Human colorectal cancer: upregulation of the adaptor protein Rai in TILs leads to cell dysfunction by sustaining GSK-3 activation and PD-1 expression.

BACKGROUND: The immunosuppressive tumor microenvironment (TME) of colorectal cancer (CRC) is a major hurdle for immune checkpoint inhibitor-based therapies. Hence characterization of the signaling pathways driving T cell exhaustion within TME is a critical need for the discovery of novel therapeutic targets and the development of effective therapies. We previously showed that (i) the adaptor protein Rai is a negative regulator of T cell receptor signaling and T helper 1 (Th1)/Th17 cell differentiation; and (ii) Rai deficiency is implicated in the hyperactive phenotype of T cells in autoimmune diseases. METHODS: The expression level of Rai was measured by qRT-PCR in paired peripheral blood T cells and T cells infiltrating tumor tissue and the normal adjacent tissue in CRC patients. The impact of hypoxia-inducible factor (HIF)-1α on Rai expression was evaluated in T cells exposed to hypoxia and by performing chromatin immunoprecipitation assays and RNA interference assays. The mechanism by which upregulation of Rai in T cells promotes T cell exhaustion were evaluated by flow cytometric, qRT-PCR and western blot analyses. RESULTS: We show that Rai is a novel HIF-1α-responsive gene that is upregulated in tumor infiltrating lymphocytes of CRC patients compared to patient-matched circulating T cells. Rai upregulation in T cells promoted Programmed cell Death protein (PD)-1 expression and impaired antigen-dependent degranulation of CD8+ T cells by inhibiting phospho-inactivation of glycogen synthase kinase (GSK)-3, a central regulator of PD-1 expression and T cell-mediated anti-tumor immunity. CONCLUSIONS: Our data identify Rai as a hitherto unknown regulator of the TME-induced exhausted phenotype of human T cells.

KRAS-related miR-143 expression is associated with lymph node involvement and correlates with outcome in pancreatic adenocarcinoma patients.

Introduction: Pancreatic adenocarcinoma (PC) is one of the most lethal malignancies; even after resection the patients' 5-year disease-free survival (DFS) is lower than 26%. The genetic mutational landscape of PC is dominated by activating KRAS mutations, that have been reported in approximately 90% of cases; however, beyond KRAS - direct mutations, several KRAS-targeting miRNAs appear to be downregulated, strengthening the already activated RAS signaling. In addition, the interplay between miRNAs and RAS includes poorly investigated downstream miRNAs. The aim of this study was to determine the prognostic value of some of these candidate KRAS-related miRNAs. Patients and methods: Between 2015 and 2022, 44 patients with pathologically confirmed PC, who received surgery and were enrolled by the Clinical Oncology Unit, Careggi University Hospital, Florence (Italy). PC Total RNA was extracted from FFPE sections, retro-transcribed and the resulting cDNA was then used for qPCR analysis. A panel of KRAS-related miRNA (miR-155, miR-206 and miR-143) was analyzed. Results: In this observational study patients sex distribution was unequal with 34.1% being male and 65.9% female. The most frequent tumor localization was the head of the pancreas (65.9%) and the pathological stages were pT1-2 (45.5%), pT3 (54.5%), pN0 (22.7%), pN+ (77.3%). Adjuvant therapy was administered to 63.6% of patients; disease recurrence was observed in 69% of cases. Twenty-three patients, whose RNA was of adequate quality, were used in the mRNAs expression studies. When comparing the miRNA expression between PC and a pool of healthy tissues, miR-155 was overexpressed and miR-206 downregulated in PC, while miR-143 expression was unchanged. However, when categorized in low- and high- miR-143 expressing PC (according to the median value), high miR-143 was associated with nodal involvement (pN+) (p=0.029), who in turn was linked with shorter DFS (p=0.009) and overall survival (OS) (p=0.021) compared to pN0. A trend toward inferior DFS was observed for higher expression of miR-206 (p=0.095) and miR-143 (p=0.092). Finally, responders to a first-line treatment for advanced disease had miR-155 overexpressed (p=0.048). Conclusions: miRNAs are involved in PC tumorigenesis and metastatic spread. In light of miR-143 association with lymphatic spread and poor prognosis, a comprehensive analysis of miRNA interplay with KRAS deserves further investigation.

From adenoma to CRC stages: the oral-gut microbiome axis as a source of potential microbial and metabolic biomarkers of malignancy.

BACKGROUND: Approximately 95% of Colorectal cancers (CRC) consist of adenocarcinomas originating from colonic Adenomatous polyps (AP). Increasing importance in CRC occurrence and progression has been attributed to the gut microbiota; however, a huge proportion of microorganisms inhabit the human digestive system. So, to comprehensively study the microbial spatial variations and their role in CRC progression, from AP to the different CRC phases, a holistic vision is imperative, including the simultaneous evaluation of multiple niches from the gastrointestinal system. Through an integrated approach, we identified potential microbial and metabolic biomarkers, able to discriminate human CRC from AP and/or also the different Tumor node metastasis (TNM) staging. In addition, as the microbiota contributes to the production of essential metabolic products detectable in fecal samples, we analysed and compared metabolites obtained from CRC and AP patients by using a Nuclear magnetic resonance (NMR) approach. METHODS: In this observational study, saliva, tissue and stool samples from 61 patients, have been collected, including 46 CRC and 15 AP patients, age and sex-matched, undergoing surgery in 2018 at the Careggi University Hospital (Florence, Italy). First, the microbiota in the three-district between CRC and AP patients has been characterized, as well as in different CRC TNM stages. Subsequently, proton NMR spectroscopy has been used in combination with multivariate and univariate statistical approaches, to define the fecal metabolic profile of a restricted group of CRC and AP patients. RESULTS: CRC patients display a different profile of tissue and fecal microbiota with respect to AP patients. Significant differences have been observed in CRC tissue microbial clades, with a rise of the Fusobacterium genus. In addition, significant taxa increase at the genus level has been observed in stool samples of CRC patients. Furthermore, Fusobacterium found in intestinal tissue has been positively correlated with fecal Parvimonas, for the first time. Moreover, as predicted by metagenomics pathway analysis, a significant increase of lactate (p=0.037) has been observed in the CRC fecal metabolic profiles, and positively correlated with Bifidobacterium (p=0.036). Finally, minor bacterial differences in CRC patients at stage T2 (TNM classification) have been detected, with a raise of the Spirochaetota phylum in CRC samples, with a slight increase of the Alphaproteobacteria class in fecal samples. CONCLUSION: Our results suggest the importance of microbiota communities and oncometabolites in CRC development. Further studies on CRC/AP management with a focus on CRC assessment are needed to investigate novel microbial-related diagnostic tools aimed to improve therapeutic interventions.

A Comparison between Open and Minimally Invasive Techniques for the Resection of Colorectal Liver Metastasis.

The liver is the most common site of colorectal cancer metastasis. Liver surgery is a cornerstone in treatment, with progressive expansion of minimally invasive surgery (MIS). This study aims to compare short- and long-term outcomes of open surgery and MIS for the treatment of colorectal adenocarcinoma liver metastasis during the first three years of increasing caseload and implementation of MIS use in liver surgery. All patients treated between November 2018 and August 2021 at Careggi Teaching Hospital in Florence, Italy, were prospectively entered into a database and retrospectively reviewed. Fifty-one patients were resected (41 open, 10 MIS). Considering that patients with a significantly higher number of lesions underwent open surgery and operative results were similar, postoperative morbidity rate and length of hospital stay were significantly higher in the open group. No differences were found in the pathological specimen. The postoperative mortality rate was 2%. Mean overall survival and disease-free survival were 46 months (95% CI 42-50) and 22 months (95% CI 15.6-29), respectively. The use of minimally invasive techniques in liver surgery is safe and feasible if surgeons have adequate expertise. MIS and parenchymal sparing resections should be preferred whenever technically feasible.

Preliminary Analysis of the Presence of Bacterial Azurin Coding Gene in CRC Patients and Correlation with the Microbiota Composition.

BACKGROUND: Azurin, a bacterial cupredoxin firstly isolated from the bacterium Pseudomonas aeruginosa, is considered a potential alternative therapeutic tool against different types of cancer. AIMS: In this work we have explored the relationship possibly existing between azurin and colorectal cancer (CRC), in light of the evidence that microbial imbalance can lead to CRC progression. METHODOLOGY/RESULTS: To this aim, the presence of azurin coding gene in the DNA extracted from saliva, stool, and biopsy samples of 10 CRC patients and 10 healthy controls was evaluated by real-time PCR using primers specifically designed to target the azurin coding gene from different bacterial groups. The correlation of the previously obtained microbiota data with real-time PCR results evidenced a "preferential" enrichment of seven bacterial groups in some samples than in others, even though no statistical significance was detected between controls and CRC. The subset of azurin gene-harbouring bacterial groups was representative of the entire community. CONCLUSIONS: Despite the lack of statistical significance between healthy and diseased patients, HTS data analysis highlighted a kind of "preferential" enrichment of seven bacterial groups harbouring the azurin gene in some samples than in others.

Evaluating the best treatment for multifocal hepatocellular carcinoma: A propensity score-matched analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common tumour often diagnosed with a multifocal presentation. Patients with multifocal HCC represent a heterogeneous group. Although Trans-Arterial ChemoEmbolization (TACE) is the most frequently employed treatment for these patients, previous data suggested that liver resection (LR) could be a safe and effective procedure. AIM: To compare LR and TACE in patients with multifocal HCC in terms of procedure-related morbidity and oncologic outcomes. METHODS: All patients with multifocal HCC who underwent LR or TACE as the first procedure between May 2011 and March 2021 were enrolled. The decision to perform surgery or TACE was made after a multidisciplinary team evaluation. Only patients in Child-Pugh class A or B7 and stage B (according to the Barcelona Clinic Liver Cancer staging system, without severe portal hypertension, vascular invasion, or extrahepatic spread) were included in the final analysis. Propensity score matching was used to adjust the baseline differences between patients undergoing LR and the TACE group [number and diameter of lesions, presence of cirrhosis, alpha-fetoprotein (AFP) levels, and Model for End-Stage Liver Disease score]. The Kaplan-Meier method was used to estimate overall survival (OS) and disease-free survival (DFS). The outcomes of LR and TACE were compared using the log-rank test. RESULTS: After matching, 30 patients were eligible for the final analysis, 15 in each group. Morbidity rates were 42.9% and 40% for LR and TACE, respectively (P = 0.876). Median OS was not different in the LR and TACE groups (53 mo vs 18 mo, P = 0.312), while DFS was significantly longer with LR (19 mo vs 0 mo, P = 0.0001). Subgroup analysis showed that patients in the Italian Liver Cancer (ITA.LI.CA) B2 stage, with AFP levels lower than 400 ng/mL, less than 3 lesions, and lesions bigger than 41 mm, benefited more from LR in terms of DFS. Patients classified as ITA.LI.CA B3, with AFP levels higher than 400 ng/mL and with more than 3 lesions, appeared to receive more benefit from TACE in terms of OS. CONCLUSION: In a small cohort of patients with multifocal HCC, LR confers longer DFS compared with TACE, with similar OS and post-procedural morbidity.

Impact of microbiota-immunity axis in pancreatic cancer management.

The microbiota impact on human diseases is well-known, and a growing body of literature is providing evidence about the complex interplay between microbiota-immune system-human physiology/pathology, including cancers. Together with the defined risk factors (e.g., smoke habits, diet, diabetes, and obesity), the oral, gut, biliary, and intrapancreatic microbiota contribute to pancreatic cancer development through different pathways including the interaction with the immune system. Unfortunately, a great majority of the pancreatic cancer patients received a diagnosis in advanced stages not amenable to be radically treated and potentially cured. Given the poor pancreatic cancer prognosis, complete knowledge of these complicated relationships could help researchers better understand the disease pathogenesis and thus provide early potential non-invasive biomarkers, new therapeutic targets, and tools for risk stratification that might result in greater therapeutic possibilities and eventually in a better and longer patient survival.

A comparative study of carbonic anhydrase activity in lymphocytes from colorectal cancer tissues and adjacent healthy counterparts.

Several carbonic anhydrase (CA, EC 4.2.1.1) isoforms play an essential role in processes connected to tumorigenesis, as they efficiently accelerate the hydration of carbon dioxide to bicarbonate and proton. In this context, examples are CA IX and CA XII, which were proved to be upregulated in many solid malignancies. On the other hand, cancer and the immune system are inextricably linked, and targeting the immune checkpoints recently was shown to efficiently improve the treatment of malignancies. In this study, we have investigated the expression of CA isoforms in tumour-infiltrating lymphocytes (TILs) that, according to the immunosurveillance theory, were suggested to have a crucial role in the development of colorectal cancer (CRC). T lymphocytes isolated from healthy surrounding mucosa showed a higher CA activity compared to those present in tumour and peripheral blood in the same patients. CA I and II were confirmed as enzyme isoforms involved in the process, as determined by proteomic analysis of corresponding TIL samples. These preliminary findings suggest a dysregulation of the local immune response in the CRC tissues and a loss of effective anticancer mechanisms mediated by CAs therein.

The emerging role of immunotherapy in biliary tract cancer: a review of new evidence and predictive biomarkers.

Biliary tract cancers (BTCs) are frequently diagnosed in advanced stages and are highly lethal. Immunotherapy may play a role in the treatment of these patients. Promising results come from monotherapy or combination therapy studies in pretreated patients. In addition, several studies have demonstrated the safety and efficacy of immune checkpoint inhibitors (ICIs) in combination with chemotherapy in treatment-naive patients. Numerous biomarkers have been investigated to define their predictive role in response to ICIs. However, the full extent of the benefit of immunotherapies has not yet been fully established and, except for high microsatellite instability status, no other biomarkers were uniquely predictive of response to ICIs.

Gut microbiota and immune system in liver cancer: Promising therapeutic implication from development to treatment.

Liver cancer is a leading cause of death worldwide, and hepatocellular carcinoma (HCC) is the most frequent primary liver tumour, followed by cholangiocarcinoma. Notably, secondary tumours represent up to 90% of liver tumours. Chronic liver disease is a recognised risk factor for liver cancer development. Up to 90% of the patients with HCC and about 20% of those with cholangiocarcinoma have an underlying liver alteration. The gut microbiota-liver axis represents the bidirectional relationship between gut microbiota, its metabolites and the liver through the portal flow. The interplay between the immune system and gut microbiota is also well-known. Although primarily resulting from experiments in animal models and on HCC, growing evidence suggests a causal role for the gut microbiota in the development and progression of chronic liver pathologies and liver tumours. Despite the curative intent of "traditional" treatments, tumour recurrence remains high. Therefore, microbiota modulation is an appealing therapeutic target for liver cancer prevention and treatment. Furthermore, microbiota could represent a non-invasive biomarker for early liver cancer diagnosis. This review summarises the potential role of the microbiota and immune system in primary and secondary liver cancer development, focusing on the potential therapeutic implications.

Fecal metabolomic profiles: A comparative study of patients with colorectal cancer vs adenomatous polyps.

BACKGROUND: Colorectal cancer (CRC), the third most common cause of death in both males and females worldwide, shows a positive response to therapy and usually a better prognosis when detected at an early stage. However, the survival rate declines when the diagnosis is late and the tumor spreads to other organs. Currently, the measures widely used in the clinic are fecal occult blood test and evaluation of serum tumor markers, but the lack of sensitivity and specificity of these markers restricts their use for CRC diagnosis. Due to its high sensitivity and precision, colonoscopy is currently the gold-standard screening technique for CRC, but it is a costly and invasive procedure. Therefore, the implementation of custom-made methodologies including those with minimal invasiveness, protection, and reproducibility is highly desirable. With regard to other screening methods, the screening of fecal samples has several benefits, and metabolomics is a successful method to classify the metabolite shift in living systems as a reaction to pathophysiological influences, genetic modifications, and environmental factors. AIM: To characterize the variation groups and potentially recognize some diagnostic markers, we compared with healthy controls (HCs) the fecal nuclear magnetic resonance (NMR) metabolomic profiles of patients with CRC or adenomatous polyposis (AP). METHODS: Proton nuclear magnetic resonance spectroscopy was used in combination with multivariate and univariate statistical approaches, to define the fecal metabolic profiles of 32 CRC patients, 16 AP patients, and 38 HCs well matched in age, sex, and body mass index. RESULTS: NMR metabolomic analyses revealed that fecal sample profiles differed among CRC patients, AP patients, and HCs, and some discriminatory metabolites including acetate, butyrate, propionate, 3-hydroxyphenylacetic acid, valine, tyrosine and leucine were identified. CONCLUSION: In conclusion, we are confident that our data can be a forerunner for future studies on CRC management, especially the diagnosis and evaluation of the effectiveness of treatments.

A Wearable Sensor-Based Platform for Surgeon Posture Monitoring: A Tool to Prevent Musculoskeletal Disorders.

Surgeons are workers that are particularly prone to the development of musculoskeletal disorders. Recent advances in surgical interventions, such as laparoscopic procedures, have caused a worsening of the scenario, given the harmful static postures that have to be kept for long periods. In this paper, we present a sensor-based platform specifically aimed at monitoring the posture during actual surgical operations. The proposed system adopts a limited number of Inertial Measurement Units (IMUs) to obtain information about spine and neck angles across time. Such a system merges the reliability of sensor-based approaches and the validity of state-of-the-art scoring procedure, such as RULA. Specifically, three IMUs are used to estimate the flexion, lateral bending, and twisting angles of spine and neck. An ergonomic risk index is thus estimated in a time varying fashion borrowing relevant features from the RULA scoring system. The detailed functioning of the proposed systems is introduced, and the assessment results related to a real surgical procedure, consisting of a laparoscopy and mini-laparotomy sections, are shown and discussed. In the exemplary case study introduced, the surgeon kept a high score, indicating the need for an intervention on the working procedures, for a large time fraction. The system allows separately analyzing the contribution of spine and neck, also specifying the angle configuration. It is shown how the proposed approach can provide further information, as related to dynamical analysis, which could be used to enlarge the features taken into account by currently available approaches for ergonomic risk assessment. The proposed system could be adopted both for training purposes, as well as for alerting surgeons during actual surgical operations.

Free Fatty Acids Signature in Human Intestinal Disorders: Significant Association between Butyric Acid and Celiac Disease.

Altered circulating levels of free fatty acids (FFAs), namely short chain fatty acids (SCFAs), medium chain fatty acids (MCFAs), and long chain fatty acids (LCFAs), are associated with metabolic, gastrointestinal, and malignant diseases. Hence, we compared the serum FFA profile of patients with celiac disease (CD), adenomatous polyposis (AP), and colorectal cancer (CRC) to healthy controls (HC). We enrolled 44 patients (19 CRC, 9 AP, 16 CD) and 16 HC. We performed a quantitative FFA evaluation with the gas chromatography-mass spectrometry method (GC-MS), and we performed Dirichlet-multinomial regression in order to highlight disease-specific FFA signature. HC showed a different composition of FFAs than CRC, AP, and CD patients. Furthermore, the partial least squares discriminant analysis (PLS-DA) confirmed perfect overlap between the CRC and AP patients and separation of HC from the diseased groups. The Dirichlet-multinomial regression identified only strong positive association between CD and butyric acid. Moreover, CD patients showed significant interactions with age, BMI, and gender. In addition, among patients with the same age and BMI, being male compared to being female implies a decrease of the CD effect on the (log) prevalence of butyric acid in FFA composition. Our data support GC-MS as a suitable method for the concurrent analysis of circulating SCFAs, MCFAs, and LCFAs in different gastrointestinal diseases. Furthermore, and notably, we suggest for the first time that butyric acid could represent a potential biomarker for CD screening.

Evaluation of prognostic factors and clinicopathological patterns of recurrence after curative surgery for colorectal cancer.

BACKGROUND: Colorectal cancer is a common tumor with a quite high-related mortality. Despite the used curative treatments, patients will develop cancer recurrence in up to 50% of the cases and/or other primary neoplasms. Although most of the recurrences are discovered within 3 years from the first treatment, a small percentage is found after 5 years. The early detection of recurrence is crucial to allow further therapies improving patients' survival. Several follow-up programs have been developed but the optimal one is far from being established. AIM: To evaluation of potential prognostic factors for timing and patterns of recurrence in order to plan tailored follow-up programs. METHODS: Perioperative and long-term data of all consecutive patients surgically treated with curative intent, from January 2006 to June 2009, for colorectal adenocar-cinoma, were retrospectively reviewed to find potential prognostic factors associated with: (1) Recurrence incidence; (2) Incidence of an early (within 3 years from surgery) or late recurrence; and (3) Different sites of recurrence. In addition, the incidence of other primary neoplasms has been evaluated in a cohort of patients with a minimum potential follow-up of 10 years. RESULTS: Our study included 234 patients. The median follow-up period has been 119 ± 46.2 mo. The recurrence rate has been 25.6%. Patients with a higher chance to develop recurrence had also the following characteristics: Higher levels of preoperative glycemia and carcinoembryonic antigen, highest anaesthesiologists Score score, occlusion, received a complex operation performed with an open technique, after a longer hospital stay, and showed advanced tumors. The independent prognostic factors for recurrence were the hospital stay, N stage 2, and M stage 1 (multivariate analysis). Younger ages were significantly associated with an early recurrence onset. Patients that received intermediate colectomies or segmental resections, having an N stage 2 or American Joint Committee on Cancer stage 3 tumors were also associated with a higher risk of liver recurrence, while metastatic diseases at diagnosis were linked with local recurrence. Neoadjuvant treatments showed lung recurrence. Finally, bigger tumors and higher lymph node ratio were associated with peritoneal recurrence (marginally significant). Thirty patients developed a second malignancy during the follow-up time. CONCLUSION: Several prognostic factors should be considered for tailored follow-up programs, eventually, beyond 5 years from the first treatment.

Current management of intrahepatic cholangiocarcinoma: from resection to palliative treatments.

Background Intrahepatic cholangiocarcinoma (ICC) is the second most common liver primary tumour after hepatocellular carcinoma and represents 20% of all the cholangiocarcinomas. Its incidence is increasing and mortality rates are rising. Surgical resection is the only option to cure the disease, despite the high recurrence rates reported to be up to 80%. Intrahepatic recurrences may be still treated with curative intent in a small percentage of the patients. Unfortunately, due to lack of specific symptoms, most patients are diagnosed in a late stage of disease and often unsuitable for resection. Liver transplantation for ICC is still controversial. After the first published poor results, improving outcomes have been reported in highly selected cases, including locally advanced ICC treated with neoadjuvant chemotherapy, when successful in controlling tumour progression. Thus, liver transplantation should be considered a possible option within study protocols. When surgical management is not possible, palliative treatments include chemotherapy, radiotherapy and loco-regional treatments such as radiofrequency ablation, trans-arterial chemoembolization or radioembolization. Conclusions This update on the management of ICC focusses on surgical treatments. Known and potential prognostic factors are highlighted in order to assist in treatment selection.

Role of gut microbiota-immunity axis in patients undergoing surgery for colorectal cancer: Focus on short and long-term outcomes.

Human body is colonized by a huge amount of microorganisms mostly located in the gastrointestinal tract. These dynamic communities, the environment and their metabolites constitute the microbiota. Growing data suggests a causal role of a dysbiotic microbiota in several pathologies, such as metabolic and neurological disorders, immunity dysregulations and cancer, especially the well-studied colorectal cancer development. However, many were preclinical studies and a complete knowledge of the pathogenetic mechanisms in humans is still absent. The gut microbiota can exert direct or indirect effects in different phases of colorectal cancer genesis. For example, Fusobacterium nucleatum promotes cancer through cellular proliferation and some strains of Escherichia coli and Bacteroides fragilis produce genotoxins. However, dysbiosis may also cause a pro-inflammatory state and the stimulation of a Th17 response with IL-17 and IL-22 secretion that have a pro-oncogenic activity, as demonstrated for Fusobacterium nucleatum. Microbiota has a crucial role in several stages of postoperative course; dysbiosis in fact seems related with surgical site infections and Enterococcus faecalis (and other collagenase-producers microbes) are suggested as a cause of anastomotic leak. Consequently, unbalanced presence of some species, together with altered immune response may also have a prognostic role. Microbiota has also a substantial role in effectiveness of chemotherapy, chemoresistance and in the related side effects. In other words, a complete knowledge of the fine pathological mechanisms of gut microbiota may provide a wide range of new diagnostic tools other than therapeutic targets in the light of tailored medicine.

Inferior vena cava resection and reconstruction with a peritoneal patch for a leiomyosarcoma: A case report.

INTRODUCTION: Leiomyosarcomas (LMs) of the inferior vena cava (IVC) are very rare neoplasms seldom reported in the literature. The majority of patients does not present with specific abdominal pain and IVC LMs are used to become symptomatic with the increase of tumor volume. The role of chemotherapy or radiotherapy is not yet defined and surgical resection seems to be the only chance to improve survival rates. PRESENTATION OF CASE: We present a case of a 58-year-old female with a recent diagnosis of IVC LM who underwent surgery with a partial resection of the anterior wall of the vein using a lateral and partial vein clamping. The primary repair of the defect could result in stricture of the vein, so a parietal peritoneum patch was used for the vein reconstruction. The postoperative course was uneventful. DISCUSSION: Actual evidence suggests that vascular sarcomas have limited responsiveness to cytotoxic chemotherapy and chemoradiotherapy, so surgery is the treatment of choice. Major surgery entailing multivisceral and complex vascular resection is usually necessary to achieve negative margins and accurate vascular reconstruction techniques are mandatory to avoid serious circulatory complications. Different kinds of graft (biological or synthetics) are available for the reconstruction, with intrinsic advantages and limitations. The use of peritoneal patches seems a valid and cheap option for vascular reconstruction and it is gaining great attention in recent years. CONCLUSION: This case demonstrates that peritoneal graft could be a safe option to manage IVC defects in expert hands. A brief review of literature is also included.

Preliminary Results of an Exercise Program After Laparoscopic Resective Colorectal Cancer Surgery in Non-Metastatic Adenocarcinoma: A Pilot Study of a Randomized Control Trial.

Performing physical exercise after a colorectal cancer diagnosis is associated with lower mortality related to the tumor itself. In order to improve physical recovery after elective surgery, there are no specific exercise protocols after discharge from the hospital. The purpose of this study is to show the preliminary results of an exercise program after colorectal cancer surgery. Six patients with non-metastatic colorectal adenocarcinoma addressed to respective laparoscopic were randomly assigned to a mixed supervised/home-based exercise program for six months and compared to a control group without exercise. To assess the effectiveness of the program, functional and body composition parameters were evaluated. Three months after surgery, the exercise group increased flexibility (p < 0.01, ES = 0.33), strength of lower limbs (p < 0.01, ES = 0.42) and aerobic capacity (p < 0.01, ES = 0.28). After surgery, the six patients experienced a significant reduction in body mass index (BMI) and free fat mass. More specifically, fat mass reached the lowest values, with a concomitant increase in cell mass after six months (p < 0.01, ES = 0.33). This did not occur in the control group. Colorectal cancer treatment induces a reduction in physical function, particularly during the first six months after treatment. A mixed exercise approach appears promising in countering this process after colorectal cancer surgery.

Significant and Conflicting Correlation of IL-9 With Prevotella and Bacteroides in Human Colorectal Cancer.

Background and aim: Gut microbiota (GM) can support colorectal cancer (CRC) progression by modulating immune responses through the production of both immunostimulatory and/or immunosuppressive cytokines. The role of IL-9 is paradigmatic because it can either promote tumor progression in hematological malignancies or inhibit tumorigenesis in solid cancers. Therefore, we investigate the microbiota-immunity axis in healthy and tumor mucosa, focusing on the correlation between cytokine profile and GM signature. Methods: In this observational study, we collected tumor (CRC) and healthy (CRC-S) mucosa samples from 45 CRC patients, who were undergoing surgery in 2018 at the Careggi University Hospital (Florence, Italy). First, we characterized the tissue infiltrating lymphocyte subset profile and the GM composition. Subsequently, we evaluated the CRC and CRC-S molecular inflammatory response and correlated this profile with GM composition, using Dirichlet multinomial regression. Results: CRC samples displayed higher percentages of Th17, Th2, and Tregs. Moreover, CRC tissues showed significantly higher levels of MIP-1α, IL-1α, IL-1ß, IL-2, IP-10, IL-6, IL-8, IL-17A, IFN-γ, TNF-α, MCP-1, P-selectin, and IL-9. Compared to CRC-S, CRC samples also showed significantly higher levels of the following genera: Fusobacteria, Proteobacteria, Fusobacterium, Ruminococcus2, and Ruminococcus. Finally, the abundance of Prevotella spp. in CRC samples negatively correlated with IL-17A and positively with IL-9. On the contrary, Bacteroides spp. presence negatively correlated with IL-9. Conclusions: Our data consolidate antitumor immunity impairment and the presence of a distinct microbiota profile in the tumor microenvironment compared with the healthy mucosa counterpart. Relating the CRC cytokine profile with GM composition, we confirm the presence of bidirectional crosstalk between the immune response and the host's commensal microorganisms. Indeed, we document, for the first time, that Prevotella spp. and Bacteroides spp. are, respectively, positively and negatively correlated with IL-9, whose role in CRC development is still under debate.

Evaluation and comparison of short chain fatty acids composition in gut diseases.

BACKGROUND: An altered (dysbiosis) and unhealthy status of the gut microbiota is usually responsible for a reduction of short chain fatty acids (SCFAs) concentration. SCFAs obtained from the carbohydrate fermentation processes are crucial in maintaining gut homeostasis and their determination in stool samples could provide a faster, reliable and cheaper method to highlight the presence of an intestinal dysbiosis and a biomarker for various gut diseases. We hypothesize that different intestinal diseases, such as celiac disease (CD), adenomatous polyposis (AP) and colorectal cancer (CRC) could display a particular fecal SCFAs' signature. AIM: To compare the fecal SCFAs' profiles of CD, AP, CRC patients and healthy controls, using the same analytical method. METHODS: In this cross-sectional study, we defined and compared the SCFAs' concentration in fecal samples of 9 AP, 16 CD, 19 CRC patients and 16 healthy controls (HC). The SCFAs' analysis were performed using a gas-chromatography coupled with mass spectrometry method. Data analysis was carried out using Wilcoxon rank-sum test to assess pairwise differences of SCFAs' profiles, partial least squares-discriminate analysis (PLS-DA) to determine the status membership based on distinct SCFAs' profiles, and Dirichlet regression to determine factors influencing concentration levels of SCFAs. RESULTS: We have not observed any difference in the SCFAs' amount and composition between CD and healthy control. On the contrary, the total amount of SCFAs was significantly lower in CRC patients compared to HC (P = 0.044) and CD (P = 0.005). Moreover, the SCFAs' percentage composition was different in CRC and AP compared to HC. In detail, HC displayed higher percentage of acetic acid (P value = 1.3 × 10-6) and a lower amount of butyric (P value = 0.02192), isobutyric (P value = 7.4 × 10-5), isovaleric (P value = 0.00012) and valeric (P value = 0.00014) acids compared to CRC patients. AP showed a lower abundance of acetic acid (P value = 0.00062) and higher percentages of propionic (P value = 0.00433) and isovaleric (P value = 0.00433) acids compared to HC. Moreover, AP showed higher levels of propionic acid (P value = 0.03251) and a lower level of isobutyric acid (P value = 0.00427) in comparison to CRC. The PLS-DA model demonstrated a significant separation of CRC and AP groups from HC, although some degree of overlap was observed between CRC and AP. CONCLUSION: Analysis of fecal SCFAs shows the potential to provide a non-invasive means of diagnosis to detect patients with CRC and AP, while CD patients cannot be discriminated from healthy subjects.