Maternal obesity increases the risk of hepatocellular carcinoma through the transmission of an altered gut microbiome.

Background & Aims: Emerging evidence suggests that maternal obesity negatively impacts the health of offspring. Additionally, obesity is a risk factor for hepatocellular carcinoma (HCC). Our study aims to investigate the impact of maternal obesity on the risk for HCC development in offspring and elucidate the underlying transmission mechanisms. Methods: Female mice were fed either a high-fat diet (HFD) or a normal diet (ND). All offspring received a ND after weaning. We studied liver histology and tumor load in a N-diethylnitrosamine (DEN)-induced HCC mouse model. Results: Maternal obesity induced a distinguishable shift in gut microbial composition. At 40 weeks, female offspring of HFD-fed mothers (HFD offspring) were more likely to develop steatosis (9.43% vs. 3.09%, p = 0.0023) and fibrosis (3.75% vs. 2.70%, p = 0.039), as well as exhibiting an increased number of inflammatory infiltrates (4.8 vs. 1.0, p = 0.018) and higher expression of genes involved in fibrosis and inflammation, compared to offspring of ND-fed mothers (ND offspring). A higher proportion of HFD offspring developed liver tumors after DEN induction (79.8% vs. 37.5%, p = 0.0084) with a higher mean tumor volume (234 vs. 3 µm3, p = 0.0041). HFD offspring had a significantly less diverse microbiota than ND offspring (Shannon index 2.56 vs. 2.92, p = 0.0089), which was rescued through co-housing. In the principal component analysis, the microbiota profile of co-housed animals clustered together, regardless of maternal diet. Co-housing of HFD offspring with ND offspring normalized their tumor load. Conclusions: Maternal obesity increases female offspring's susceptibility to HCC. The transmission of an altered gut microbiome plays an important role in this predisposition. Impact and implications: The worldwide incidence of obesity is constantly rising, with more and more children born to obese mothers. In this study, we investigate the impact of maternal diet on gut microbiome composition and its role in liver cancer development in offspring. We found that mice born to mothers with a high-fat diet inherited a less diverse gut microbiome, presented chronic liver injury and an increased risk of developing liver cancer. Co-housing offspring from normal diet- and high-fat diet-fed mothers restored the gut microbiome and, remarkably, normalized the risk of developing liver cancer. The implementation of microbial screening and restoration of microbial diversity holds promise in helping to identify and treat individuals at risk to prevent harm for future generations.

Abdominal surgery in patients with chronic noncirrhotic extra hepatic portal vein obstruction: A multicenter retrospective study.

BACKGROUND AIMS: In patients with noncirrhotic chronic extra-hepatic portal vein obstruction (EHPVO), data on morbimortality of abdominal surgery are scarce. APPROACH RESULTS: We retrospectively analyzed the charts of 76 patients (78 interventions) with EHPVO undergoing abdominal surgery within the VALDIG network. Fourteen percent of the patients had ≥1 major bleeding (unrelated to portal hypertension) and 21% had ≥1 Dindo-Clavien grade ≥3 postoperative complication within 1 month after surgery. Fifteen percent had ≥1 portal hypertension related complication within 3 months after surgery. Three patients died within 12 months after surgery. An unfavorable outcome (i.e. ≥1 above-mentioned complications or death) occurred in 37% of the patients and was associated with a history of ascites and with non-wall, non-cholecystectomy surgical intervention: 17% of the patients with none of these features had an unfavorable outcome, versus 48% and 100% when one or both features were present, respectively. We then compared 63/76 EHPVO patients with 126 matched (2:1) control patients without EHPVO but with similar surgical interventions. As compared with control patients, incidence of major bleeding (p<0.001) and portal-hypertension related complication (p<0.001) was significantly higher in patients with EHPVO, but not that of grade ≥3 postoperative complication nor of death. The incidence of unfavorable post-operative outcome was significantly higher in patients with EHPVO than in those without (33% vs. 18%, p=0.01). CONCLUSION: Patients with EHPVO are at high-risk of major peri- or postoperative bleeding and postoperative complications, especially in those with ascites or undergoing surgery other than wall surgery or cholecystectomy.

Robotic versus laparoscopic right hemicolectomy: a systematic review of the evidence.

Robotics may facilitate the realization of fully minimally invasive right hemicolectomy, including intra-corporeal anastomosis and off-midline extraction, when compared to laparoscopy. Our aim was to compare laparoscopic right hemicolectomy with robotic right hemicolectomy in terms of peri-operative outcomes. MEDLINE was searched for original studies comparing laparoscopic right hemicolectomy with robotic right hemicolectomy in terms of peri-operative outcomes. The systematic review complied with the PRISMA 2020 recommendations. Variables related to patients' demographics, surgical procedures, post-operative recovery and pathological outcomes were collected and qualitatively assessed. Two-hundred and ninety-three publications were screened, 277 were excluded and 16 were retained for qualitative analysis. The majority of included studies were observational and of limited sample size. When the type of anastomosis was left at surgeon's discretion, intra-corporeal anastomosis was favoured in robotic right hemicolectomy (4/4 studies). When compared to laparoscopy, robotics allowed harvesting more lymph nodes (4/15 studies), a lower conversion rate to open surgery (5/14 studies), a shorter time to faeces (2/3 studies) and a shorter length of stay (5/14 studies), at the cost of a longer operative time (13/14 studies). Systematic review of existing studies, which are mostly non-randomized, suggests that robotic surgery may facilitate fully minimally invasive right hemicolectomy, including intra-corporeal anastomosis, and offer improved post-operative recovery.

Score prediction of anastomotic leak in colorectal surgery: a systematic review.

OBJECTIVE: Predicting the risk of anastomotic leak (AL) is of importance when defining the optimal surgical strategy in colorectal surgery. Our objective was to perform a systematic review of existing scores in the field. METHODS: We followed the PRISMA checklist (S1 Checklist). Medline, Cochrane Central and Embase were searched for observational studies reporting on scores predicting AL after the creation of a colorectal anastomosis. Studies reporting only validation of existing scores and/or scores based on post-operative variables were excluded. PRISMA 2020 recommendations were followed. Qualitative analysis was performed. RESULTS: Eight hundred articles were identified. Seven hundred and ninety-one articles were excluded after title/abstract and full-text screening, leaving nine studies for analysis. Scores notably included the Colon Leakage Score, the modified Colon Leakage Score, the REAL score, www.anastomoticleak.com and the PROCOLE score. Four studies (44.4%) included more than 1.000 patients and one extracted data from existing studies (meta-analysis of risk factors). Scores included the following pre-operative variables: age (44.4%), sex (77.8%), ASA score (66.6%), BMI (33.3%), diabetes (22.2%), respiratory comorbidity (22.2%), cardiovascular comorbidity (11.1%), liver comorbidity (11.1%), weight loss (11.1%), smoking (33.3%), alcohol consumption (33.3%), steroid consumption (33.3%), neo-adjuvant treatment (44.9%), anticoagulation (11.1%), hematocrit concentration (22.2%), total proteins concentration (11.1%), white blood cell count (11.1%), albumin concentration (11.1%), distance from the anal verge (77.8%), number of hospital beds (11.1%), pre-operative bowel preparation (11.1%) and indication for surgery (11.1%). Scores included the following peri-operative variables: emergency surgery (22.2%), surgical approach (22.2%), duration of surgery (66.6%), blood loss/transfusion (55.6%), additional procedure (33.3%), operative complication (22.2%), wound contamination class (1.11%), mechanical anastomosis (1.11%) and experience of the surgeon (11.1%). Five studies (55.6%) reported the area under the curve (AUC) of the scores, and four (44.4%) included a validation set. CONCLUSION: Existing scores are heterogeneous in the identification of pre-operative variables allowing predicting AL. A majority of scores was established from small cohorts of patients which, considering the low incidence of AL, might lead to miss potential predictors of AL. AUC is seldom reported. We recommend that new scores to predict the risk of AL in colorectal surgery to be based on large cohorts of patients, to include a validation set and to report the AUC.

[Abdominal surgery: what's new in 2023]. / Chirurgie viscérale: ce qui a changé en 2023.

In 2023, robotic surgery has witnessed an expansion in the number of surgical procedures and in the number of platforms on the market. We illustrate the phenomenon, by exploring parietal, œso-gastric and liver robotic surgery. Surgical innovation aligns with advancements in oncology. Immunotherapy now enables "watch and wait" strategies for patients with colorectal cancer, and decreases recurrence rate and improves survival after liver surgery for hepatocellular carcinoma and œso-gastric surgery. The multidisciplinary field of obesity management has seen the development of new medications, diversifying the treatment options, while surgery continues to deliver the best weight-loss outcomes.

En 2023, la chirurgie robotique a poursuivi son expansion avec une augmentation du nombre d'interventions et la mise sur le marché de nouvelles plateformes. Ce phénomène est illustré dans cet article par la description des chirurgies robotique pariétale, œsogastrique et hépatique. L'innovation en chirurgie accompagne aussi celle de l'oncologie. L'immunothérapie permet maintenant une stratégie « watch and wait ¼ chez les patients avec un cancer colorectal, diminue le risque de récidive et améliore la survie après chirurgie hépatique pour un carcinome hépatocellulaire et chirurgie œsogastrique. Le domaine multidisciplinaire de la prise en charge de l'obésité a aussi vu l'arrivée de nouveaux traitements médicamenteux, qui viennent diversifier les options thérapeutiques, où la chirurgie continue d'apporter les meilleurs résultats en termes de perte de poids.

International survey on opinions and use of robot-assisted and laparoscopic minimally invasive pancreatic surgery: 5-year follow up.

BACKGROUND: Evidence on the value of minimally invasive pancreatic surgery (MIPS) has been increasing but it is unclear how this has influenced the view of pancreatic surgeons on MIPS. METHODS: An anonymous survey was sent to members of eight international Hepato-Pancreato-Biliary Associations. Outcomes were compared with the 2016 international survey. RESULTS: Overall, 315 surgeons from 47 countries participated. The median volume of pancreatic resections per center was 70 (IQR 40-120). Most surgeons considered minimally invasive distal pancreatectomy (MIDP) superior to open (ODP) (94.6%) and open pancreatoduodenectomy (OPD) superior to minimally invasive (MIPD) (67.9%). Since 2016, there has been an increase in the number of surgeons performing both MIDP (79%-85.7%, p = 0.024) and MIPD (29%-45.7%, p < 0.001), and an increase in the use of the robot-assisted approach for both MIDP (16%-45.6%, p < 0.001) and MIPD (23%-47.9%, p < 0.001). The use of laparoscopy remained stable for MIDP (91% vs. 88.1%, p = 0.245) and decreased for MIPD (51%-36.8%, p = 0.024). CONCLUSION: This survey showed considerable changes of MIPS since 2016 with most surgeons considering MIDP superior to ODP and an increased use of robot-assisted MIPS. Surgeons prefer OPD and therefore the value of MIPD remains to be determined in randomized trials.

Global benchmarks in primary robotic bariatric surgery redefine quality standards for Roux-en-Y gastric bypass and sleeve gastrectomy.

BACKGROUND: Whether the benefits of the robotic platform in bariatric surgery translate into superior surgical outcomes remains unclear. The aim of this retrospective study was to establish the 'best possible' outcomes for robotic bariatric surgery and compare them with the established laparoscopic benchmarks. METHODS: Benchmark cut-offs were established for consecutive primary robotic bariatric surgery patients of 17 centres across four continents (13 expert centres and 4 learning phase centres) using the 75th percentile of the median outcome values until 90 days after surgery. The benchmark patients had no previous laparotomy, diabetes, sleep apnoea, cardiopathy, renal insufficiency, inflammatory bowel disease, immunosuppression, history of thromboembolic events, BMI greater than 50 kg/m2, or age greater than 65 years. RESULTS: A total of 9097 patients were included, who were mainly female (75.5%) and who had a mean(s.d.) age of 44.7(11.5) years and a mean(s.d.) baseline BMI of 44.6(7.7) kg/m2. In expert centres, 13.74% of the 3020 patients who underwent primary robotic Roux-en-Y gastric bypass and 5.9% of the 4078 patients who underwent primary robotic sleeve gastrectomy presented with greater than or equal to one complication within 90 postoperative days. No patient died and 1.1% of patients had adverse events related to the robotic platform. When compared with laparoscopic benchmarks, robotic Roux-en-Y gastric bypass had lower benchmark cut-offs for hospital stay, postoperative bleeding, and marginal ulceration, but the duration of the operation was 42 min longer. For most surgical outcomes, robotic sleeve gastrectomy outperformed laparoscopic sleeve gastrectomy with a comparable duration of the operation. In robotic learning phase centres, outcomes were within the established benchmarks only for low-risk robotic Roux-en-Y gastric bypass. CONCLUSION: The newly established benchmarks suggest that robotic bariatric surgery may enhance surgical safety compared with laparoscopic bariatric surgery; however, the duration of the operation for robotic Roux-en-Y gastric bypass is longer.

Correction: Balaphas et al. Cell Therapy for Anal Sphincter Incontinence: Where Do We Stand? Cells 2021, 10, 2086.

The authors would like to add a new reference to the section "3 [...].

Portosystemic shunting prevents hepatocellular carcinoma in non-alcoholic fatty liver disease mouse models.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is one of the leading cause of hepatocellular carcinoma (HCC). This association is supported by the translocation of bacteria products into the portal system, which acts on the liver through the gut-liver axis. We hypothesize that portosystemic shunting can disrupt this relationship, and prevent NAFLD-associated HCC. METHODS: HCC carcinogenesis was tested in C57BL/6 mice fed a high-fat high-sucrose diet (HFD) and injected with diethylnitrosamine (DEN) at two weeks of age, and in double transgenic LAP-tTA and TRE-MYC (LAP-Myc) mice fed a methionine-choline-deficient diet. Portosystemic shunts were established by transposing the spleen to the sub-cutaneous tissue at eight weeks of age. RESULTS: Spleen transposition led to a consistent deviation of part of the portal flow and a significant decrease in portal pressure. It was associated with a decrease in the number of HCC in both models. This effect was supported by the presence of less severe liver steatosis after 40 weeks, and lower expression levels of liver fatty acid synthase. Also, shunted mice exhibited lower liver oxygen levels, a key factor in preventing HCC as confirmed by the development of less HCCs in mice with hepatic artery ligation. CONCLUSIONS: The present data show that portosystemic shunting prevents NAFLD-associated HCC, utilizing two independent mouse models. This effect is supported by the development of less steatosis, and a restored liver oxygen level. Portal pressure modulation and shunting deserve further exploration as potential prevention/treatment options for NAFLD and HCC.

Sodium Hydrosulfide Treatment During Porcine Kidney Ex Vivo Perfusion and Transplantation.

Background: In rodents, hydrogen sulfide (H2S) reduces ischemia-reperfusion injury and improves renal graft function after transplantation. Here, we hypothesized that the benefits of H2S are conserved in pigs, a more clinically relevant model. Methods: Adult porcine kidneys retrieved immediately or after 60 min of warm ischemia (WI) were exposed to 100 µM sodium hydrosulfide (NaHS) (1) during the hypothermic ex vivo perfusion only, (2) during WI only, and (3) during both WI and ex vivo perfusion. Kidney perfusion was evaluated with dynamic contrast-enhanced MRI. MRI spectroscopy was further employed to assess energy metabolites including ATP. Renal biopsies were collected at various time points for histopathological analysis. Results: Perfusion for 4 h pig kidneys with Belzer MPS UW + NaHS resulted in similar renal perfusion and ATP levels than perfusion with UW alone. Similarly, no difference was observed when NaHS was administered in the renal artery before ischemia. After autotransplantation, no improvement in histologic lesions or cortical/medullary kidney perfusion was observed upon H2S administration. In addition, AMP and ATP levels were identical in both groups. Conclusions: In conclusion, treatment of porcine kidney grafts using NaHS did not result in a significant reduction of ischemia-reperfusion injury or improvement of kidney metabolism. Future studies will need to define the benefits of H2S in human, possibly using other molecules as H2S donors.

European Society of Organ Transplantation (ESOT) Consensus Report on Downstaging, Bridging and Immunotherapy in Liver Transplantation for Hepatocellular Carcinoma.

Liver transplantation offers the best chance of cure for most patients with non-metastatic hepatocellular carcinoma (HCC). Although not all patients with HCC are eligible for liver transplantation at diagnosis, some can be downstaged using locoregional treatments such as ablation and transarterial chemoembolization. These aforementioned treatments are being applied as bridging therapies to keep patients within transplant criteria and to avoid them from dropping out of the waiting list while awaiting a liver transplant. Moreover, immunotherapy might have great potential to support downstaging and bridging therapies. To address the contemporary status of downstaging, bridging, and immunotherapy in liver transplantation for HCC, European Society of Organ Transplantation (ESOT) convened a dedicated working group comprised of experts in the treatment of HCC to review literature and to develop guidelines pertaining to this cause that were subsequently discussed and voted during the Transplant Learning Journey (TLJ) 3.0 Consensus Conference that took place in person in Prague. The findings and recommendations of the working group on Downstaging, Bridging and Immunotherapy in Liver Transplantation for Hepatocellular Carcinoma are presented in this article.

Immunotherapy and Liver Transplantation: A Narrative Review of Basic and Clinical Data.

Immune checkpoint inhibitors (ICIs) have improved the management of patients with intermediate- and advanced-stage HCC, even making some of them potential candidates for liver transplantation. However, acute rejection has been observed after ICI therapy, challenging its safety in transplant settings. We summarize the key basic impact of immune checkpoints on HCC and liver transplantation. We analyze the available case reports and case series on the use of ICI therapy prior to and after liver transplantation. A three-month washout period is desirable between ICI therapy and liver transplantation to reduce the risk of acute rejection. Whenever possible, ICIs should be avoided after liver transplantation, and especially so early after a transplant. Globally, more robust prospective data in the field are required.

Incidence of diverticulitis recurrence after sigmoid colectomy: a retrospective cohort study from a tertiary center and systematic review.

INTRODUCTION: Our aim was to determine the incidence of diverticulitis recurrence after sigmoid colectomy for diverticular disease. METHODS: Consecutive patients who benefited from sigmoid colectomy for diverticular disease from January 2007 to June 2021 were identified based on operative codes. Recurrent episodes were identified based on hospitalization codes and reviewed. Survival analysis was performed and was reported using a Kaplan-Meier curve. Follow-up was censored for last hospital visit and diverticulitis recurrence. The systematic review of the literature was performed according to the PRISMA statement. Medline, Embase, CENTRAL, and Web of Science were searched for studies reporting on the incidence of diverticulitis after sigmoid colectomy. The review was registered into PROSPERO (CRD42021237003, 25/06/2021). RESULTS: One thousand three-hundred and fifty-six patients benefited from sigmoid colectomy. Four hundred and three were excluded, leaving 953 patients for inclusion. The mean age at time of sigmoid colectomy was 64.0 + / - 14.7 years. Four hundred and fifty-eight patients (48.1%) were males. Six hundred and twenty-two sigmoid colectomies (65.3%) were performed in the elective setting and 331 (34.7%) as emergency surgery. The mean duration of follow-up was 4.8 + / - 4.1 years. During this period, 10 patients (1.1%) developed reccurent diverticulitis. Nine of these episodes were classified as Hinchey 1a, and one as Hinchey 1b. The incidence of diverticulitis recurrence (95% CI) was as follows: at 1 year: 0.37% (0.12-1.13%), at 5 years: 1.07% (0.50-2.28%), at 10 years: 2.14% (1.07-4.25%) and at 15 years: 2.14% (1.07-4.25%). Risk factors for recurrence could not be assessed by logistic regression due to the low number of incidental cases. The systematic review of the literature identified 15 observational studies reporting on the incidence of diverticulitis recurrence after sigmoid colectomy, which ranged from 0 to 15% for a follow-up period ranging between 2 months and over 10 years. CONCLUSION: The incidence of diverticulitis recurrence after sigmoid colectomy is of 2.14% at 15 years, and is mostly composed of Hinchey 1a episodes. The incidences reported in the literature are heterogeneous.

[Esophageal cancer: standards and innovations in multidisciplinary treatment]. / Cancer de l'œsophage : standards et innovations du traitement multidisciplinaire.

Esophageal cancer is a severe disease that requires a combined therapeutic approach to improve the prognosis. Once the initial assessment is completed, the patient's case should be discussed in a multidisciplinary conference in a specialized center to decide on an appropriate therapeutic strategy taking into account the stage of the disease and the patient's general condition. Several advances in treatment, both from a surgical technique standpoint, with the advent of minimally invasive and robotic surgery, and from a medical perspective, with the use of immunotherapy under certain conditions, have dramatically improved mortality rates. In this article, we explore the standards and latest innovations in the multimodal treatment of esophageal cancer.

Le cancer de l'œsophage est une pathologie sévère nécessitant une approche thérapeutique combinée afin d'en améliorer le pronostic. Une fois le bilan initial réalisé, le cas du patient doit être discuté lors d'un colloque multidisciplinaire dans un centre spécialisé, afin de décider d'une stratégie thérapeutique adaptée tenant compte du stade de la maladie et de l'état général du patient. Plusieurs avancées en matière de traitement, tant du point de vue technique chirurgical, par l'avènement de la chirurgie minimalement invasive et robotique, que du point de vue médical, par le recours à l'immunothérapie sous certaines conditions, ont permis d'améliorer drastiquement le taux de mortalité. Dans cet article, nous explorons les standards ainsi que les dernières innovations dans le traitement multimodal du cancer de l'œsophage.

One-step totally robotic Hartmann reversal and complex abdominal wall reconstruction with bilateral posterior component separation: a technical note.

AIM: This paper describes a robotic approach to combined gastrointestinal continuity restoration and complex abdominal wall reconstruction after Hartmann's procedure complicated by large midline and parastomal hernias. METHODS: A robotic Hartmann reversal is performed, followed by robotic retromuscular abdominal wall reconstruction of all ventral defects with bilateral posterior component separation using the double-docking approach. Surgical steps are thoroughly described, and the accompanying video highlights critical steps of the procedure, anatomical landmarks and technical details relevant to successful completion. RESULTS: Complete restoration of the anatomy was achieved with an operative time of 6.5 h. Mobilization occured on day 1, and bowels were opened on day 3. Surgical discharge was possible on day 5. No intra-operative surgical complication occurred and follow-up at 6 months showed no recurrence or mid-term complication. CONCLUSION: Combined minimally invasive reconstruction of the gastrointestinal tract and abdominal wall was feasible using a robotic system. In addition, potential advantages of postoperative rehabilitation and reduced surgical site complications are suggested. Prospective evaluation of the technique is ongoing.

Neurometabolic changes in a rat pup model of type C hepatic encephalopathy depend on age at liver disease onset.

Chronic liver disease (CLD) is a serious condition where various toxins present in the blood affect the brain leading to type C hepatic encephalopathy (HE). Both adults and children are impacted, while children may display unique vulnerabilities depending on the affected window of brain development.We aimed to use the advantages of high field proton Magnetic Resonance Spectroscopy (1H MRS) to study longitudinally the neurometabolic and behavioural effects of Bile Duct Ligation (animal model of CLD-induced type C HE) on rats at post-natal day 15 (p15) to get closer to neonatal onset liver disease. Furthermore, we compared two sets of animals (p15 and p21-previously published) to evaluate whether the brain responds differently to CLD according to age onset.We showed for the first time that when CLD was acquired at p15, the rats presented the typical signs of CLD, i.e. rise in plasma bilirubin and ammonium, and developed the characteristic brain metabolic changes associated with type C HE (e.g. glutamine increase and osmolytes decrease). When compared to rats that acquired CLD at p21, p15 rats did not show any significant difference in plasma biochemistry, but displayed a delayed increase in brain glutamine and decrease in total-choline. The changes in neurotransmitters were milder than in p21 rats. Moreover, p15 rats showed an earlier increase in brain lactate and a different antioxidant response. These findings offer tentative pointers as to which neurodevelopmental processes may be impacted and raise the question of whether similar changes might exist in humans but are missed owing to 1H MRS methodological limitations in field strength of clinical magnet.

A new clinical severity score for the management of acute small bowel obstruction in predicting bowel ischemia: a cohort study.

BACKGROUND: Small bowel obstruction (SBO) is a common hospital admission diagnosis. Identification of patients who will require a surgical resection because of a nonviable small bowel remains a challenge. Through a prospective cohort study, the authors aimed to validate risk factors and scores for intestinal resection, and to develop a practical clinical score designed to guide surgical versus conservative management. PATIENTS AND METHODS: All patients admitted for an acute SBO between 2004 and 2016 in the center were included. Patients were divided in three categories depending on the management: conservative, surgical with bowel resection, and surgical without bowel resection. The outcome variable was small bowel necrosis. Logistic regression models were used to identify the best predictors. RESULTS: Seven hundred and thirteen patients were included in this study, 492 in the development cohort and 221 in the validation cohort. Sixty-seven percent had surgery, of which 21% had small bowel resection. Thirty-three percent were treated conservatively. Eight variables were identified with a strong association with small bowel resection: age 70 years of age and above, first episode of SBO, no bowel movement for greater than or equal to 3 days, abdominal guarding, C-reactive protein greater than or equal to 50, and three abdominal computer tomography scanner signs: small bowel transition point, lack of small bowel contrast enhancement, and the presence of greater than 500 ml of intra-abdominal fluid. Sensitivity and specificity of this score were 65 and 88%, respectively, and the area under the curve was 0.84 (95% CI: 0.80-0.89). CONCLUSION: The authors developed and validated a practical clinical severity score designed to tailor management of patients presenting with an SBO.

Platform combining statistical modeling and patient-derived organoids to facilitate personalized treatment of colorectal carcinoma.

BACKGROUND: We propose a new approach for designing personalized treatment for colorectal cancer (CRC) patients, by combining ex vivo organoid efficacy testing with mathematical modeling of the results. METHODS: The validated phenotypic approach called Therapeutically Guided Multidrug Optimization (TGMO) was used to identify four low-dose synergistic optimized drug combinations (ODC) in 3D human CRC models of cells that are either sensitive or resistant to first-line CRC chemotherapy (FOLFOXIRI). Our findings were obtained using second order linear regression and adaptive lasso. RESULTS: The activity of all ODCs was validated on patient-derived organoids (PDO) from cases with either primary or metastatic CRC. The CRC material was molecularly characterized using whole-exome sequencing and RNAseq. In PDO from patients with liver metastases (stage IV) identified as CMS4/CRIS-A, our ODCs consisting of regorafenib [1 mM], vemurafenib [11 mM], palbociclib [1 mM] and lapatinib [0.5 mM] inhibited cell viability up to 88%, which significantly outperforms FOLFOXIRI administered at clinical doses. Furthermore, we identified patient-specific TGMO-based ODCs that outperform the efficacy of the current chemotherapy standard of care, FOLFOXIRI. CONCLUSIONS: Our approach allows the optimization of patient-tailored synergistic multi-drug combinations within a clinically relevant timeframe.

Anti-CD122 antibody restores specific CD8+ T cell response in nonalcoholic steatohepatitis and prevents hepatocellular carcinoma growth.

Nonalcoholic steatohepatitis (NASH) can lead to hepatocellular carcinoma (HCC). Although immunotherapy is used as first-line treatment for advanced HCC, the impact of NASH on anticancer immunity is only partially characterized. We assessed the tumor-specific T cell immune response in the context of NASH. In a mouse model of NASH, we observed an expansion of the CD44+CXCR6+PD-1+CD8+ T cells in the liver. After intra-hepatic injection of RIL-175-LV-OVA-GFP HCC cells, NASH mice had a higher percentage of peripheral OVA-specific CD8+ T cells than control mice, but these cells did not prevent HCC growth. In the tumor, the expression of PD-1 on OVA-specific CD44+CXCR6+CD8+ cells was higher in NASH mice suggesting lowered immune activity. Treating mice with an anti-CD122 antibody, which reduced the number of CXCR6+PD-1+ cells, we restored OVA-specific CD8 activity, and reduced HCC growth compared to untreated NASH mice. Human dataset confirmed that NASH-affected livers, NASH tissues adjacent to HCC and HCC in patients with NASH exhibited gene expression patterns supporting mouse observations. Our findings demonstrate the immune system fails to prevent HCC growth in NASH, primarily linked to a higher representation of CD44+CXCR6+PD-1+CD8+ T cells. Treatment with an anti-CD122 antibody reduces the number of these cells and prevents HCC growth.

Surgical Prehabilitation in Patients with Gastrointestinal Cancers: Impact of Unimodal and Multimodal Programs on Postoperative Outcomes and Prospects for New Therapeutic Strategies-A Systematic Review.

The advantages of prehabilitation in surgical oncology are unclear. This systematic review aims to (1) evaluate the latest evidence of preoperative prehabilitation interventions on postoperative outcomes after gastrointestinal (GI) cancer surgery and (2) discuss new potential therapeutic targets as part of prehabilitation. Randomized controlled trials published between January 2017 and August 2022 were identified through Medline. The population of interest was oncological patients undergoing GI surgery. Trials were considered if they evaluated prehabilitation interventions (nutrition, physical activity, probiotics and symbiotics, fecal microbiota transplantation, and ghrelin receptor agonists), alone or combined, on postoperative outcomes. Out of 1180 records initially identified, 15 studies were retained. Evidence for the benefits of unimodal interventions was limited. Preoperative multimodal programs, including nutrition and physical activity with or without psychological support, showed improvement in postoperative physical performance, muscle strength, and quality of life in patients with esophagogastric and colorectal cancers. However, there was no benefit for postoperative complications, hospital length of stay, hospital readmissions, and mortality. No trial evaluated the impact of fecal microbiota transplantation or oral ghrelin receptor agonists. Further studies are needed to confirm our findings, identify patients who are more likely to benefit from surgical prehabilitation, and harmonize interventions.