Probiotic Supplementation Attenuates Chemotherapy-Induced Intestinal Mucositis in an Experimental Colorectal Cancer Liver Metastasis Rat Model.

The use of chemotherapeutic agents is of paramount importance when treating colorectal cancer (CRC). Unfortunately, one of the most frequent chemotherapy (CTx) side effects is intestinal mucositis (IM), which may present with several clinical symptoms such as nausea, bloating, vomiting, pain, and diarrhea and even can result in life-threatening complications. There is a focused scientific effort towards developing new therapies to prevent and treat IM. The aim of this study was to assess the outcomes of probiotic supplementation on CTx-induced IM in a CRC liver metastasis rat model. Six-week-old male Wistar rats received either a multispecies probiotic or placebo mixture. On the 28th experiment day, rats received FOLFOX CTx, and afterwards, the severity of diarrhea was evaluated twice daily. Stool samples were collected for further microbiome analysis. Additionally, immunohistochemical stainings of ileum and colon samples with were performed with MPO, Ki67, and Caspase-3 antibodies. Probiotic supplementation alleviates the severity and length of CTx-induced diarrhea. Additionally, probiotics significantly reduced FOLFOX-induced weight and blood albumin loss. Furthermore, probiotic supplementation mitigated CTx-induced histological changes in the gut and promoted intestinal cell regeneration. This study shows that multispecies probiotic supplementation attenuates FOLFOX-induced IM symptoms by inhibiting apoptosis and promoting intestinal cell proliferation.

Evaluation, management and future perspectives of anal pruritus: a narrative review.

PURPOSE: The without a time limitation. Most recent search was performed on 1st June 2022. RESULTS: Thorough history and physical examination are very important in view of multiple possible causes of anal pruritus. Most of the focus during examination is drawn on to the perianal region. A digital rectal examination and an anoscopy are essential. It is necessary aim of this narrative review is to overview the classification, diagnostics, possible treatment options and future perspective of anal pruritus. METHODS: The search was performed by two authors (AD and MJ) independently in the following electronic databases: PubMed, EMBASE, Web of Science, Cochrane Library, CENTRAL and the Allied and Complementary Medicine Databases (AMED). Search was restricted to English language only to avoid moisture and the use of soaps in the perianal region. Furthermore, the patient should avoid certain foods and increase the intake of fiber. If the symptoms do not resolve, topical steroids, capsaicin (0.006%) and tacrolimus (0.1%) ointments may be used. For intractable cases, intradermal methylene blue injection might give a long-lasting symptom relief. CONCLUSION: Anal pruritus is a long-term deteriorating quality of life issue. Most of the time it is a symptom with a difficult diagnosis. Thorough history and examination should be performed for the best possible treatment.

Experimental Static Cold Storage of the Rat Uterus: Protective Effects of Relaxin- or Erythropoietin-Supplemented HTK-N Solutions.

Uterus transplantation (UTx) is the only treatment method for women with absolute uterine infertility. Currently, the number of grafts retrieved from deceased donors is increasing; hence, prolonged cold ischemia time is inevitable. Thus, this study was designed to assess the effect of the novel relaxin (RLN)- or erythropoietin (EPO)-supplemented Custodiol-N (HTK-N) solutions in an experimental uterus static cold storage (SCS) model. A total of 15 Sprague Dawley rats were used. Uterus horns were randomly assigned into three groups (n = 10/group). SCS was performed by keeping samples at 4 °C in HTK-N solution without or with different additives: 10 IU/mL EPO or 20 nM RLN. Tissue samples were taken after 8 and 24 h of preservation. Uterine tissue histology, and biochemical and immunohistochemical markers were analyzed. No significant differences in SCS-induced tissue damage were observed between groups after 8 h of preservation. Uterine tissue histology, MDA, SOD levels and the TUNEL-positive cell number showed severe damage in HTK-N without additives after 24 h of preservation. This damage was significantly attenuated by adding RLN to the preservation solution. EPO showed no favorable effect. Our study shows that RLN as an additive to an HTK-N solution can serve as an effective uterine tissue preservative in the uterus SCS setting.

Machine Perfusion in Liver Transplantation: A Systematic Review and Meta-Analysis.

Background: Liver transplantation (LTx) is the only treatment option for patients with end-stage liver disease. Novel organ preservation techniques such as hypothermic machine perfusion (HMP) or normothermic machine perfusion (NMP) are under investigation in order to improve organ quality from extended criteria donors and donors after circulatory death. The aim of this study was to systematically review the literature reporting LTx outcomes using NMP or HMP compared to static cold storage (SCS). Methods: The following data were retrieved: graft primary nonfunction rate, early allograft dysfunction (EAD) rate, biliary complication rate, and 12-month graft and patient survival. A total of 15 studies were included (6 NMP and 9 HMP studies), and meta-analysis was performed only for HMP studies because NMP had considerable differences. Results: The systematic review showed the potential of NMP to reduce graft injury and lower the liver graft discard rate. The performed quantitative analyses showed that the use of HMP reduces the rate of EAD (odds ratio [OR] 0.51; 95% confidence interval [CI] 0.34-0.76; p = 0.001; I 2 = 0%) and non-anastomotic biliary strictures (OR 0.34; 95% CI 0.17-0.67; p = 0.002; I 2 = 0%) compared to SCS. Conclusion: Our systematic review and meta-analysis revealed that the use of HMP reduces the rate of EAD and non-anastomotic biliary strictures compared to SCS.

Probiotic Supplementation Suppresses Tumor Growth in an Experimental Colorectal Cancer Liver Metastasis Model.

Colorectal cancer (CRC) ranks third in incidence and second in mortality of all cancers worldwide. At the time of primary diagnosis, around 20% of patients already have metastatic CRC and only around 20% are candidates for radical resection. Thus, most of the patients have to undergo chemotherapy (CTx). Due to chemoresistance and side effects, novel treatment additives are crucial for controlling the disease and prolonging patient survival. The aim of this study was to evaluate probiotic supplementation and its antitumorigenic effects in an experimental CRC liver metastasis model. Six-week-old male Wistar rats received either a multispecies probiotic (1.2 × 109 CFU/daily) or placebo mixture. On day 14 of the experiment, rat CRC cells (CC531) were implanted under the liver capsule later treated by FOLFOX CTx. Change in tumor volume was measured by performing micro computed tomography (micro-CT) scanning on experimental days 28 and 34. Additionally, immunohistochemical staining with anti-MPO, anti-Ki67, and anti-CD31 were performed. Tumor apoptosis was evaluated using TUNEL staining. Micro-CT image analysis indicates that probiotic supplementation significantly inhibits tumor growth. No synergistic effects between probiotic supplementation and FOLFOX CTx was observed. Reduced tumor volume was achieved by inhibiting angiogenesis, as tumor microvascular density was significantly lower in rats receiving probiotic supplementation. This study shows that a multispecies probiotic mixture significantly reduces angiogenesis and inhibits CRC liver metastasis growth in an experimental rat model.

Relaxin and Erythropoietin Significantly Reduce Uterine Tissue Damage during Experimental Ischemia-Reperfusion Injury.

Successful uterus transplantation, a potential treatment method for women suffering from absolute uterine infertility, is negatively affected by ischemia-reperfusion injury (IRI). The aim of this study is to investigate the protective effect of relaxin (RLX) or/and erythropoietin (EPO) on experimental uterus IRI. Eighty rats, randomly assigned into eight groups (n = 10/group), were pretreated with either saline, 5 µg/kg human relaxin-2, 4000 IU/kg recombinant human erythropoietin or their combination. Ischemia was achieved by clamping the aorta and ovarian arteries for 60 min, following 120 min of reperfusion and tissue sampling. For sham animals, clamping was omitted during surgery. There were no differences in tissue histological score, malondialdehyde (MDA) and superoxide dismutase (SOD) levels, myeloperoxidase (MPO) and TUNEL-positive cell count between all sham-operated rats. Pretreatment with RLX preserved normal tissue morphology, reduced MDA levels, MPO and TUNEL-positive cell count, preserved SOD activity and upregulated NICD and HES1 gene expression when compared to the control group. Pretreatment with EPO reduced MDA levels. In conclusion, pretreatment with RLX, EPO or a combination of both EPO and RLX significantly alleviates uterine tissue damage caused by IRI.

Bowel Rest with Total Parenteral Nutrition as an Alternative to Diverting Ileostomy in High-Risk Colorectal Anastomosis: A Pilot Study.

Anastomotic leakage remains the most feared complication in colorectal surgery. Various intraoperative tests evaluate bowel perfusion and mechanical integrity of the colorectal anastomosis. These tests reduce the risk of postoperative anastomotic leakage; however, the incidence remains high. Diverting loop ileostomy mitigates the damage if anastomotic leakage occurs. Nevertheless, ileostomy has a significant rate of complications, reducing patients' quality of life, and requiring an additional operation. We evaluated six consecutive cases where bowel rest with total parenteral nutrition was used instead of diverting loop ileostomy. All colorectal anastomoses were at high risk of postoperative anastomotic leakage. Total parenteral nutrition was administered for the first seven days postoperatively. There were no serious complications during the recovery period, and no clinical postoperative anastomotic leakage was detected. All patients tolerated total parenteral nutrition. Bowel rest with total parenteral nutrition may be a feasible option in high-risk left-sided colorectal anastomosis and a possible alternative to a preventive loop ileostomy. Further studies are necessary to evaluate it on a larger scale.

Preventing hemorrhoids during pregnancy: a multicenter, randomized clinical trial.

BACKGROUND: To compare specific dietary and behavioral recommendations for hemorrhoids prevention during pregnancy. METHODS: This was a randomized, single-blind, multicenter trial conducted in three different clinical centers. Patients were randomly allocated into two groups in a ratio of 1:1. Intervention consisted of specific dietary and behavioral counseling. The primary outcome of this study was the rate of hemorrhoids at the time of discharge from the obstetrics unit. Categorical variables were compared by the Chi-Squared or Fisher exact tests, as appropriate. Continuous variables were compared using either the Student's t-test or the Mann-Whitney U test. Binary logistic regression model was used to identify independent predictors of hemorrhoids after delivery. This analysis was performed on factors with a p-value < 0.10 in univariate analysis. Statistical analysis was performed using IBM SPSS 23.0 and GraphPad Prism 9 software. A P-value of less than 0.05 was considered significant for all tests. RESULTS: We observed a significantly lower hemorrhoids rate in the intervention group at the time of discharge from the obstetrics unit after delivery (intention-to-treat (ITT) (the relative risk (RR) 0.38; 95% the confidence interval (CI) 0.24-0.59; p < 0.001) per-protocol (PP) (RR 0.42; 95% CI 0.27-0.64; p < 0.001). There was no significant difference in spontaneous miscarriage rate between the groups for both ITT and PP analysis. Additional binary logistic regression analysis revealed that the intervention applied in this study was the only protective factor. Both, the history of hemorrhoids before pregnancy and the increase of newborn height was associated with a higher risk of hemorrhoids. CONCLUSIONS: Our suggested intervention, aimed to modify dietary and behavioral habits, significantly reduces the rate of hemorrhoids after pregnancy and can be safely recommended to pregnant women. TRIAL REGISTRATION: Date of registration: 2016-05-09; Date of initial patient enrollment: 2016-06-02; Trial registration number: 158200-16-843-357; Trial registration site URL: https://www.mf.vu.lt/mokslas/vilniaus-regioninis-biomedicininiu-39tyrimu-etikos-komitetas#isduoti40vrbtek-leidimai .

Ischemic Preconditioning for Liver Transplantation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: In recent decades, liver transplantation (LTx) has increased the survival and quality of life of patients with end-stage organ failure. Unfortunately, LTx is limited due to the shortage of donors. A lot of effort is put into finding new ways to reduce ischemia-reperfusion injury (IRI) in liver grafts to increase the number of suitable organs procured from expanded-criteria donors (ECD). The aim of this study was to systematically review the literature reporting LTx outcomes when using ischemic preconditioning (IPC) or remote ischemic preconditioning (RIPC) to reduce IRI in liver grafts. METHODS: A literature search was performed in the MEDLINE, Web of Science, and EMBASE databases. The following combination was used: "Liver" OR "Liver Transplantation" AND "Ischemic preconditioning" OR "occlusion" OR "clamping" OR "Pringle." The following outcome data were retrieved: the rates of graft primary nonfunction (PNF), retransplantation, graft loss, and mortality; stay in hospital and the intensive care unit; and postoperative serum liver damage parameters. RESULTS: The initial search retrieved 4,522 potentially relevant studies. After evaluating 17 full-text articles, a total of 9 randomized controlled trials (RCTs) were included (7 IPC and 2 RIPC studies) in the qualitative synthesis; the meta-analysis was only performed on the data from the IPC studies. RIPC studies had considerable methodological differences. The meta-analysis revealed the beneficial effect of IPC when comparing postoperative aspartate aminotransferase (AST) corresponding to a statistically lower mortality rate in the IPC group (odds ratio [OR] 0.51; 95% confidence interval [CI] 0.27-0.98; p = 0.04). CONCLUSION: IPC lowers postoperative AST levels and reduces the mortality rate; however, data on the benefits of RIPC are lacking.

Local Perianal Anesthetic Infiltration Is Safe and Effective for Anorectal Surgery.

Background: General or regional anesthesia is predominantly used for anorectal surgery, however in the recent years more attention was drawn in the use of local anesthesia for anorectal surgery. In this study we present the technique and results of the use of local perianal anesthetic infiltration for minor anorectal operations. Methods: In this cohort study patients undergoing surgery for hemorrhoids, anal fissures and low anal fistulas were included. Posterior perineal block was induced with a mixture containing 0.125% bupivacaine and 0.5% lidocaine. All patients were followed up at 30 days either by a post-operative visit or a telephone call and all post-operative complications over the post-operative 30-day period were registered. Results: One thousand and twenty-six consecutive patients were included in our study. For all patients' intraoperative analgesia was achieved after performing perianal anesthetic infiltration and no additional support from the anesthesia team was necessary in any of case. Complications were observed in 14 (1.4%). Urinary retention occurred in 5 (0.5%) cases. Six cases of bleeding occurred after hemorrhoidectomy (0.6%) and 1 (0.1%) after lateral internal sphincterotomy. Perianal abscess developed for two patients (0.2%). Conclusions: Local anesthesia using posterior perineal block technique is safe and effective for intraoperative analgesia in anorectal surgery, saving a substantial operation cost by avoiding the involvement of an anesthesia team and resulting in minimal incidence of urinary retention and other complications.

Intraoperative testing of colorectal anastomosis and the incidence of anastomotic leak: A meta-analysis.

BACKGROUND: AL remains one of the most threatening complications in colorectal surgery. Significant efforts are put to understand the pathophysiological mechanisms involved in the development of leakage and to create the strategies to prevent it. We aimed to determine whether intraoperative testing of mechanical integrity and perfusion of colorectal anastomosis could reduce the incidence of AL. METHODS: A systematic review and meta-analysis of papers published before November 2019 on PubMed, Scopus, Web of Science, and Cochrane Library databases and comparing intraoperative testing of the colorectal anastomosis with standard care were conducted. Odds ratios (ORs) and 95% confidence interval (CIs) were used to assess the association between intraoperative testing and AL. RESULTS: A total of 23 studies totaling 7115 patients were included. Pooled analysis revealed intraoperative tests, for integrity (OR 0.52, 95% CI 0.34-0.82, P < .001) and perfusion (OR 0.40, 95% CI 0.22-0.752, P < .001) of the lower gastrointestinal tract anastomoses are associated with significantly lower AL rate. CONCLUSIONS: Intraoperative testing for either integrity or perfusion of anastomoses both reduce the AL rate. Studies looking at the combination of these two testing methods of anastomosis, especially intraoperative endoscopy, and indocyanine green fluorescence angiography may be very promising to further reduction of the AL.

Evaluation and Management of Hemorrhoids.

CASE SUMMARY: A 46-year-old otherwise healthy female patient presents with bright red blood during defecation and a lump protruding on defecation that requires manual reduction. She is the mother of 2 children and has a long history of constipation.

Relaxin Positively Influences Ischemia-Reperfusion Injury in Solid Organ Transplantation: A Comprehensive Review.

In recent decades, solid organ transplantation (SOT) has increased the survival and quality of life for patients with end-stage organ failure by providing a potentially long-term treatment option. Although the availability of organs for transplantation has increased throughout the years, the demand greatly outweighs the supply. One possible solution for this problem is to extend the potential donor pool by using extended criteria donors. However, organs from such donors are more prone to ischemia reperfusion injury (IRI) resulting in higher rates of delayed graft function, acute and chronic graft rejection and worse overall SOT outcomes. This can be overcome by further investigating donor preconditioning strategies, graft perfusion and storage and by finding novel therapeutic agents that could reduce IRI. relaxin (RLX) is a peptide hormone with antifibrotic, antioxidant, anti-inflammatory and cytoprotective properties. The main research until now focused on heart failure; however, several preclinical studies showed its potentials for reducing IRI in SOT. The aim of this comprehensive review is to overview currently available literature on the possible role of RLX in reducing IRI and its positive impact on SOT.

The problem of colorectal anastomosis safety.

INTRODUCTION: Anastomotic leakage (AL) remains one of the most threatening complications in colorectal surgery with the incidence of up to 20%. The aim of the study is to evaluate the safety and feasibility of novel - trimodal intraoperative colorectal anastomosis testing technique. METHODS AND ANALYSIS: This multi-center prospective cohort pilot study will include patients undergoing colorectal anastomosis formation below 15 cm from the anal verge. Trimodal anastomosis testing will include testing for blood supply by ICG fluorescence trans-abdominally and trans-anally, testing of mechanical integrity of anastomosis by air-leak and methylene blue leak tests and testing for tension. The primary outcome of the study will be AL rate at day 60. The secondary outcomes will include: the frequency of changed location of bowel resection; ileostomy rate; the rate of intraoperative AL; time, taken to perform trimodal anastomosis testing; postoperative morbidity and mortality; quality of life. DISCUSSION: Trimodal testing of colorectal anastomosis may be a novel and comprehensive way to investigate colorectal anastomosis and to reveal insufficient blood supply and integrity defects intraoperatively. Thus, prevention of these two most common causes of AL may lead to decreased rate of leakage. STUDY REGISTRATION: Clinicaltrials.gov (https://clinicaltrials.gov/): NCT03958500, May, 2019.

Factors Influencing Quality of Life during the First Trimester of Pregnancy: A Prospective Cohort Study.

Introduction: Pregnancy, delivery and postpartum periods are associated with fast changesleading to decreased self-confidence, anxiety, stress or even maternal depression impairing theirquality of life (QOL). Although considered important, QOL of women during pregnancy is poorlyunderstood. The aim of our study was to assess factors influencing QOL during first trimester ofpregnancy. The secondary goal of our study was to evaluate whether QOL during first trimester ofpregnancy is associated with newborn weight. Materials and methods: A prospective cohort studywas performed including pregnant women during the first trimester visit. Our questionnaireconsisted of the SF-36 QOL questionnaire, Wexner fecal incontinence scale, and other additionalinformation. The SF-36 questionnaire mental (MCS) and physical (PCS) health scores were used inorder to evaluate QOL of women during first trimester of pregnancy. Two multiple logisticregression models were created in order to determine independent variables that influence the QOL.Results: 440 pregnant women were included in the study. The two main domains that were used inthe study were MCS and PCS, their medians were 50.0 (25.0; 50.0) and 50.1 (39.4; 59.0) pointsrespectively. From the two logistic regression models we determined several independent factorsthat influence QOL of women during the first trimester of pregnancy. Additionally, we determinedthat women who reported worse QOL tended to give birth to newborns large for their gestationalage. Conclusions: We found several significant variables that influence QOL of women during thefirst trimester of pregnancy. We also found that that lower MCS and PCS scores during the firsttrimester are associated with newborns large for gestational age.

Gallstone Ileus: Management and Clinical Outcomes.

Background: Gallstone or biliary ileus is a late complication of gallstone disease. It accounts for 1%-4% of all bowel obstructions and is more common in elderly patients. The preferred treatment option is to mechanically remove the impacted stones. It is done surgically using open or laparoscopic approach and rarely, when stones are impacted in the colon, endoscopically. In this paper we present five consecutive cases of gallstone ileus and describe possible diagnostic and minimally invasive treatment options. Case presentation: During a five-month period a total of five patients were treated for gallstone ileus. All patients were female and from 48 to 87 years of age. Symptoms were not specific and common for all small bowel obstructions. Upon admission the patients also had unspecific laboratory findings-neutrophilic leukocytosis and various C-reactive protein concentrations, ranging from 8 to 347 mg/L. According to the hospital protocol, all patients initially underwent an abdominal ultrasound, which was inconclusive, and therefore every patient additionally had a CT scan with intravenous contrast. After these two diagnostic modalities one patient still did not have the definitive gallstone ileus diagnosis, as the ectopic stone was not visible. Four patients in our case series were treated using minimally invasive methods: in one case the stone was removed endoscopically, and laparoscopically in the other three. Treatment outcomes were good in four cases as the patients fully recovered, however one patient suffered a massive cerebral infarction after the operation and passed away. Conclusions: Gallstone ileus is a rare and difficult-to-diagnose condition. Management of these patients in every case should be individualized, as there are many options, each with their own advantages and disadvantages. We show that minimally invasive treatment such as colonoscopy or laparoscopy is possible in these cases.

Risk factors of developing the hungry bone syndrome after parathyroidectomy for primary hyperparathyroidism.

BACKGROUND: Around 13% of patients undergoing parathyroidectomy for primary hyperparathyroidism (PHPT) postoperatively develop a condition known as the hungry bone syndrome (HBS). Although the condition is quite prevalent, the research in this field is very limited. The aim of our study was to determine possible risk factors of developing HBS after parathyroidectomy for PHPT. MATERIALS AND METHODS: In this study we enrolled patients who underwent parathyroidectomy for PHPT from January 2005 to December 2016 and performed a retrospective analysis. We used the definition of HBS as hypocalcaemia with normal or elevated PTH values. Patients were divided into two groups by the postoperative HBS prevalence: patients with postoperative HBS and those without postoperative HBS. RESULTS: In all, 94 patients were included into the final analysis. We found that patients who developed HBS more often underwent parathyroidectomies simultaneously with a thyroid surgery, underwent longer operations (73.9 ± 41.7 vs. 102.4 ± 44.8 minutes; p = 0.001), and had heavier parathyroid glands removed (0.6 (0.3-8.0) vs. 0.8 (0.15-14.0) g; p = 0.041). Also, these patients had higher preoperative PTH values (15.3 (6.1-63.7) vs. 22.4 (9.2-47.8) pmol/l; p = 0.003). From the ROC curve of the preoperative PTH values and the development of the hungry bone syndrome (AUC = 0.721 (95% CI 0.59-0.85); p = 0.003) we found a 45 pmol/l PTH cut-off value that shows a 90% tendency to develop postoperative HBS. CONCLUSIONS: Patients undergoing longer parathyroidectomies and those with heavier removed parathyroid glands tend to develop HBS. A preoperative PTH value higher than 45 pmol/l determines an over 90% risk of developing HBS.

Fecal incontinence after transanal endoscopic microsurgery.

PURPOSE: Transanal endoscopic microsurgery (TEM) procedure could potentially influence the development of fecal incontinence later in life. The aim of our study was to assess long-term functional outcomes after TEM and to determine possible variables related to incontinence. METHODS: Patients, enrolled in a prospectively collected TEM operation database, were interviewed using a postal questionnaire. The questionnaire consisted of EuroQol (EQ)-5D-5L quality of life questionnaire, Wexner fecal incontinence grading scale, and additional questions about other perianal operations and obstetric history for women. We divided patients into two groups: no or minor fecal incontinence (Wexner score of 2 and less) and non-minor incontinence (Wexner score of 3 or more). RESULTS: One hundred thirty-two patients were included in the study. Patients' median follow-up time was 96 (12-168) months from their operation. Thirty-eight patients (28.8%) reported Wexner score of 3 or more, and they reported significantly worse quality of life in all tested life spheres. They were older at the time of the operation (63 (18-82) vs. 68 (50-89) years; p = 0.004), underwent longer operations (50 (10-140) vs. 60 (15-210) min; p = 0.017), and more often were operated for malignant lesions (17 (18.3%) vs. 14 (36.8%); p = 0.040). Older age at the time of operation was an independent risk factor in multivariate model (OR 1.057, 95% CI 1.010-1.106; p = 0.016). CONCLUSIONS: Fecal incontinence after TEM is more common than thought previously, resulting in significantly impaired quality of life. Older age at the time of operation was an independent risk factor for developing significant fecal incontinence.