Evidence for platelet-derived transforming growth factor ß1 as an early inducer of liver regeneration after hepatectomy in mice.

Platelets play a crucial role in tissue regeneration, and their involvement in liver regeneration is well-established. However, the specific contribution of platelet-derived Transforming Growth Factor Beta 1 (TGFß1) to liver regeneration remains unexplored. This study investigated the role of platelet-derived TGFß1 in initiating liver regeneration following 2/3 liver resection. Using platelet-specific TGFß1 knockout (Plt.TGFß1 KO) mice and wild-type littermates (Plt.TGFß1 WT) as controls, the study assessed circulating levels and hepatic gene expression of TGFß1, Platelet Factor 4 (PF4), and Thrombopoietin (TPO) at early time points post-hepatectomy (post-PHx). Hepatocyte proliferation was quantified through Ki67 staining and PCNA expression in total liver lysates at various intervals, and phosphohistone-H3 (PHH3) staining was employed to mark mitotic cells. Circulating levels of hepatic mitogens, Hepatocyte Growth Factor (HGF), and Interleukin-6 (IL6) were also assessed. Results revealed that platelet-TGFß1 deficiency significantly reduced total plasma TGFß1 levels at 5 h post-PHx in Plt.TGFß1 KO mice compared to controls. While circulating PF4 levels, liver platelet recruitment and activation appeared normal at early time points, Plt.TGFß1 KO mice showed more stable circulating platelet numbers with higher numbers at 48 h post-PHx. Notably, hepatocyte proliferation was significantly reduced in Plt.TGFß1 KO mice. The results show that a lack of TGFß1 in platelets leads to an unbalanced expression of IL6 in the liver and to strongly increased HGF levels 48 h after liver resection, and yet liver regeneration remains reduced. The study identifies platelet-TGFß1 as a regulator of hepatocyte proliferation and platelet homeostasis in the early stages of liver regeneration.

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.

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.

Spontaneous lesser omental herniation resolved by laparoscopic surgery: case report and systematic literature review.

BACKGROUND: Despite its extremely low incidence, intra-abdominal herniation through the lesser omentum is associated with a high mortality rate and must be recognized early and treated urgently. To overcome a lack of data on the management of this condition, we collected and reviewed all the reported cases of operated lesser omental hernia and presented the case of a patient treated by laparoscopy for an isolated lesser omental hernia. METHODS: According to PRISMA guidelines and using PubMed, Cochrane Library, and Web of Science, a systematic literature review of cases of lesser omental hernia treated by surgery was performed on February 12, 2023. RESULTS: Of 482 articles, 30 were included for analysis and only 9 articles presented an isolated hernia through the lesser omentum. Among these, 4 patients were female and the median age was 38. Upper abdominal pain and vomiting were reported in 7 out of 9 patients. The small bowel was responsible for 78% (7/9) of all lesser omental herniations. All of them were treated by laparotomy. In addition, we describe the case of a 65-year-old woman without prior surgical history who was treated by laparoscopy for a spontaneous closed loop hernia through the lesser omentum without any other associated hernias. CONCLUSION: Mostly associated with prior surgery or trauma, this type of herniation could sometimes occur spontaneously without any sign of peritonitis. Due to the high mortality rate, internal abdominal hernias should always be ruled out with a CT scan in front of patients presenting with persisting acute abdominal pain and no alternative diagnosis.

Isolation and Characterization of Stem Cells from the Anal Canal Transition Zone in Pigs.

BACKGROUND: Utilization of autologous stem cells has been proposed for the treatment of anal incontinence despite a lack of understanding of their mechanism of action and of the physiological healing process of anal sphincters after injury. AIMS: We aim to develop a technique allowing isolation and further study of local mesenchymal stem cells, directly from anal canal transition zone in pig. METHODS: Anal canal was resected "en bloc" from two young pigs and further microdissected. The anal canal transition zone was washed and digested with 0.1% type I collagenase for 45 min at 37 °C. The isolated cells were plated on dishes in mesenchymal stem cell medium and trypsinized when confluent. Cells were further used for flow cytometry analysis and differentiation assays. RESULTS: The anal canal transition zone localization was confirmed with H&E staining. Following culture, cells exhibited a typical "fibroblast-like" morphology typical of stem cells. Isolated cells were positive for CD90 and CD44 but negative for CD14, CD34, CD45, CD105, CD106, and SLA-DR. Following incubation with specific differentiation medium, isolated cells differentiated into adipocytes, osteoblasts, and chondrocytes, confirming in vitro multipotency. CONCLUSIONS: Herein, we report for the first time the presence of mesenchymal stem cells in the anal canal transition zone in pigs and the feasibility of their isolation. This preliminary study opens the path to the isolation of human anal canal transition zone mesenchymal stem cells that might be used to study sphincters healing and to treat anal incontinence.

Multipotent mesenchymal stromal cells derived from porcine exocrine pancreas improve insulin secretion from juvenile porcine islet cell clusters.

Neonatal and juvenile porcine islet cell clusters (ICC) present an unlimited source for islet xenotransplantation to treat type 1 diabetes patients. We isolated ICC from pancreata of 14 days old juvenile piglets and characterized their maturation by immunofluorescence and insulin secretion assays. Multipotent mesenchymal stromal cells derived from exocrine tissue of same pancreata (pMSC) were characterized for their differentiation potential and ability to sustain ICC insulin secretion in vitro and in vivo. Isolation of ICC resulted in 142 ± 50 × 103 IEQ per pancreas. Immunofluorescence staining revealed increasing presence of insulin-positive beta cells between day 9 and 21 in culture and insulin content per 500IEC of ICC increased progressively over time from 1178.4 ± 450 µg/L to 4479.7 ± 1954.2 µg/L from day 7 to 14, P < .001. Highest glucose-induced insulin secretion by ICC was obtained at day 7 of culture and reached a fold increase of 2.9 ± 0.4 compared to basal. Expansion of adherent cells from the pig exocrine tissue resulted in a homogenous CD90+ , CD34- , and CD45- fibroblast-like cell population and differentiation into adipocytes and chondrocytes demonstrated their multipotency. Insulin release from ICC was increased in the presence of pMSC and dependent on cell-cell contact (glucose-induced fold increase: ICC alone: 1.6 ± 0.2; ICC + pMSC + contact: 3.2 ± 0.5, P = .0057; ICC + pMSC no-contact: 1.9 ± 0.3; theophylline stimulation: alone: 5.4 ± 0.7; pMSC + contact: 8.4 ± 0.9, P = .013; pMSC no-contact: 5.2 ± 0.7). After transplantation of encapsulated ICC using Ca2+ -alginate (alg) microcapsules into streptozotocin-induced diabetic and immunocompetent mice, transient normalization of glycemia was obtained up to day 7 post-transplant, whereas ICC co-encapsulated with pMSC did not improve glycemia and showed increased pericapsular fibrosis. We conclude that pMSC derived from juvenile porcine exocrine pancreas improves insulin secretion of ICC by direct cell-cell contact. For transplantation purposes, the use of pMSC to support beta-cell function will depend on the development of new anti-fibrotic polymers and/or on genetically modified pigs with lower immunogenicity.

Prevalence of Metastatic Lateral Lymph Nodes in Asian Patients with Lateral Lymph Node Dissection for Rectal Cancer: A Meta-analysis.

IMPORTANCE: Rectal cancers occupy the eighth position worldwide for new cases and deaths for both men and women. These cancers have a high tendency to form metastases in the mesorectum but also in the lateral lymph nodes. The therapeutic approach for the involved lateral lymph nodes remains controversial. OBJECTIVE: We performed a systematic review and meta-analysis to assess the prevalence of metastatic lateral lymph nodes in patients with lateral lymph node dissection (LLND) for rectal cancer, which seems to be a fundamental and necessary criterion to discuss any possible indications for LLND. METHODS: Data sources-study selection-data extraction and synthesis-main outcome and measures. We searched MEDLINE, EMBASE and COCHRANE from November 1, 2018, to November 19, 2018, for studies reporting the presence of metastatic lateral lymph nodes (iliac, obturator and middle sacral nodes) among patients undergoing rectal surgery with LLND. Pooled prevalence values were obtained by random effects models, and the robustness was tested by leave-one-out sensitivity analyses. Heterogeneity was assessed using the Q-test, quantified based on the I2 value and explored by subgroup analyses. RESULTS: Our final analysis included 31 studies from Asian countries, comprising 7599 patients. The pooled prevalence of metastatic lateral lymph nodes was 17.3% (95% CI: 14.6-20.5). The inter-study variability (heterogeneity) was high (I2 = 89%). The pooled prevalence was, however, robust and varied between 16.6% and 17.9% according to leave-one-out sensitivity analysis. The pooled prevalence of metastatic lymph nodes was not significantly different when pooling only studies including patients who received neoadjuvant treatment or those without neoadjuvant treatment (p = 0.44). Meta-regression showed that the pooled prevalence was associated with the sample size of studies (p < 0.05), as the prevalence decreased when the sample size increased. CONCLUSION: The pooled prevalence of metastatic lateral lymph nodes was 17.3% among patients who underwent rectal surgery with LLND in Asian countries. Further studies are necessary to determine whether this finding could impact the therapeutic strategy (total mesorectal excision with LLND versus total mesorectal excision with neoadjuvant radiochemotherapy).

Sacro-coxxygial hygiene, a key factor in the outcome of pilonidal sinus surgical treatment?

BACKGROUND: Surgical wound infection contributes to prolonged recovery time after pilonidal sinus excision. As a standard procedure after surgery, we recommend our patients to perform water irrigations in the intergluteal cleft 4 to 6 times a day during the post-operative period. Our hypothesis is that this should reduce healing time and complication rates. The aim of this study was to measure the importance of sacro coccygeal hygiene in the management of pilonidal sinus disease. METHODS: We retrospectively collected data after surgical management of pilonidal sinus (sinusectomy procedures) in our division over a 10-year period. Patients were divided into three groups according to their local hygiene during postoperative follow-up and scored one (G1: good hygiene) to three (G3: poor hygiene). Primary outcome was complication rates. Secondary endpoints were, healing time, follow-up, time off work, and recurrence rate. RESULTS: In G1 (N = 112), complication rate was 3.6%. In G2 (N = 109), it was 5.5%, whereas in G3 (N = 71), it reached 7.03%. However, there were no statistically significant differences between hygiene groups regarding complication rates in both univariate and multivariable analysis. Regarding secondary outcomes, there were significant differences between hygiene groups concerning median follow-up (p = 0.0001) and median time off work (p = 0.0127). CONCLUSION: Good hygiene of wound is essential for optimal, rapid healing without complications. The importance of this report is to show that thanks to our hygiene follow-up strategy with frequent perineal irrigations and regular follow-up checks, patients with at a first glance "unclean local conditions", reached similar complications, median healing time and recurrences rates to patients with medium and good wound hygiene level.

Risk of Colorectal Cancer in Patients With Acute Diverticulitis: A Systematic Review and Meta-analysis of Observational Studies.

BACKGROUND & AIMS: We performed a systematic review and meta-analysis to assess the prevalence of colorectal cancer in patients with acute diverticulitis. METHODS: We searched MEDLINE from inception through November 2nd, 2017 for studies reporting the prevalence of colorectal cancer in patients with diverticulitis, identified based on the protocol CRD42017083272. This systematic review was conducted in accordance to the MOOSE guidelines. Pooled prevalence values were obtained by random effects models and robustness was tested by leave-one out sensitivity analyses. Heterogeneity was assessed using the Q-test and quantified based on I2 value. The critical appraisal of included studies was performed using the Newcastle-Ottawa scale. RESULTS: Our final analysis included 31 studies, comprising 50,445 patients. The pooled prevalence of colorectal cancer was 1.9% (95% CI, 1.5%-2.3%). Patients with complicated diverticulitis had a significantly higher risk for colorectal cancer (prevalence, 7.9%; 95% CI, 3.9%-15.3%) than patients with uncomplicated diverticulitis (prevalence, 1.3%; 95% CI, 0.1%-2%), corresponding to a pooled prevalence ratio of 6.7 (95% CI, 2.5-18.3). Subgroup analyses did not find significant difference in prevalence when separately pooling studies according to ranking on the Newcastle-Ottawa scale, geographical location or length of follow-up. Meta-regression did not find any association between age and colorectal cancer. Among patients who underwent endoscopy, the pooled prevalence of polyps was 22.7% (95% CI, 19.6%-26.0%), of advanced adenomas was 4.4% (95% CI, 3.4%-5.8%), of adenomas was 14.2% (95% CI, 11.7%-17.1%), and of hyperplastic polyps was 9.2% (95% CI, 7.6%-11.2%). CONCLUSION: In a meta-analysis of observational studies of patients with acute diverticulitis, we found the pooled prevalence of colorectal cancer to be 1.9%. The risk of colorectal cancer was significantly higher in patients with complicated diverticulitis than in patients with uncomplicated diverticulitis.

Extracellular vesicles: Future diagnostic and therapeutic tools for liver disease and regeneration.

Extracellular vesicles are membrane fragments that can be produced by all cell types. Interactions between extracellular vesicles and various liver cells constitute an emerging field in hepatology and recent evidences have established a role for extracellular vesicles in various liver diseases and physiological processes. Extracellular vesicles originating from liver cells are implicated in intercellular communication and fluctuations of specific circulating extracellular vesicles could constitute new diagnostic tools. In contrast, extracellular vesicles derived from progenitor cells interact with hepatocytes or non-parenchymal cells, thereby protecting the liver from various injuries and promoting liver regeneration. Our review focuses on recent developments investigating the role of various types of extracellular vesicles in acute and chronic liver diseases as well as their potential use as biomarkers and therapeutic tools.