locally Advanced Rectal Cancer Not Responding to Preoperative Chemoradiation.

Importance: Extending the interval between the end of neoadjuvant chemoradiotherapy (CRT) and surgery may enhance tumor response in patients with locally advanced rectal cancer. However, data on the association of delaying surgery with long-term outcome in patients who had a minor or poor response are lacking. Objective: To assess a large series of patients who had minor or no tumor response to CRT and the association of shorter or longer waiting times between CRT and surgery with short- and long-term outcomes. Design, Setting, and Participants: This is a multicenter retrospective cohort study. Data from 1701 consecutive patients with rectal cancer treated in 12 Italian referral centers were analyzed for colorectal surgery between January 2000 and December 2014. Patients with a minor or null tumor response (ypT stage of 2 to 3 or ypN positive) stage greater than 0 to neoadjuvant CRT were selected for the study. The data were analyzed between March and July 2020. Exposures: Patients who had a minor or null tumor response were divided into 2 groups according to the wait time between neoadjuvant therapy end and surgery. Differences in surgical and oncological outcomes between these 2 groups were explored. Main Outcomes and Measures: The primary outcomes were overall and disease-free survival between the 2 groups. Results: Of a total of 1064 patients, 654 (61.5%) were male, and the median (IQR) age was 64 (55-71) years. A total of 579 patients (54.4%) had a shorter wait time (8 weeks or less) 485 patients (45.6%) had a longer wait time (greater than 8 weeks). A longer waiting time before surgery was associated with worse 5- and 10-year overall survival rates (67.6% [95% CI, 63.1%-71.7%] vs 80.3% [95% CI, 76.5%-83.6%] at 5 years; 40.1% [95% CI, 33.5%-46.5%] vs 57.8% [95% CI, 52.1%-63.0%] at 10 years; P < .001). Also, delayed surgery was associated with worse 5- and 10-year disease-free survival (59.6% [95% CI, 54.9%-63.9%] vs 72.0% [95% CI, 67.9%-75.7%] at 5 years; 36.2% [95% CI, 29.9%-42.4%] vs 53.9% [95% CI, 48.5%-59.1%] at 10 years; P < .001). At multivariate analysis, a longer waiting time was associated with an augmented risk of death (hazard ratio, 1.84; 95% CI, 1.50-2.26; P < .001) and death/recurrence (hazard ratio, 1.69; 95% CI, 1.39-2.04; P < .001). Conclusions and Relevance: In this cohort study, a longer interval before surgery after completing neoadjuvant CRT was associated with worse overall and disease-free survival in tumors with a poor pathological response to preoperative CRT. Based on these findings, patients who do not respond well to CRT should be identified early after the end of CRT and undergo surgery without delay.

Evolution of Surgical Management of Hemorrhoidal Disease: An Historical Overview.

Hemorrhoidal disease (HD) is the symptomatic enlargement and/or distal displacement of the normal hemorrhoidal cushions and is one of the most frequent diseases in colorectal surgery. Several surgical or office-based therapies are currently available, with the aim of being a more tailored approach. This article aimed to elucidate the historical evolution of surgical therapy for HD from ancient times, highlighting the crucial steps, controversies, and pioneers in the field. In contrast with the previous literature on the topic that is often updated to the 1990s, with the introduction of stapled hemorrhoidopexy and transanal hemorrhoidal dearterialization, this article describes all new surgical and office-based treatments introduced in the first 20 years of the 2000s.

What paradigm shifts occurred in the management of acute diverticulitis during the COVID-19 pandemic? A scoping review.

BACKGROUND: Acute colonic diverticulitis (ACD) is common in Western countries, with its prevalence increasing throughout the world. As a result of the coronavirus disease 2019 (COVID-19), elective surgery and in-patients' visits have been cancelled or postponed worldwide. AIM: To systematically explore the impact of the pandemic in the management of ACD. METHODS: MEDLINE, Embase, Scopus, MedxRiv, and the Cochrane Library databases were searched to 22 December 2020. Studies which reported on the management of patients with ACD during the COVID-19 pandemic were eligible. For cross sectional studies, outcomes of interest included the number of hospital admission for ACD, as well as key features of disease severity (complicated or not) across two time periods (pre- and during lockdown). RESULTS: A total of 69 papers were inspected, and 21 were eligible for inclusion. Ten papers were cross sectional studies from seven world countries; six were case reports; three were qualitative studies, and two review articles. A 56% overall decrease in admissions for ACD was observed during lockdown, peaking 67% in the largest series. A 4%-8% decrease in the rate of uncomplicated diverticulitis was also noted during the lockdown phase. An initial non-operative management was recommended for complicated diverticulitis, and encouraged to an out-of-hospital regimen. Despite initial concerns on the use of laparoscopy for Hinchey 3 and 4 patients to avoid aerosolized contamination, societal bodies have progressively mitigated their initial recommendations as actual risks are yet to be ascertained. CONCLUSION: During the COVID-19 pandemic, fewer patients presented and were diagnosed with ACD. Such decline may have likely affected the spectrum of uncomplicated disease. Established outpatient management and follow up for selected cases may unburden healthcare resources in time of crisis.

Endoscopic Pilonidal Sinus Treatment: A Tertiary Care Academic Center Experience.

Background: Pilonidal disease (PD) represents one of the most common proctological diseases in young adults. Although several approaches to treating PD have been described, there is still a lack of agreement on which is the best. The aim of this study was to evaluate the long-term efficacy of endoscopic pilonidal sinus treatment (EPSiT) at a tertiary care academic center. Methods: Between June 2017 and January 2021, a total of 32 patients [12 women (37.5%) and 20 men (62.5%)] with a mean age of 29.22 ± 12.98 years were treated with EPSiT. Pre- and post-operative symptoms were assessed with a score of 0-5. Success was defined as the absence of any subjective symptoms, as well as by complete post-operative wound healing. Results: Most of the patients had a midline external opening (17/32; 53.1%), with a mean number of external openings of 2.41 (1-4) ± 1.04. The median post-operative pain score was 0, and the mean follow-up period was 22 (4-42) ± 11.49 months. The time to wound healing was reduced in patients with one opening (28.14 ± 4.06 days) compared to patients with two or more openings (33.64 ± 7.3 days) (p = 0.067). The mean operative time was longer in patients who subsequently had a recurrence (41.75 ± 6.24 vs. 34.18 ± 6.24 min; p = 0.031). The overall success rate was 87.5% (28/32), and the mean time to recurrence was 3.25 (2-5) ± 1.26 months. Conclusions: EPSiT represents a viable option for the treatment of PD. More evidence and a longer follow-up period are needed to validate the results.

Anatomo-functional outcomes of the laparoscopic Frykman-Goldberg procedure for rectal prolapse in a tertiary referral centre.

Rectal prolapse is a common disorder that represents a burden for patients due to the associated symptoms that may include both incontinence and constipation. Currently, a huge variation in techniques exist. The aim of this study was to evaluate the anatomo-functional results of the laparoscopic Frykman-Goldberg procedure (LFGP) for the treatment of both internal (IRP) and complete rectal prolapse (CRP). Between July 2004 and October 2019, 45 patients with IRP and CRP underwent a LFGP. The Cleveland Clinic Constipation Score (CCCS), Obstructed Defecation Syndrome Score (ODSS) and Vaizey Score (VS) were assessed preoperatively, 3 months before the procedure, 12 months after the procedures and at the final follow-up visit. The patients' mean age was 51.4 ± 17.9 (15-93) years, and the mean follow-up was 9.24 ± 4.57 (1.6-16.3) years. The VS, CCCS and ODSS significantly improved (p = 0.008; p < 0.001; p < 0.001) from median preoperative values of 3, 20 and 18 to 2, 6 and 5, respectively. Furthermore, the improvements in scores during follow-up remained constant and significant over time when considering the two groups separately (time effect for ODSS p < 0.001, for VS p = 0.026, for CCCS p < 0.001) and when the patients were divided by age (< 40, 41-60 and > 60; p < 0.001). The overall complication rate was 8.9% (4/45), and no intraoperative complications or anastomotic leakage occurred. Conversion to the open approach was not necessary in any case. The overall success rate was 97.7%, and only one recurrence in the IRP group occurred after 14 months. LRGP can be considered a safe, effective and long-lasting procedure in young patients with IRP or CRP, a history of ODS and a redundant sigmoid colon.

Therapeutic Targets and Tumor Microenvironment in Colorectal Cancer.

Colorectal cancer (CRC) is a genetically, anatomically, and transcriptionally heterogeneous disease. The prognosis for a CRC patient depends on the stage of the tumor at diagnosis and widely differs accordingly. The tumor microenvironment (TME) in CRC is an important factor affecting targeted cancer therapy. The TME has a dynamic composition including various cell types, such as cancer-associated fibroblasts, tumor-associated macrophages, regulatory T cells, and myeloid-derived suppressor cells, as well as extracellular factors that surround cancer cells and have functional and structural roles under physiological and pathological conditions. Moreover, the TME can limit the efficacy of therapeutic agents through high interstitial pressure, fibrosis, and the degradation of the therapeutic agents by enzymatic activity. For this reason, the TME is a fertile ground for the discovery of new drugs. The aim of this narrative review is to present current knowledge and future perspectives regarding the TME composition based on strategies for patients with CRC.

Excisional Haemorrhoidectomy: Where Are We?

Haemorrhoidal disease (HD) is defined as the symptomatic enlargement and/or distal displacement of anal cushions and is one of the most frequent and ancient anorectal conditions. Bleeding, during or after defecation, is the most common symptom. The color of the blood is typically bright red covering the outer surface of the stools. The severity of HD is based on the degree of the prolapse. There are several excisional surgery treatments. In this review, we describe the most common techniques such as Milligan and Morgan, Parks, Ferguson and Whitehead technique. Despite significant improvements in conservative treatments, excisional haemorrhoidectomy techniques are the most effective treatment for III- and IV degree.

Mesenchymal Stromal Cell Therapy in the Management of Perianal Fistulas in Crohn's Disease: An Up-To-Date Review.

Crohn's Disease (CD) is a chronic inflammatory disorder that potentially involves the entire gastrointestinal tract. Perianal fistulizing CD (pCD) is a serious and frequent complication associated with significant morbidities and a heavy negative impact on quality of life. The aim of CD treatment is to induce and maintain disease remission and to promote mucosal repair. Unfortunately, even the best therapeutic regimens in pCD do not have long-term efficacy and cause a significant number of side effects. Therefore, it is mandatory to study new therapeutical options such as the use of mesenchymal stromal cells (MSCs). These cells promote tissue repair via the induction of immunomodulation. The present review aims to analyze the existing updated scientific literature on MSCs adoption in the treatment of pCD to evaluate its efficacy and safety and to compare the use of bone marrow and adipose tissue derived MSCs, type of administration, and dose required for recovery.

Mast Cells, microRNAs and Others: The Role of Translational Research on Colorectal Cancer in the Forthcoming Era of Precision Medicine.

Colorectal cancer (CRC) is a heterogeneous disease, molecularly and anatomically, that develops in a multi-step process requiring the accumulation of several genetic or epigenetic mutations that lead to the gradual transformation of normal mucosa into cancer. In fact, tumorigenesis is extremely complex, with many immunologic and non-immunologic factors present in the tumor microenvironment that can influence tumorigenesis. In the last few years, a role for mast cells (MCs), microRNAs (miRNAs), Kirsten rat sarcoma (KRAS) and v-raf murine sarcoma viral oncogene homologue B (BRAF) in cancer development and progression has been suggested, and numerous efforts have been made to thoroughly assess their correlation with CRC to improve patient survival and quality of life. The identification of easily measurable, non-invasive and cost-effective biomarkers, the so-called "ideal biomarkers", for CRC screening and treatment remains a high priority. The aim of this review is to discuss the emerging role of mast cells (MCs), microRNAs (miRNAs), KRAS and BRAF as diagnostic and prognostic biomarkers for CRC, evaluating their influence as potential therapy targets in the forthcoming era of precision medicine.

Practical approach to develop a multi-group screening method for detection of mycotoxins, pesticides and veterinary drugs in food.

A multi-group screening method to detect residues of veterinary drugs in meat and environmental contaminants in wheat flour has been developed using liquid chromatography coupled to quadrupole-Orbitrap high-resolution mass spectrometry (LC-HRMS). The procedure was tested for over 300 representative compounds (173 veterinary drugs, 122 pesticides and 9 mycotoxins) analysing in parallel negative and positive (spiked) samples according to European validation rules. The Screening Target Concentrations (STCs) were chosen conservatively with respect to the method purposes. Interpretation of results was based on retention time, mass accuracy of precursor and MS2 spectral library. Evaluating the percentage of false negative results, 280 out of the 304 analytes were detectable at the STCs (false compliant rate ≤ 5%). In wheat flours, incurred levels of mycotoxins, deoxynivalenol and 3-acetyldeoxynivalenol, higher than STCs, were frequently found, whereas in meat, the most detected veterinary drugs were antibiotics generally at negligible concentrations (<10 µg kg-1 ). Finally, seven test materials from proficiency test schemes were successfully tested.

Total thyroidectomy vs completion thyroidectomy for thyroid nodules with indeterminate cytology/follicular proliferation: a single-centre experience.

BACKGROUND: Despite total thyroidectomy (TT) is the most practiced procedure for a preoperatively diagnosed neoplastic lesion, according to the ATA guidelines, many surgeons perform completion thyroidectomy (CT) after hemithyroidectomy for patients with preoperative follicular proliferation/indeterminate cytology who are diagnosed with malignancy. CT has a higher complication rate than the primary procedure. The primary endpoint of our study is to compare the morbidity rate after CT with that after primary TT in patients with follicular proliferation/indeterminate cytology. METHODS: We retrospectively reviewed 237 patients who underwent thyroid surgery from 2009 to 2018 at our institution. We recruited only patients with follicular proliferation/indeterminate cytology and excluded those undergoing lymphadenectomies and thyroidectomies for benign pathology and staged thyroidectomies after intraoperative documentation of a RLN lesion. One hundred eighty-six of these patients underwent TT, and fifty-one underwent CT for the detection of differentiated thyroid cancer at the histological exam. RESULTS: No differences were found in the total complication rates between the two groups (OR 0,76, 95% CI 0.35-1.65, P = 0.49). We did not find any significant differences in the subgroup analysis. In particular, no significant differences were identified for transient hypocalcaemia (OR 1.17, 95% CI 0.44-3.11; P = 0,74), permanent hypocalcaemia (OR 1.04, 95% CI 0.21-5.18; P = 0,95), transient unilateral recurrent laryngeal nerve palsy (OR 0.78, 95% CI 0.21-2.81; P = 0,16), permanent unilateral recurrent laryngeal nerve palsy (OR 1.48, 95% CI 0.28-7.85; P = 0,61), and haematoma (OR 1,84, 95% CI 0,16-20,71; P = 0,61). CONCLUSIONS: CT following hemithyroidectomy can be performed with acceptable morbidity in patients with thyroid nodules with preoperative indeterminate cytology/follicular proliferation.

One Anastomosis Gastric Bypass-Mini Gastric Bypass with Tailored Biliopancreatic Limb Length Formula Relative to Small Bowel Length: Preliminary Results.

BACKGROUND: One Anastomosis Gastric Bypass-Mini Gastric Bypass (OAGB-MGB) is rapidly gaining popularity and is currently being performed by an increasing number of bariatric surgeons worldwide. However, excessive postoperative weight loss and malnutrition still remain a major concern regarding this procedure. The aim of this observational retrospective study was to investigate whether a tailored biliopancreatic limb (BPL) length relative to small bowel length (SBL) is superior to a fixed BPL length of 200 cm in terms of weight loss results and nutritional deficiencies in morbidly obese patients 1 year following OAGB-MGB. MATERIALS AND METHODS: Sixty-four patients who underwent OAGB-MGB were divided into two consecutive groups depending on the BPL length used: fixed 200-cm BPL and tailored BPL groups. Anthropometric measurements (%EWL, TWL, %TWL) and nutritional parameters (vitamin A, vitamin D3, vitamin B12, serum iron, serum albumin, total protein) were compared between the two groups at 1-year follow-up. RESULTS: No statistically significant differences were observed between the patients in two groups in terms of %EWL, TWL, %TWL. The number of patients with deficiencies of vitamin A (p = 0.030), vitamin D3 (p = 0.020), and albumin (p = 0.030) was significantly higher in fixed 200-cm BPL group as compared with tailored BPL group, 1 year following OAGB-MGB. No statistically significant differences were seen between the patients in two groups in terms of vitamin B12, iron, and total protein deficiencies. CONCLUSION: Tailoring BPL length by bypassing about 40% of the SBL seems to be safe and effective. According to preliminary results of this study, a tailored BPL length relative to SBL is even likely to be superior to the fixed 200-cm BPL as it is associated with less nutritional deficiencies while providing similar weight loss results. Further randomized studies with larger sample sizes and longer follow-up periods are necessary to confirm the primary results of this study.

Mast Cells, Angiogenesis and Lymphangiogenesis in Human Gastric Cancer.

Gastric cancer is diagnosed in nearly one million new patients each year and it remains the second leading cause of cancer-related deaths worldwide. Although gastric cancer represents a heterogeneous group of diseases, chronic inflammation has been shown to play a role in tumorigenesis. Cancer development is a multistep process characterized by genetic and epigenetic alterations during tumour initiation and progression. The stromal microenvironment is important in maintaining normal tissue homeostasis or promoting tumour development. A plethora of immune cells (i.e., lymphocytes, macrophages, mast cells, monocytes, myeloid-derived suppressor cells, Treg cells, dendritic cells, neutrophils, eosinophils, natural killer (NK) and natural killer T (NKT) cells) are components of gastric cancer microenvironment. Mast cell density is increased in gastric cancer and there is a correlation with angiogenesis, the number of metastatic lymph nodes and the survival of these patients. Mast cells exert a protumorigenic role in gastric cancer through the release of angiogenic (VEGF-A, CXCL8, MMP-9) and lymphangiogenic factors (VEGF-C and VEGF-F). Gastric mast cells express the programmed death ligands (PD-L1 and PD-L2) which are relevant as immune checkpoints in cancer. Several clinical undergoing trials targeting immune checkpoints could be an innovative therapeutic strategy in gastric cancer. Elucidation of the role of subsets of mast cells in different human gastric cancers will demand studies of increasing complexity beyond those assessing merely mast cell density and microlocalization.

The prognostic value of KRAS and BRAF in stage I-III colorectal cancer. A systematic review.

BACKGROUND: Colorectal cancer (CRC) is one of the leading cause of cancer deaths worldwide. The aetiology of CRC is complex and involves interaction on environmental and genetic factors. The two most important pathways are the EGFR (Epidermal Grow Factor Receptor) signaling pathway, with the involvement of KRAS and BRAF, and the DNA mismatch repair (MMR). Generally, KRAS and BRAF mutations are mutually exclusive. They are both able to cause RAS/RAF/MAPK signaling pathway upregulation and are necessary for CRC development. BRAF mutations confers a poor prognosis in Western CRC patients, particularly in metastatic CRC (mCRC) and its mutations occur in approximately 4-20% CRC, with the vast majority being the V600E hotspot mutation. KRAS mutations are observed in 30- 40% CRC patients and act as predictive markers of resistance to epidermal growth factor receptor (EGFR)-targeted antibodies in metastatic CRC. Initial patient management is defined by TNM stage at diagnosis but in patient with stage II and III CRC, TNM staging alone does not predict outcome in CRC patients who may be eligible for adjuvant chemotherapy. Furthermore, for stage II and III, non-metastatic CRC patients, the prognostic role of BRAF and KRAS mutations is still controversial, particularly comparing microsatellite-unstable (MSI) and - stable tumors (MSS). The aim of this study was to clarify the impact of KRAS/BRAF mutations on prognosis in patients with stage I-III CRC. MATERIALS AND METHODS: A systematic review of literature was undertaken to evaluate the prognostic value of KRAS and BRAF mutations in stage I-III colorectal cancer. Four major databases (PUBMED, EMBASE, WEB OF SCIENCE and COCHRANE LIBRARY) were searched. RESULTS: Ninety-two studies were identified. After screening of titles, abstract and inclusion criteria sixteen articles were included. Of the selected articles, five were prospective, ten were retrospectives studies, and one was a combined retrospective/ prospective study. CONCLUSION: In our opinion, a combination of molecular markers, tumor location with the other clinical-pathological variables and microsatellite status is essential to have a correct prognosis. Nevertheless, this combination could be useful as a predictive factor in stage I-III CRC. KEY WORDS: BRAF, Colorectal Cancer, KRAS, Stage I-III CRC, Translational research.

Sphincter-saving proctectomy for rectal cancer with NO COIL® transanal tube and without ostoma. Clinical outcomes, cost effectiveness and quality of life in the elderly.

BACKGROUND: Colorectal cancer is one of the most common invasive cancers, and it is responsible for considerable physical and psychosocial morbidity specially in older patients. However, only few reports focused on quality of life, cost-effectiveness and clinical outcomes of rectal cancer patients undergone to surgery. This retrospective study compares short-term and long-term outcomes in rectal cancer patients with more and less than 75 years of age. METHODS: Four hundred consecutive patients underwent radical surgery for rectal adenocarcinoma and they were collected in a prospective institutional database and divided into two groups: group 1 (≥75 years, N.=98); group 2 (<75 years, N.=302). Rectal anterior resection (RAR) with sphincter-saving restorative proctectomy and with application of silicone transanal tube NO COIL® 60-80 mm long, was the only procedure considered. Main clinical and pathological data were assessed and compared. RESULTS: Statistically significant differences between the two groups were detected regard to comorbidities and the emergency presentation. Overall survival is lower in patients over 75 age, but cancer-related survival is not different between the two groups. CONCLUSIONS: Although advanced age is associated with higher morbidity and mortality, in our experience, itself is not a contraindication for surgical sphincter-saving proctetomy in rectal cancer patients. The absence of a stoma also improved the cost effectiveness and patients' quality of life in both groups: psychological morbidity, sexuality, levels of anxiety and depression, body image.