Experimental models of high-risk bowel anastomosis in rats: A systematic review.

BACKGROUND: Anastomotic leaks remain one of the most dreaded complications in gastrointestinal surgery causing significant morbidity, that negatively affect the patients' quality of life. Experimental studies play an important role in understanding the pathophysiological background of anastomotic healing and there are still many fields that require further investigation. Knowledge drawn from these studies can lead to interventions or techniques that can reduce the risk of anastomotic leak in patients with high-risk features. Despite the advances in experimental protocols and techniques, designing a high-quality study is still challenging for the investigators as there is a plethora of different models used. AIM: To review current state of the art for experimental protocols in high-risk anastomosis in rats. METHODS: This systematic review was performed according to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. To identify eligible studies, a comprehensive literature search was performed in the electronic databases PubMed (MEDLINE) and Scopus, covering the period from conception until 18 October 2023. RESULTS: From our search strategy 102 studies were included and were categorized based on the mechanism used to create a high-risk anastomosis. Methods of assessing anastomotic healing were extracted and were individually appraised. CONCLUSION: Anastomotic healing studies have evolved over the last decades, but the findings are yet to be translated into human studies. There is a need for high-quality, well-designed studies that will help to the better understanding of the pathophysiology of anastomotic healing and the effects of various interventions.

Near-infrared cholangiography with intragallbladder indocyanine green injection in minimally invasive cholecystectomy.

Laparoscopic cholecystectomy (LC) remains one of the most commonly performed procedures in adult and paediatric populations. Despite the advances made in intraoperative biliary anatomy recognition, iatrogenic bile duct injuries during LC represent a fatal complication and consist an economic burden for healthcare systems. A series of methods have been proposed to prevent bile duct injury, among them the use of indocyanine green (ICG) fluorescence. The most commonly reported method of ICG injection is the intravenous administration, while literature is lacking studies investigating the direct intragallbladder ICG injection. This narrative mini-review aims to assess the potential applications, usefulness, and limitations of intragallbladder ICG fluorescence in LC. Authors screened the available international literature to identify the reports of intragallbladder ICG fluorescence imaging in minimally invasive cholecystectomy, as well as special issues regarding its use. Literature search retrieved four prospective cohort studies, three case-control studies, and one case report. In the three case-control studies selected, intragallbladder near-infrared cholangiography (NIRC) was compared with standard LC under white light, with intravenous administration of ICG for NIRC and with standard intraoperative cholangiography (IOC). In total, 133 patients reported in the literature have been administered intragallbladder ICG administration for biliary mapping during LC. Literature includes several reports of intragallbladder ICG administration, but a standardized technique has not been established yet. Published data suggest that NIRC with intragallbladder ICG injection is a promising method to achieve biliary mapping, overwhelming limitations of IOC including intervention and radiation exposure, as well as the high hepatic parenchyma signal and time interval needed in intravenous ICG fluorescence. Evidence-based guidelines on the role of intragallbladder ICG fluorescence in LC require the assessment of further studies and multicenter data collection into large registries.

The EUropean PErioperative MEdical networking (EUPEMEN) project: recommendations for perioperative care in colorectal surgery. a quality improvement study.

BACKGROUND: Despite consensus supporting enhanced recovery programs, their full implementation in such a context is difficult due to conventional practices within various groups of professionals. The goal of the EUropean PErioperative MEdical Networking (EUPEMEN) project was to bring together the expertise and experience of national clinical professionals who have previously helped deliver major change programs in their countries and to use them to spread enhanced recovery after surgery protocols (ERAS) in Europe. The specific aim of this study is to present and discuss the key points of the proposed recommendations for colorectal surgery. MATERIALS AND METHODS: Five partners from university hospitals in four European countries developed the project as partners. Following a non-systematic review of the literature, the European consensus panel generated a list of recommendations for perioperative care in colorectal surgery. A list of recommendations was formulated and distributed to collaborators at each center to allow modifications or additional statements. These recommendations were then discussed in three consecutive meetings to share uniform ERAS protocols to be disseminated. RESULT: The working group developed (1) the EUPEMEN online platform to offer, free of charge, evidence-based standardized perioperative care protocols, learning activities, and assistance to health professionals interested in enhancing the recovery of their patients; (2) the preparation of the EUPEMEN Multimodal Rehabilitation manuals; (3) the training of the trainers to teach future teachers; and (4) the dissemination of the results in five multiplier events, one for each partner, to promote and disseminate the protocols. CONCLUSION: The EUPEMEN project allowed the sharing of the expertise of many professionals from four different European countries with the objective of training the new generations in the dissemination of ERAS protocols in daily clinical practice through a new learning system. This project was proposed as an additional training tool for all the enhanced recovery program teams.

Biliary Anatomy Visualization and Surgeon Satisfaction Using Standard Cholangiography versus Indocyanine Green Fluorescent Cholangiography during Elective Laparoscopic Cholecystectomy: A Randomized Controlled Trial.

Background: Intraoperative biliary anatomy recognition is crucial for safety during laparoscopic cholecystectomy, since iatrogenic bile duct injuries represent a fatal complication, occurring in up to 0.9% of patients. Indocyanine green fluorescence cholangiography (ICG-FC) is a safe and cost-effective procedure for achieving a critical view of safety and recognizing early biliary injuries. The aim of this study is to compare the perioperative outcomes, usefulness and safety of standard intraoperative cholangiography (IOC) with ICG-FC with intravenous ICG. Methods: Between 1 June 2021 and 31 December 2022, 160 patients undergoing elective LC were randomized into two equal groups: Group A (standard IOC) and group B (ICG-FC with intravenous ICG). Results: No significant difference was found between the two groups regarding demographics, surgery indication or surgery duration. No significant difference was found regarding the visualization of critical biliary structures. However, the surgeon satisfaction and cholangiography duration presented significant differences in favor of ICG-FC. Regarding the inflammatory response, a significant difference between the two groups was found only in postoperative WBC levels. Hepatic and renal function test results were not significantly different between the two groups on the first postoperative day, except for direct bilirubin. No statistically significant difference was noted regarding 30-day postoperative complications, while none of the complications noted included bile duct injury events. Conclusions: ICG-FC presents equivalent results to IOC regarding extrahepatic biliary visualization and postoperative complications. However, more studies need to be performed in order to standardize the optimal dose, timing and mode of administration.

Effect of Intraperitoneal Chemotherapy with Regorafenib on IL-6 and TNF-α Levels and Peritoneal Cytology: Experimental Study in Rats with Colorectal Peritoneal Carcinomatosis.

Cytoreductive surgery (CRS), combined with hyperthermic intraperitoneal chemotherapy, has significantly improved survival outcomes in patients with peritoneal carcinomatosis from colorectal cancer (CRC). Regorafenib is an oral agent administered in patients with refractory metastatic CRC. Our aim was to investigate the outcomes of intraperitoneal administration of regorafenib for intraperitoneal chemotherapy (IPEC) or/and CRS in a rat model of colorectal peritoneal metastases regarding immunology and peritoneal cytology. A total of 24 rats were included. Twenty-eight days after carcinogenesis induction, rats were randomized into following groups: group A: control group; group B: CRS only; group C: IPEC only; and group D: CRS + IPEC. On day 56 after carcinogenesis, euthanasia and laparotomy were performed. Serum levels of interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) as well as peritoneal cytology were investigated. Groups B and D had statistically significant lower mean levels of IL-6 and TNF-α compared to groups A and C, but there was no significant difference between them. Both B and D groups presented a statistically significant difference regarding the rate of negative peritoneal cytology, when compared to the control group, but not to group C. In conclusion, regorafenib-based IPEC, combined with CRS, may constitute a promising tool against peritoneal carcinomatosis by altering the tumor microenvironment.

The Role of Adipose Tissue Mesenchymal Stem Cells in Colonic Anastomosis Healing in Inflammatory Bowel Disease: Experimental Study in Rats.

(1) Background: A surgical operation on an inflamed bowel is, diachronically, a challenge for the surgeon, especially for patients with inflammatory bowel disease. Adipose tissue-derived mesenchymal stromal cells are already in use in clinical settings for their anti-inflammatory properties. The rationale of the current study was to use AdMSCs in high-risk anastomoses to monitor if they attenuate inflammation and prevent anastomotic leak. (2) Methods: a total of 4 groups of rats were subjected to a surgical transection of the large intestine and primary anastomosis. In two groups, DSS 5% was administered for 7 days prior to the procedure, to induce acute intestinal inflammation. After the anastomosis, 5 × 106 autologous AdMSCs or an acellular solution was injected locally. Macroscopic evaluation, bursting pressure, hydroxyproline, and inflammatory cytokine expression were the parameters measured on the 8th post-operative day. (3) Results: Significantly less intra-abdominal complications, higher bursting pressures, and a decrease in pro-inflammatory markers were found in the groups that received AdMSCs. No difference in VEGF expression was observed on the 8th post-operative day. (4) Conclusions: AdMSCs attenuate inflammation in cases of acutely inflamed anastomosis.

The Efficacy of Probiotics, Prebiotics, and Synbiotics in Patients Who Have Undergone Abdominal Operation, in Terms of Bowel Function Post-Operatively: A Network Meta-Analysis.

BACKGROUND: Abdominal operations may lead to post-operative bowel dysfunction, while administration of probiotics, prebiotics and synbiotics may limit its manifestation. Τhe study aimed to assess the efficacy of probiotics, prebiotics and synbiotics in patients who undergone abdominal operation, in terms of bowel function post-operatively. METHODS: PubMed, Scopus, Cochrane Central Register of Controlled Trials (Central), Embase, US Registry of clinical trials, and sources of grey literature were searched. The relative effect sizes were estimated, and we obtained the relative ranking of the interventions using cumulative ranking curves. RESULTS: In total, 30 studies were included in the analysis. For the outcome of post-operative ileus, probiotics was superior to placebo/no intervention (relative risk, RR: 0.38; 95%CI: 0.14-0.98) with the highest SUCRA (surface under the cumulative ranking) value (92.1%). For time to first flatus, probiotics (MD: -0.47; 95%CI: -0.78 to -0.17) and synbiotics (MD: -0.53; 95%CI: -0.96 to -0.09) were superior to placebo/no intervention. For time to first defecation and for post-operative abdominal distension probiotics were superior to placebo/no intervention. For post-operative hospitalization days, synbiotics were superior to placebo/no intervention (MD: -3.07; 95%CI: -4.80 to -1.34). CONCLUSIONS: Administration of probiotics in patients who had undergone abdominal surgery reduced the prevalence of post-operative ileus, time to first flatus, time to first defecation, and prevalence of post-operative abdominal distension. Synbiotics reduce time to first flatus and post-operative hospitalization days.

Laparoscopic para-aortic lymphadenectomy for metastatic colon cancer in a patient with left-sided inferior vena cava: a case report.

Transposition of inferior vena cava, or, left-sided inferior vena cava (LS-IVC) is a rare clinical entity, in which the inferior vena cava ascends along the left side of the abdominal aorta. Literature contains mainly clinical case reports. Although it is usually not associated with clinical symptomatology, this anomaly should be detected during preoperative planning to avoid iatrogenic injuries intraoperatively. We present a case of left-sided inferior vena cava encountered during laparoscopic lymphadenectomy in a 45-year-old man with previous laparoscopic hemicolectomy due to colon adenocarcinoma. Preoperative CT abdomen revealed the left-sided location of infrarenal IVC and laparoscopic trans-peritoneal aortic lymphadenectomy was decided. Intraoperatively, transposition of inferior vena cava was confirmed in accordance with the CT findings. Resection of lymph node block was conducted with no complications and with minimal blood loss. The postoperative course was uneventful, and the patient was discharged from the hospital the day following surgery. In conclusion, transposition of the inferior vena cava, although rare, constitutes an anatomical variant that should be identified preoperatively to decrease intraoperative risks. Several anatomical variants have been associated with left-sided inferior vena cava.

The feasibility and effect of intraperitoneal administration of regorafenib on peritoneal carcinomatosis from colorectal cancer in the rat.

AIM: Our goal was to investigate the potential use and efficacy of regorafenib for IPEC in an animal model of colorectal derived peritoneal metastases. Twenty four male rats were included. Carcinogenesis was induced in all rats through intraperitoneal injection of cancer. MATERIAL AND METHODS: Cells at T0. At T1(Day 28) they were randomly allocated 1:1:1:1 into 4 groups and underwent median laparotomy and the corresponding intervention. Specifically, Group A: no other intervention; Group B: cytoreductive surgery; Group C: intraperitoneal chemotherapy with regorafenib; and Group D: cytoreductive surgery and intraperitoneal chemotherapy with regorafenib. At T2 (Day 56) rats were euthanized and laparotomy was performed for further investigation. The primary outcome was the experimental Peritoneal Cancer Index (ePCI) at T2. Secondary outcomes include relative change of body weight between T1 and T2, weight of the ascites, anastomotic leak/peritonitis and death. RESULTS: The ePCI was significantly lower in Group D as opposed to all other groups. Comparing Group C versus Group A we found a trend towards lesser tumor progression, but no significant difference. Growth of rats in Group D was significantly least affected compared to all other groups. Animals undergoing CRS in Group B developed less ascites than Group A and C. Less ascites was found in Group D compared to Group A and C. CONCLUSIONS: Intraperitoneal chemotherapy with regorafenib combined with cytoreductive surgery may impair metastases' progression. KEY WORDS: Regorafenib, Chemotherapy, Cytoreductive surgery, Colorectal cancer, Intraperitoneal injection.

Effect of N-acetyl-L-cysteine on inflammation after intraperitoneal mesh placement in a potentially contaminated environment: An experimental study in the rat.

BACKGROUND: The use of prosthetic meshes in abdominal wall reconstruction is a well-established approach; however, in certain cases where a bowel resection coexists its application is disputed. Any underlying inflammatory process may augment adhesion formation which is a major postoperative complication. In this animal study, our aim was to investigate the effect of N-acetyl-l-cysteine (NAC) on adhesion formation and the expression of inflammatory markers when a mesh was used in a clean or a potentially contaminated environment. METHODS: Sixty male Wistar rats were randomly and equally allocated in 3 groups: A, B and C. Animals in all groups underwent laparotomy, a prosthetic mesh was placed and chemoprophylaxis with ciprofloxacin was administered. In groups B and C an enterectomy was also performed. NAC was injected intraperitoneally in group C. Adhesion formation, IL-1a, IL-6, TNF-a and histological data including fibrosis, neutrophils' infiltration and neovascularization were assessed. Mesh samples were sent for cultivation. RESULTS: Adhesion formation was significantly less and inflammation markers were also lower in group C compared to group B (p<0.05). Histological findings were significant for greater fibrosis, neutrophils' infiltration and neovascularization in group B compared to both group A and C. Regarding mesh cultures, more specimens were tested positive in group B (p <0.05). Outcomes between group A and C did not differ. CONCLUSION: NAC effectively ameliorated adhesion formation and inflammation in a potentially septic environment where a prosthetic mesh was placed.

Case Report: A Virilizing Adrenal Oncocytoma.

A 64-year-old female was admitted to our clinic with a 9-cm-sized adrenal mass. The patient's main symptom was hirsutism, which included thinning scalp hair and excessive hair growth over her torso and arms. Upon investigation, elevated values of testosterone, androsterone D4, and DHEA-S were found. Contrast-enhanced abdominal CT and MRI scans revealed a heterogenous large mass (diameter 9 × 8.5 cm) with focal calcifications, necrotic areas, and a clear distinction from the adjacent structures. The patient underwent a right adrenalectomy. The histological examination of the tumor revealed a borderline adrenocortical oncocytoma. The patient had an uncomplicated postoperative course and was discharged on postoperative day 8. Similar cases reported in the literature are also being reviewed in this case report.

Giant Adrenocortical Carcinoma: A Case Report and Review of the Relevant Literature.

BACKGROUND Adrenocortical carcinomas are rare and aggressive tumors often diagnosed as incidentalomas. The malignancy can present with abnormal hormone secretion or the tumor may be non-functioning and present as a palpable mass causing discomfort. Here, we present a case of an adrenal cortical carcinoma originally identified as an incidentaloma. CASE REPORT A 63-year-old woman presented with abdominal pain and discomfort. A large abdominal mass, occupying the left upper and lower quadrant, was palpated. Imaging revealed a mass occupying the left abdomen between the stomach and the spleen, applying pressure on the pylorus, duodenum, splenic vessels, and pancreas. The mass size was 21.2×13×14.6 cm. Hormonal investigations were normal. Surgical exploration was performed, and the tumor was excised. Pathological analysis revealed an adrenocortical carcinoma and the patient underwent adjuvant chemotherapy. Twelve months later, the carcinoma recurred. The patient underwent a second operation in which the recurrent mass was excised along with the tail of the pancreas and a small part of the left lobe of the liver. The postoperative period was uneventful, and the patient was discharged home on the 7th postoperative day. No further adjuvant therapy was applied. The patient remains disease-free 18 months after the reoperation. CONCLUSIONS Giant adrenocortical carcinomas, although rare, pose a challenge to the surgical team both diagnostically and therapeutically. Surgical excision with the appropriate oncologic support can guarantee excellent outcomes.

Metalloproteinase expression after desflurane preconditioning in hepatectomies: A randomized clinical trial.

BACKGROUND: Hepatectomy with inflow occlusion results in ischemia-reperfusion injury; however, pharmacological preconditioning can prevent such injury and optimize the postoperative recovery of hepatectomized patients. The normal inflammatory response after a hepatectomy involves increased expression of metalloproteinases, which may signal pathologic hepatic tissue reformation. AIM: To investigate the effect of desflurane preconditioning on these inflammatory indices in patients with inflow occlusion undergoing hepatectomy. METHODS: This is a single-center, prospective, randomized controlled trial conducted at the 4th Department of Surgery of the Medical School of Aristotle University of Thessaloniki, between August 2016 and December 2017. Forty-six patients were randomized to either the desflurane treatment group for pharmacological preconditioning (by replacement of propofol with desflurane, administered 30 min before induction of ischemia) or the control group for standard intravenous propofol. The primary endpoint of expression levels of matrix metalloproteinases and their inhibitors was determined preoperatively and at 30 min posthepatic reperfusion. The secondary endpoints of neutrophil infiltration, coagulation profile, activity of antithrombin III (AT III), protein C (PC), protein S and biochemical markers of liver function were determined for 5 d postoperatively and compared between the groups. RESULTS: The desflurane treatment group showed significantly increased levels of tissue inhibitor of metalloproteinases 1 and 2, significantly decreased levels of matrix metalloproteinases 2 and 9, decreased neutrophil infiltration, and less profound changes in the coagulation profile.  During the 5-d postoperative period, all patients showed significantly decreased activity of AT III, PC and protein S (vs baseline values, P < 0.05). The activity of AT III and PC differed significantly between the two groups from postoperative day 1 to postoperative day 5 (P < 0.05), showing a moderate drop in activity of AT III and PC in the desflurane treatment group and a dramatic drop in the control group. Compared to the control group, the desflurane treatment group also had significantly lower international normalized ratio values on all postoperative days (P < 0.005) and lower serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase values on postoperative days 2 and 3 (P < 0.05).   Total length of stay was significantly less in the desflurane group (P = 0.009). CONCLUSION: Desflurane preconditioning can lessen the inflammatory response related to ischemia-reperfusion injury and may shorten length of hospitalization.