Porto-spleno-mesenteric venous thrombosis after elective splenectomy: a retrospective cohort study.

Background: Elective splenectomy is the main treatment for a wide range of haematological diseases. Porto-spleno-mesenteric venous thrombosis represents one of the most severe complications of this procedure. The aim of this study was to evaluate risk factors associated with development of porto-spleno-mesenteric venous thrombosis after elective splenectomy. Methods: All cases of elective splenectomy carried out from April 1st 2017 to January 31st 2023 were included in this single centre retrospective cohort study. Patients' demographics and perioperative data were analysed and correlated with the incidence of postoperative thrombosis. All patients underwent postoperative doppler ultrasound screening for thrombosis. Analysis was performed using SPSS 28, with p-value < 0.05 considered significant. Results: Twenty-two patients (10 women, 12 men) underwent splenectomy during the study period. Indications were: immune thrombocytopenia (n: 6), myeloproliferative disorder (n: 6), hereditary spherocytosis (n: 4), thalassemia (n: 1), lymphoma (n: 1), leukaemia (n: 1), other malignancies (n: 3). Six patients developed porto-spleno-mesenteric venous thrombosis and only 2 of them were symptomatic. Patients were treated with anticoagulation therapy with complete resolution. Analysis identified three main factors associated with thrombosis: spleen diameter (p = 0.03), myeloproliferative disorder (p = 0.02), intraoperative platelet transfusion (p = 0.002) and intraoperative red blood cells transfusion (p = 0.009). Conclusion: Standardized postoperative screening allows prompt diagnosis and treatment of porto-spleno-mesenteric venous thrombosis even in asymptomatic cases. Patient with splenomegaly and affected by myeloproliferative disorder have a greater risk to develop this complication.

Corrigendum: TMEM123 a key player in immune surveillance of colorectal cancer.

[This corrects the article DOI: 10.3389/fimmu.2023.1194087.].

TMEM123 a key player in immune surveillance of colorectal cancer.

Colorectal cancer (CRC) is a leading cause of cancer-associated death. In the tumor site, the interplay between effector immune cells and cancer cells determines the balance between tumor elimination or outgrowth. We discovered that the protein TMEM123 is over-expressed in tumour-infiltrating CD4 and CD8 T lymphocytes and it contributes to their effector phenotype. The presence of infiltrating TMEM123+ CD8+ T cells is associated with better overall and metastasis-free survival. TMEM123 localizes in the protrusions of infiltrating T cells, it contributes to lymphocyte migration and cytoskeleton organization. TMEM123 silencing modulates the underlying signaling pathways dependent on the cytoskeletal regulator WASP and the Arp2/3 actin nucleation complex, which are required for synaptic force exertion. Using tumoroid-lymphocyte co-culture assays, we found that lymphocytes form clusters through TMEM123, anchoring to cancer cells and contributing to their killing. We propose an active role for TMEM123 in the anti-cancer activity of T cells within tumour microenvironment.

Identification of the ideal weight-based indocyanine green dose for fluorescent cholangiography.

BACKGROUND: Ideal visualization of fluorescent cholangiography during laparoscopic cholecystectomy is when maximum fluorescence into biliary ducts and absent signal into liver parenchyma, defined as "signal to background ratio" (SBR), is obtained. Such condition is mainly dependent by indocyanine green (ICG) dose and timing. The aim of this study was to identify the ideal ICG dose to obtain the best possible intraoperative visualization of the extra-hepatic biliary tree. METHODS: The first part of the study was used to define a range of small weight-based ICG dosages using the mathematical function bisection method. During the second part of the study, the midpoint dose of the identified range, was tested in 50 consecutive cholecystectomies using a laser-based fluorescence laparoscopic camera (SynergyID system by Arthrex, Naples, FL, USA). Timing administration was set at 1 h before surgery, since this is the most common situation in clinical practice. Fluorescence intensity of bile ducts and liver parenchyma were assessed both subjectively, by blinded operative surgeon, as well as objectively, using an image analysis software (Fiji plugin), before and after Calot's triangle dissection. RESULTS: Fourteen patients were included in the first part of the study and ICG dose between 0.01191406 and 0.0119873 mg/kg was identified. The second part confirmed previous results after testing the dosage equal to 0.0119 mg/kg (midpoint of the defined range) in 50 consecutive cholecystectomies. Cystic duct was identified in 66 and 100% of cases before and after dissection of Calot's triangle respectively. On the other hand, common bile duct was identified in 82 and 92% before and after dissection respectively. Subjective and objective SBRs confirmed the benefit of the identified ICG dose. CONCLUSION: ICG dose calculated by 0.0119 mg/kg administered one hour before surgery allows an ideal intraoperative visualization of the extra-hepatic biliary tree. REGISTRATION NUMBER: ISRCTN10190039.

Lymph node mapping with ICG near-infrared fluorescence imaging: technique and results.

PURPOSE: Lymphadenectomy represents a fundamental step during gastrointestinal cancer resection, as the removal of an adequate number of lymph nodes is crucial to define the stage of the disease and prognosis. Lymphadenectomy during gastric and colorectal resection and adrenalectomy for cancer are technically demanding and can be associated with risk of bleeding. To date, lymphadenectomy is often performed without any visual aid. Indocyanine green fluorescence for lymph node mapping can provide better intraoperative visualization. The purpose of this review is to report the current evidence on this topic. MATERIALS AND METHODS: A systematic research of the electronic databases Medline, Embase and Google Scholar was conducted from the inception to December 2022. RESULTS: This review summarizes the current evidence of techniques and results of fluorescence guided lymphatic mapping during gastrointestinal and adrenal surgery. CONCLUSION: According to this review, ICG guided lymphadenectomy for gastrointestinal tumours and adrenocortical carcinoma is feasible and safe. In gastrointestinal tumours it allows higher number of harvested lymph nodes.

iNKT cell-neutrophil crosstalk promotes colorectal cancer pathogenesis.

iNKT cells account for a relevant fraction of effector T-cells in the intestine and are considered an attractive platform for cancer immunotherapy. Although iNKT cells are cytotoxic lymphocytes, their functional role in colorectal cancer (CRC) is still controversial, limiting their therapeutic use. Thus, we examined the immune cell composition and iNKT cell phenotype of CRC lesions in patients (n = 118) and different murine models. High-dimensional single-cell flow-cytometry, metagenomics, and RNA sequencing experiments revealed that iNKT cells are enriched in tumor lesions. The tumor-associated pathobiont Fusobacterium nucleatum induces IL-17 and Granulocyte-macrophage colony-stimulating factor (GM-CSF) expression in iNKT cells without affecting their cytotoxic capability but promoting iNKT-mediated recruitment of neutrophils with polymorphonuclear myeloid-derived suppressor cells-like phenotype and functions. The lack of iNKT cells reduced the tumor burden and recruitment of immune suppressive neutrophils. iNKT cells in-vivo activation with α-galactosylceramide restored their anti-tumor function, suggesting that iNKT cells can be modulated to overcome CRC-associated immune evasion. Tumor co-infiltration by iNKT cells and neutrophils correlates with negative clinical outcomes, highlighting the importance of iNKT cells in the pathophysiology of CRC. Our results reveal a functional plasticity of iNKT cells in CRC, suggesting a pivotal role of iNKT cells in shaping the tumor microenvironment, with relevant implications for treatment.

Right Hemicolectomy with Complete Mesocolic Excision Using the Versius Surgical System: A Step-by-Step Guide.

The application of new robotic platforms in colorectal surgery has increased greatly in the last 10 years. New systems have been released and entered the surgical panorama, broadening the technological offer. Robotic surgery applied to colorectal oncological surgery has been widely described. Hybrid robotic surgery in right sided colonic cancer has been previously reported. According to the site and local extension of a right-sided colon cancer, a different lymphadenectomy could be required. For more distant and locally advanced tumors a complete mesocolic excision (CME) is indicated. CME for right colon cancer is a complex operation compared to standard right hemicolectomy. Therefore a hybrid robotic system may be effectively applied to CME during a minimally-invasive right hemicolectomy to improve the dissection accuracy. Here we report a step-by-step hybrid laparoscopic/robotic right hemicolectomy with CME performed with the Versius Surgical System, a tele-operated surgical robotic system intended for the use of robotic assisted surgery.

Multicentric validation of EndoDigest: a computer vision platform for video documentation of the critical view of safety in laparoscopic cholecystectomy.

BACKGROUND: A computer vision (CV) platform named EndoDigest was recently developed to facilitate the use of surgical videos. Specifically, EndoDigest automatically provides short video clips to effectively document the critical view of safety (CVS) in laparoscopic cholecystectomy (LC). The aim of the present study is to validate EndoDigest on a multicentric dataset of LC videos. METHODS: LC videos from 4 centers were manually annotated with the time of the cystic duct division and an assessment of CVS criteria. Incomplete recordings, bailout procedures and procedures with an intraoperative cholangiogram were excluded. EndoDigest leveraged predictions of deep learning models for workflow analysis in a rule-based inference system designed to estimate the time of the cystic duct division. Performance was assessed by computing the error in estimating the manually annotated time of the cystic duct division. To provide concise video documentation of CVS, EndoDigest extracted video clips showing the 2 min preceding and the 30 s following the predicted cystic duct division. The relevance of the documentation was evaluated by assessing CVS in automatically extracted 2.5-min-long video clips. RESULTS: 144 of the 174 LC videos from 4 centers were analyzed. EndoDigest located the time of the cystic duct division with a mean error of 124.0 ± 270.6 s despite the use of fluorescent cholangiography in 27 procedures and great variations in surgical workflows across centers. The surgical evaluation found that 108 (75.0%) of the automatically extracted short video clips documented CVS effectively. CONCLUSIONS: EndoDigest was robust enough to reliably locate the time of the cystic duct division and efficiently video document CVS despite the highly variable workflows. Training specifically on data from each center could improve results; however, this multicentric validation shows the potential for clinical translation of this surgical data science tool to efficiently document surgical safety.

Management of intraoperative complications during laparoscopic right colectomy.

BACKGROUND: Minimally invasive right colectomy is increasingly performed as standard treatment for diseases of right colon. Complete mesocolic excision has been introduced for cancer treatment to improve oncological results. Both standard and complete mesocolic excision techniques are associated with intraoperative complications. The purpose of this study was to analyze incidence and management of intraoperative complications in patients who underwent laparoscopic right colectomy with complete mesocolic excision in a single institution. METHODS: This is a retrospective study conducted in a single Italian Center from April 2017 to October 2020. Data of non-metastatic cancer patients who underwent laparoscopic right colectomy were collected to analyze onset of intraoperative complications, their management and rate of conversion to open surgery. RESULTS: A total of 92 patients were included in this study. The 1.09% of patients were converted to open surgery due to adhesions and bowel occlusion. The 5.43% of patients had intraoperative complications: bleeding from Henle's trunk, prepancreatic plane and ileocolic artery stump account for 3.26%, gonadal vessel injury for 1.09% and bowel lesion for 1.09%. CONCLUSIONS: Despite the limits of this study, it showed that bleeding is one of the most frequent complications in laparoscopic right colectomy. Bleeding, occlusion and adhesions are most common reasons for conversion to open surgery.

Expression levels of circulating miRNAs as biomarkers during multimodal treatment of rectal cancer - TiMiSNAR-mirna: a substudy of the TiMiSNAR Trial (NCT03962088).

BACKGROUND: Neoadjuvant chemoradiotherapy followed by surgery is the mainstay treatment for locally advanced rectal cancer, leading to significant decrease in tumor size (downsizing) and a shift towards earlier disease stage (downstaging). Extensive histopathological work-up of the tumor specimen after surgery including tumor regression grading and lymph node status helped to visualize individual tumor sensitivity to chemoradiotherapy, retrospectively. As the response to neoadjuvant chemoradiotherapy is heterogeneous, however, valid biomarkers are needed to monitor tumor response. A relevant number of studies aimed to identify molecular markers retrieved from tumor tissue while the relevance of blood-based biomarkers is less stringent assessed. MicroRNAs are currently under investigation to serve as blood-based biomarkers. To date, no screening approach to identify relevant miRNAs as biomarkers in blood of patients with rectal cancer was undertaken. The aim of the study is to investigate the role of circulating miRNAs as biomarkers in those patients included in the TiMiSNAR Trial (NCT03465982). This is a biomolecular substudy of TiMiSNAR Trial (NCT03962088). METHODS: All included patients in the TiMiSNAR Trial are supposed to undergo blood collection at the time of diagnosis, after neoadjuvant treatment, after 1 month from surgery, and after adjuvant chemotherapy whenever indicated. DISCUSSION: TiMiSNAR-MIRNA will evaluate the association of variation between preneoadjuvant and postneoadjuvant expression levels of miRNA with pathological complete response. Moreover, the study will evaluate the role of liquid biopsies in the monitoring of treatment, correlate changes in expression levels of miRNA following complete surgical resection with disease-free survival, and evaluate the relation between changes in miRNA during surveillance and tumor relapse. TRIAL REGISTRATION: Clinicaltrials.gov NCT03962088 . Registered on 23 May 2019.

Laparoscopic Cholecystectomy in the Cirrhotic: Review of Literature on Indications and Technique.

Cholelithiasis is twice more common in patients suffering from liver cirrhosis compared to overall population and in those patients, acute cholecystitis occurs significantly more often. Our goal was to review the literature and to overview the indications, contra-indications, and alternatives in the cirrhotic with biliary stones. We conducted a systematic review of the literature using the key words "Cirrhosis", "cholecystectomy", "laparoscopy"and "indications". Selected articles were reviewed for information specific to indications, contra-indications, and alternatives to laparoscopic cholecystectomy in cirrhotics. Results showed that laparoscopic cholecystectomy might offer several advantages in cirrhotic population, however cholecystectomy can be challenging: specific indications and alternatives to surgery must be discussed case by case. Laparoscopic cholecystectomy can be performed safely in selected patients with cirrhosis; special precautions are warranted regarding pneumoperitoneum pressure, trocar placement and increased safety with Indocyanine-green (ICG) fluorescence cholangiography. Nevertheless, in high-risk cirrhotic patients (Child C) and/or in common bile duct lithiasis endoscopic and non-surgical conservative treatments are preferable.

The risk of COVID-19 transmission by laparoscopic smoke may be lower than for laparotomy: a narrative review.

BACKGROUND: Surgical smoke is a well-recognized hazard in the operating room. At the beginning of the COVID-19 pandemic, surgical societies quickly published guidelines recommending avoiding laparoscopy or to consider open surgery because of the fear of transmission of SARS-CoV-2 through surgical smoke or aerosol. This narrative review of the literature aimed to determine whether there are any differences in the creation of surgical smoke/aerosol between laparoscopy and laparotomy and if laparoscopy may be safer than laparotomy. METHODS: A literature search was performed using the Pubmed, Embase and Google scholar search engines, as well as manual search of the major journals with specific COVID-19 sections for ahead-of-print publications. RESULTS: Of 1098 identified articles, we critically appraised 50. Surgical smoke created by electrosurgical and ultrasonic devices has the same composition both in laparoscopy and laparotomy. SARS-CoV-2 has never been found in surgical smoke and there is currently no data to support its virulence if ever it could be transmitted through surgical smoke/aerosol. CONCLUSION: If laparoscopy is performed in a closed cavity enabling containment of surgical smoke/aerosol, and proper evacuation of smoke with simple measures is respected, and as long as laparoscopy is not contraindicated, we believe that this surgical approach may be safer for the operating team while the patient has the benefits of minimally invasive surgery. Evidence-based research in this field is needed for definitive determination of safety.

Correction to: Standard (8 weeks) vs long (12 weeks) timing to minimally-invasive surgery after NeoAdjuvant Chemoradiotherapy for rectal cancer: a multicenter randomized controlled parallel group trial (TiMiSNAR).

Following publication of the original article [1], the authors reported that the family name of the author, Ludovica Baldari, was misspelled.

Standard (8 weeks) vs long (12 weeks) timing to minimally-invasive surgery after NeoAdjuvant Chemoradiotherapy for rectal cancer: a multicenter randomized controlled parallel group trial (TiMiSNAR).

BACKGROUND: The optimal timing of surgery in relation to chemoradiation is still controversial. Retrospective analysis has demonstrated in the recent decades that the regression of adenocarcinoma can be slow and not complete until after several months. More recently, increasing pathologic Complete Response rates have been demonstrated to be correlated with longer time interval. The purpose of the trial is to demonstrate if delayed timing of surgery after neoadjuvant chemoradiotherapy actually affects pathologic Complete Response and reflects on disease-free survival and overall survival rather than standard timing. METHODS: The trial is a multicenter, prospective, randomized controlled, unblinded, parallel-group trial comparing standard and delayed surgery after neoadjuvant chemoradiotherapy for the curative treatment of rectal cancer. Three-hundred and forty patients will be randomized on an equal basis to either robotic-assisted/standard laparoscopic rectal cancer surgery after 8 weeks or robotic-assisted/standard laparoscopic rectal cancer surgery after 12 weeks. DISCUSSION: To date, it is well-know that pathologic Complete Response is associated with excellent prognosis and an overall survival of 90%. In the Lyon trial the rate of pCR or near pathologic Complete Response increased from 10.3 to 26% and in retrospective studies the increase rate was about 23-30%. These results may be explained on the relationship between radiation therapy and tumor regression: DNA damage occurs during irradiation, but cellular lysis occurs within the next weeks. Study results, whether confirmed that performing surgery after 12 weeks from neoadjuvant treatment is advantageous from a technical and oncological point of view, may change the current pathway of the treatment in those patient suffering from rectal cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT3465982.

T cell neoepitope discovery in colorectal cancer by high throughput profiling of somatic mutations in expressed genes.

OBJECTIVE: Patient-specific (unique) tumour antigens, encoded by somatically mutated cancer genes, generate neoepitopes that are implicated in the induction of tumour-controlling T cell responses. Recent advancements in massive DNA sequencing combined with robust T cell epitope predictions have allowed their systematic identification in several malignancies. DESIGN: We undertook the identification of unique neoepitopes in colorectal cancers (CRCs) by using high-throughput sequencing of cDNAs expressed by standard cancer cell cultures, and by related cancer stem/initiating cells (CSCs) cultures, coupled with a reverse immunology approach not requiring human leukocyte antigen (HLA) allele-specific epitope predictions. RESULTS: Several unique mutated antigens of CRC, shared by standard cancer and related CSC cultures, were identified by this strategy. CD8+ and CD4+ T cells, either autologous to the patient or derived from HLA-matched healthy donors, were readily expanded in vitro by peptides spanning different cancer mutations and specifically recognised differentiated cancer cells and CSC cultures, expressing the mutations. Neoepitope-specific CD8+ T cell frequency was also increased in a patient, compared with healthy donors, supporting the occurrence of clonal expansion in vivo. CONCLUSIONS: These results provide a proof-of-concept approach for the identification of unique neoepitopes that are immunogenic in patients with CRC and can also target T cells against the most aggressive CSC component.

Primary repair or fecal diversion for colorectal injuries after blast: a medical review.

Blast injury is a frequent cause of injury during armed conflicts, and the force of a blast can cause closed colorectal injury and perforation.1 After identification of a blast-related colorectal injury, the surgical options are primary repair or fecal diversion with the option for secondary repair. This structured review was conducted to determine which patients could be treated with primary repair (PR) or with fecal diversion. The review method followed the Prisma Statement method for medical systematic review. All data from the relevant articles were collected in a single database. Articles took into account wars in Bosnia, Iraq and Afghanistan from January 1993 through November 2012. The review was limited due to lack of reported data, hence qualitative analysis was the main review method. The review showed that for patients who do not have associated intra-abdominal injuries (diaphragm, stomach, pancreas, spleen, or kidney) or hemodynamic instability, PR did not result in an increase of complications or mortality.