Umbelliprenin improved anti-proliferative effects of ionizing radiation on adult T-cell leukemia/lymphoma cells via interaction with CDK6; an in vitro and in silico study.

Adult T-cell leukemia/lymphoma (ATL) is an aggressive malignancy with poor survival rates. The efficacy of radiotherapy in ATL needs enhancement with radiosensitizing agents. This study investigated whether umbelliprenin (UMB) could improve the therapeutic effects of ionizing radiation (IR) in ATL cells. UMB, a naturally occurring prenylated coumarin, exhibits anticancer properties and has shown synergistic effects when combined with chemotherapeutic drugs. Despite this promising profile, there is a notable lack of research on its potential combinatorial effects with IR, particularly for ATL treatment. UMB was extracted from Ferula persica using thin layer chromatography. MT-2 cells were treated with UMB alone and in combination with various doses of IR, and cell proliferation was assessed via alamarBlue assay. Flow cytometry with annexin V and PI staining was conducted, and candidate gene expression was analyzed by qPCR. In silico analysis involved identifying pathogenic targets of ATL, constructing protein-protein interaction (PPI) networks, and evaluating CDK6 expression in MT-2 cells. Molecular docking was used to determine the interaction between UMB and CDK6. The alamarBlue assay and flow cytometry showed that pretreating ATL cells with UMB significantly (p < .0001) enhanced anti-proliferative effects of IR. The combination index indicated a synergistic effect between UMB and IR. qPCR revealed significant (p < .0001) downregulation of CD44, CDK6, c-MYC, and cFLIPL, and overexpression of cFLIPS. Computational analysis identified CDK6 as a hub gene in the PPI network, and CDK6 overexpression was confirmed in MT-2 cells. Molecular docking revealed a favorable binding interaction between UMB and the ATP-binding site of CDK6, with a JAMDA score of -2.131, surpassing the control selonsertib. The current study provides evidence that UMB enhances the anti-proliferative effects of IR on ATL cells, and highlights the significance of targeting CDK6 in combinatorial approaches.

Localized Administration of Mesenchymal Stem Cell-Derived Exosomes for the Treatment of Refractory Perianal Fistula in Crohn's Disease Patients: A Phase II Clinical Trial.

BACKGROUND: Crohn's disease perianal fistulae are often resistant to standard anti-TNF-α therapies. Mesenchymal stem cell (MSC)-derived exosomes are extracellular vesicles that have highly potent anti-inflammatory effects, and the previous phase of this study demonstrated their safety in the treatment of refractory perianal fistulas. OBJECTIVE: To evaluate the efficacy of mesenchymal stem cell-derived exosomes for the treatment of refractory perianal fistulas. DESIGN: Nonrandomized, nonblinded single-center phase II clinical trial. SETTINGS: Tertiary university hospital. PATIENTS: Twenty-three patients were enrolled, 20 of whom completed the study. Refractory perianal fistula was defined as resistance to at least one course of treatment with anti-tumor necrosis facto-α therapy. INTERVENTIONS: After clinical assessment and magnetic resonance imaging, the patients were subjected to general anesthesia, and 5 mL of exosome solution was injected directly into the fistula tracts. The injections were repeated three times at 2-month intervals, and patients were followed monthly for 6 months after the last injection. Tissue samples from the tracts were obtained before each injection and subjected to immunohistopathological assessment. MRI data were obtained before and six months after the last injection. MAIN OUTCOME MEASURES: The primary outcome of this study was fistula tract closure on clinical examination and magnetic resonance imaging. The secondary outcome was an improvement in the discharge from the tracts. RESULTS: Fistula tracts were fully closed in 12 (60%) of the patients. Four patients showed clinical improvement, with some tracts remaining open, and four patients were completely resistant to treatment. A total of 43 fistula tracts were treated during the trial, 30 (69.7%) of which showed complete closure. Histopathological analysis revealed substantial reductions in local inflammation and signs of enhanced tissue regeneration. Immunohistochemical analysis of cluster of differentiation-68, 20 and 31 reaffirmed these results. CONCLUSIONS: MSC-derived exosomes are safe and effective for treating refractory perianal fistulas in patients with Crohn's disease. See Video Abstract.

Predictive value of flexible proctosigmoidoscopy and laboratory findings for complete clinical responses after neoadjuvant chemoradiotherapy in patients with locally advanced primary rectal cancer: a retrospective cohort study.

PURPOSE: Colorectal cancer is the second leading cause of cancer death worldwide. Standard treatments for locally advanced rectal cancer include neoadjuvant chemoradiotherapy and total mesorectal excision (TME), which are associated with significant morbidity. After neoadjuvant therapy, one-third of patients achieve a pathological complete response (pCR) and are eligible for a watch-and-wait approach without TME. The purpose of this study was to determine the potential predictors of pCR before surgery. METHODS: The demographic, clinical, and endoscopic data of 119 patients with primary locally advanced rectal cancer without distant metastasis who underwent restaging endoscopy and TME 6-8 weeks after the end of neoadjuvant therapy were collected. The absence of tumor cells in the histological examination of the TME specimen after neoadjuvant therapy was considered pCR. Binary logistic regression and receiver operating characteristic curves were utilized for analysis. RESULTS: According to the multivariate logistic regression analysis, flattening of marginal tumor swelling (p value < 0.001, odds ratio = 100.605) emerged as an independent predictor of pCR in rectal cancer patients. Additionally, receiver operating characteristic curve analysis revealed that lower preoperative carcinoembryonic antigen and erythrocyte sedimentation rate levels predict pCR, with cutoffs of 2.15 ng/ml and 19.0 mm/h, respectively. CONCLUSION: Carcinoembryonic antigen and erythrocyte sedimentation rate, along with the presence of flattening of marginal tumor swelling, can predict pCR after neoadjuvant chemoradiotherapy in patients with primary rectal cancer. These factors offer a potential method for selecting candidates for conservative treatment based on endoscopic and laboratory findings.

Analyzing quality of life after low anterior resection for rectal cancer.

BACKGROUND: Rectal cancer is one of the most common cancers worldwide that imposes high costs on patients and the healthcare system while also having a significant impact on the patient's quality of life (QoL). AIM: We aimed to assess the QoL of rectal cancer patients undergoing lower anterior resection (LAR) and evaluate potential confounding factors. METHODS: In this cross-sectional study, we included patients undergoing neo-adjuvant chemotherapy followed by LAR, diverting ileostomy, and adjuvant chemotherapy. Six months after stoma reversal, QoL was assessed using a cancer-specific core questionnaire EORTC QLQ-C30 and also a colorectal cancer module EORTC QLQ-CR29. Linear and quantile regression models were used to examine associations of QoL and patients' demographical and clinical features. RESULTS: The study population comprised 210 patients with an average age of 61.9 ± 11.0 (range: 37-85) and 112 (53.3%) male patients. The higher tumor stage increases the QoL of patients by reducing diarrhea, loss of appetite, defecation problems, and stool frequency. Based on the linear regression analysis, a farther distance of the anastomosis from the anal verge (AV) was correlated with lower symptom scores and higher QoL. Also, at the 75th percentile cut-off of the QLQ-CR29 scores, a higher N stage of the tumor was correlated with higher QoL based on functional subscale (coefficient = 3.032, P = 0.016). CONCLUSIONS: QoL of patients after LAR for rectal cancer is significantly associated with the distance of the anastomosis site from the AV.

Gross morphologic features of surgical specimen in rectal cancer patients with pathological complete response following neoadjuvant chemoradiotherapy: A cross-sectional study.

BACKGROUND: pathological complete response (pCR) is achieved in 10%-30% of rectal cancer patients following neoadjuvant chemoradiotherapy and surgery. Residual mucosal abnormalities, which make patients ineligible for nonoperative management, may not be an accurate indicator of the pCR. The purpose of this study was to report the gross findings of rectal cancer patients with pathological complete responses. METHODS: This study was conducted at Tehran University of Medical Sciences, Tehran, Iran. A total of 130 patients with rectal adenocarcinoma, treated by neoadjuvant chemoradiotherapy, followed by surgical resection between March 2007, and March 2017, with a surgical pathology report of pCR, were included. Patients' demographics and pretreatment tumor characteristics were collected from the medical records. Data regarding residual mucosal abnormalities were extracted from postoperative surgical pathology reports. Abnormal findings were reported as "ulcer" or " non-ulcerative lesion". RESULTS: One hundred and fifteen patients (88.5%; 95% CI: 81.7%-93.4%) had at least one abnormal finding in the gross examination, including ulcer or non-ulcerative lesion (any mucosal abnormalities other than ulcers, including polyps, telangiectasia, etc.). Patients with higher-stage tumors had a higher chance of having an ulcerative lesion (p = 0.05). Younger patients tended to have deeper layers of involvement (p = 0.013). Patients with different gross findings were not significantly different regarding baseline characteristics, except for the pretreatment stage, where patients with a higher stage had higher odds of having ulcerative lesions. CONCLUSIONS: Most rectal cancer patients achieving a pCR exhibit abnormalities on gross examination. The higher pretreatment stages were significantly associated with gross abnormalities especially ulcers.

Immune gene polymorphisms associated with poor response to platelet transfusion and recombinant factor VII administration in Glanzmann thrombasthenia.

INTRODUCTION: Poor response to platelet and recombinant factor VII administration is a major problem in patients with Glanzmann Thrombasthenia (GT). The risk factors associated with poor response to treatment in these patients are unknown. Some genetic variations of cytokines may contribute to therapy resistance. AIMS: We evaluated, for the first time, whether genetic polymorphisms on cytokine genes are related to poor treatment response in GT patients. METHODS: We enrolled 30 patients with GT (15 resistant and 15 non-resistant) and 100 healthy controls. Gene polymorphisms of IL-10 and TNF-α were analysed using TaqMan Realtime PCR, and IL-1, IL-1R1 and IL-1RN were investigated with the RFLP method. In-silico analyses were performed to predict the potential impact of these polymorphisms. RESULTS: In the resistant group, all patients had a variant of the IL-10 gene at the -1082 position (rs1800896), with a GG genotype that was significantly more frequent than the non-resistant group. Analysis between healthy controls and GT patients revealed a probable correlation between rs3783550, rs3783553, rs3917356 and rs2234463 and GT. The In-silico study indicated that TNF-α rs1800629 and IL-10 rs1800896 polymorphisms result in different allelic expressions which may contribute to poor response to therapy. CONCLUSIONS: These findings suggest that polymorphisms in the IL-10 and IL-1 receptor antagonist genes may play a role in poor therapy response in GT patients. In addition, some polymorphisms in IL-1α, IL1-ß, IL-1R1 and IL-R antagonists might be involved in the GT progression.

Comparison of hand-sewn anterior repair, resection and hand-sewn anastomosis, resection and stapled anastomosis techniques for the reversal of diverting loop ileostomy after low anterior rectal resection: a randomized clinical trial.

BACKGROUND: Low anterior resection in patients with rectal cancer may require a defunctioning loop ileostomy formation that requires closure after a period of time. There are three common techniques for ileostomy closure: anterior repair (AR or fold-over closure), resection and hand-sewn anastomosis (RHA), and resection and stapled anastomosis (RSA). We aimed to compare them on the basis of operative and postoperative features. METHODS: Patients with rectal cancer who underwent low anterior resection without complications were included in this study and randomly assigned to three parallel groups to undergo loop ileostomy closure via either AR, RHA, or RSA. Early and late outcomes were gathered from all included patients. RESULTS: Among 93 patients with a mean age of 56.21 ± 11.78 years, consisting of 58 (62.4%) men, 31 patients underwent AR, 30 patients RHA, and 32 patients RSA. There was no significant difference among the groups regarding the frequency and location of intraoperative injuries (P = 0.157). The AR groups demonstrated significantly less consumption of gauzes following intraoperative bleeding compared to the two others groups. The results showed that the duration of surgery in the RSA was significantly shorter than in the AR or RHA group (both P < 0.001). Regarding postoperative course, only one case of hematoma and two cases of surgical wound infection occurred in the RHA group. Anastomotic leakage and complete or partial obstruction did not occur in any group of patients. Latent postoperative complications did not occur in any group of patients. The median time between surgery and discharge as well as the interval until first gas passage, first defecation, oral tolerated liquid diet, as well as oral tolerated soft and regular diet in the AR group were significantly lower than in the two other groups (both P < 0.001). However, there was no statistical difference in these intervals between the RHA and RSA groups. CONCLUSIONS: Resection and stapled anastomosis had the shortest duration among the three techniques; however, anterior repair had faster recovery, including earlier tolerated oral diet, gas passing and defecation, and discharge, in comparison with the other techniques. TRIAL REGISTRATION: Trial registration number IRCT20120129008861N5.

The impact of circular stapler size on the risk of anastomotic stricture following total mesorectal excision in rectal cancer patients: A retrospective cross-sectional study.

Introduction: Colorectal cancer (CRC) surgery complications are a major issue affecting morbidity and mortality rates. Anastomotic stricture, which occurs in almost 30% of patients after surgery for rectal cancer, is one of the most serious but underreported side effects. In this study, we tried to assess the effect of stapler size on anastomotic stricture rate. Materials and Methods: At our facility, all patients underwent low anterior resections (LAR) performed using an open laparotomy technique. A contour-curved stapler and an end-to-end anastomosis (EEA) circular stapler were used in the double stapling technique (DST). All patients also underwent a protective loop ileostomy. Patients who developed stricture following leakage were excluded. Results: This study comprised a total of 173 rectal cancer patients. A 29-mm circle stapler was used to anastomose 77 patients (44.5%), while a 31-mm circular stapler was used to anastomose 96 patients (55.5%). Six individuals experienced strictures; two had a 29 mm stamper and four (4.4%) had a 31 mm one. There was no significant difference between the two groups (p:0.575). On aggregate, 8 patients experienced leakage; 3 (3.8%) of these patients received treatment with a 29 mm stapler, whereas 5 (5.2%) received treatment with a 31 mm stapler. Conclusion: this study found no statistically significant difference in the stricture rates and stapler size. The findings of this study provide credibility to the notion that in rectal cancer patients having LAR, strictures can be safely avoided by performing the anastomoses with both staplers.

Biomedical properties and hemostatic efficacy of polyvinyl alcohol (PVA) based hydrogel in experimental rat liver injury model.

PURPOSE: Bleeding is a leading cause of mortality and morbidity in the trauma and surgery field, using effective hemostatic agents can help us reduce bleeding especially in parenchymal hemorrhage. Nowadays polyvinyl alcohol (PVA) is known as a safe candidate for wound dressing and maybe a hemostatic agent. PVA-based hydrogel is a popular biocompatible material in the biomedical field especially when it has high water absorption. In this study, we investigated the PVA hydrogel's mechanical and biological properties as well as its hemostatic potential in parenchymal bleeding. METHODS: PVA hydrogel had made by the freeze-thawing approach, we used PVA hydrogel in comparison to standard treatment to investigate hemostatic potency. Also, we performed MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) tests to survey PVA cellular toxicity. After an acute liver injury, two groups of 12 rats were treated with PVA hydrogel or standard treatment with sterile gauze. The results including the time and volume of bleeding, and the time and survival rate of the rats were measured and compared. RESULTS: We saw that PVA hydrogel was safe with no cellular toxicity in the MTT assay. Regarding efficacy, PVA hydrogel increased rats' survival after bleeding from 75% to 91.7%, and decreased bleeding time (p: 0.015), and bleeding volume (p: 0.03) compared to the control group. CONCLUSION: Polyvinyl alcohol is safe. It has good biological properties with no cellular toxicity and has a significant hemostatic effect and can be regarded in control of parenchymal hemorrhage.

Evaluation of the Farsi-translated Hemorrhoidal Disease Symptom Score and Short Health Scale questionnaires in patients with hemorrhoid disease: A cross-sectional study.

Background and Aims: The Hemorrhoidal Disease Symptom Score (HDSS) is a tool that is scored based on five main symptoms: pain, bleeding, itching, soiling, and prolapse. Furthermore, the Short Health Scale (SHS) is a measurement tool of subjective health and health-related quality of life. This study was performed to validate the Farsi-translated Hemorrhoidal Disease Symptom Score (HDSS), and Scale Short Health Scale adapted for hemorrhoidal disease (SHS-HD) as a measure of symptom severity in patients with hemorrhoid disease. Methods: In this study, HDSS and SHS-HD were translated into Farsi. Participants with confirmed hemorrhoid disease completed the questionnaire. Subsequently, the questionnaire's discriminative validity, convergent validity, reliability, sensitivity, and specificity were evaluated. Results: Data from 31 patients were analyzed (mean age 39.68; 71% male). The results of the analysis showed good internal consistency as Cronbach's α for HDSS and SHS were 0.994 and 0.995 respectively. Spearman's correlation coefficient for the test-retest comparison was 0.986 (p < 0.01). The responses demonstrated good convergent validity. Moreover, the comprehension and suitability of each question were rated as excellent (Pearson's correlation coefficient = 0.3). Conclusions: Our findings revealed that the Farsi translation of the HDSS and SHS-HD can be a valuable tool for evaluating the symptom severity in patients with hemorrhoid disease.

Translation, cross-cultural adaptation, and psychometric evaluation of the Persian (Farsi) version of the QoLAF (quality of life in patients with anal fistula) questionnaire.

INTRODUCTION: The effective treatment of anal fistulas almost always requires surgical intervention, which could be accompanied by post-operative complications, and affect the quality of life of patients. This study aimed to cross-culturally adapt the Persian version of the Quality of Life in patients with Anal Fistula questionnaire and evaluate its validity and reliability. MATERIALS AND METHODS: Sixty patients with a mean age of 44 years ranging from 21 to 72 years entered the study. Forty-seven participants were men, and thirteen were women. After performing a scientific translation of the questionnaire based on Beaton's guidelines for cross-cultural adaptation and after extensive reviews by experts and specialists, the final version of the questionnaire was obtained. Then, 60 questionnaires (100%) were filled out by the participants (n = 60) and retrieved during a 7 to 21-day period. Data were collected and analyzed. Finally, according to the obtained data, the validity and reliability of the questionnaire were calculated. RESULTS: Cross-cultural adaptation of the translated questionnaire was verified by the expert committee. The results showed perfect internal consistency (Cronbach alpha = 0.842), and external consistency (intraclass correlation coefficient = 0.800; P<0.001). Spearman correlation coefficient between test and retest was reported to be 0.980 (P-value <0.01), confirming the temporal stability of the translated questionnaire. The interrater reliability based on Cohen's kappa coefficient also demonstrated a perfect degree of agreement between two peer variables (Kappa = 0.889; P<0.001). CONCLUSION: The Persian translation of the Quality of Life in patients with the Anal Fistula questionnaire was proven to be valid and reliable for the evaluation of the QoL of patients with anal fistula.

Assessment of the efficacy of Handmade Vacuum-Assisted Sponge Drain for Treatment of Anastomotic leakage after Low Anterior Rectal Resection.

Anastomotic leakage is one of the major complications of colorectal surgery, which might lead to reoperation, increased hospital stays, further intervention and mortality. Vacuum-assisted closure by devices such as Endo-SPONGE® produced by (B-Braun Medical B.V.) is currently being used to treat leakage and fistula. In this study, we aimed to assess the handmade vacuum-assisted sponge drain for anastomotic leakage following low anterior resection. This prospective study included 22 patients who had undergone sponge drain placement to treat anastomotic leakage. All patients had anastomotic leaks or defects after left anterior rectal resection (LAR) without ileostomy. They were treated with neo-adjuvant chemotherapy before the surgery and then subjected to rigid recto-sigmoidoscopy for 30 days following the operation. Any sign of leakage, such as perianal and pelvic pain, was immediately identified and followed up with a CT scan and another recto-sigmoidoscopy. Twenty-two patients were enrolled in this study, 12 men (54.5%) and 10 women (47.4%). All patients had received neo-adjuvant chemotherapy with an average follow-up of 22.30 ± 3.81. 75% of patients (15 cases) were successfully treated, and 17 patients (85%) underwent successful ostomy closure. Treatment failed in 5 patients (25%), including three men and two women. This study shows that handmade vacuum-assisted sponge drain is a cost-effective method of anastomotic leakage management with efficacy similar to that of Endo-SPONGE®.

Evaluation of colonic anastomosis healing using hybrid nanosheets containing molybdenum disulfide (MOS2) scaffold of human placental amniotic membrane and polycaprolactone (PCL) in rat animal model.

Anastomosis is a standard technique following different conditions such as obstruction, tumor, and trauma. Obstruction, adhesion, or anastomosis leakage can be some of its complications. To improve healing and prevent postoperative complications, we design a hybrid scaffold containing acellular human amniotic membranes and polycaprolactone-molybdenum disulfide nanosheets for colon anastomosis. The animal model of colocolonic anastomosis was performed on two groups of rats: control and scaffold. The hybrid scaffold was warped around the anastomosis site in the scaffold group. Samples from the anastomosis site were resected on the third and seventh postoperative days for histopathological and molecular assessments. Histopathologic score and burst pressure had shown significant improvement in the scaffold group. No mortality and anastomosis leakage was reported in the scaffold group. In addition, inflammatory markers were significantly decreased, while anti-inflammatory cytokines were increased in the scaffold group. The result indicates that our hybrid scaffold is a proper choice for colorectal anastomosis repair by declining postoperative complications and accelerating healing.

Evaluation of the effectiveness of prophylactic omentopexy during laparoscopic insertion of peritoneal dialysis catheter: a case-control clinical trial.

INTRODUCTION: The laparoscopic omentopexy has been described for the prevention of peritoneal dialysis catheter obstruction due to omental wrapping of the catheter. As there are some controversies and limited data regarding the outcomes of prophylactic omentopexy, we designed a study to evaluate the efficacy of prophylactic omentopexy in preventing catheter dysfunction in patients undergoing laparoscopic catheter placement. MATERIALS AND METHODS: In this randomized clinical trial, patients with end-stage renal disease during 3 months were divided into two groups of peritoneal dialysis catheter implants with and without omentopexy and subsequently evaluated regarding postoperative features. RESULTS: A total of 43 patients were evaluated, including 22 undergoing prophylactic omentopexies. There was no significant difference among the baseline features of the patients. There was also no significant difference regarding postoperative features, including peritonitis, leakage, reoperation, need for catheter removal, and mortality. CONCLUSION: Prophylactic omentopexy did not cause any significant differences in complications. In addition, there was no benefit for decreasing postoperative outflow obstruction due to omental wrapping following peritoneal dialysis catheter insertion.

Investigating the Expression Pattern of the SETMAR Gene Transcript Variants in Childhood Acute Leukemia: Revisiting an Old Gene.

BACKGROUND: The chimeric enzyme SETMAR (or Metnase) has been associated with several DNA processes, including DNA damage repair through the non-homologous joining pathway and suppression of chromosomal translocation in mouse fibroblasts. SETMAR overexpression has been reported in certain cancers suggesting that it might contribute to the establishment or progression of these cancers. In leukemia, the SETMAR gene transcript variants have not been widely studied. Therefore, this study aimed to quantify 3 predominant SETMAR variants in 2 types of childhood acute leukemia, acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). METHODS: In this study, using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), the relative expression of 3 SETMAR transcript variants (Var 1, Var 2, and Var A) were evaluated in the bone marrow samples collected from 30 newly diagnosed patients with AML, 65 newly diagnosed patients with ALL, and 15 healthy individuals. RESULTS: The expression of SETMAR variants 1 and A were significantly higher in AML patients compared with controls ( P =0.02, and P =0.009, respectively). Variant A expression was significantly higher in ALL compared with controls ( P =0.003). When comparing the expression in translocation-positive and negative subgroups, the expression of variant 1 was significantly higher in translocation-positive ALL patients ( P =0.03). The variants' distribution patterns differed concerning translocation status ( P =0.041), as variants 1 and A were dominant in the translocation-positive ALL group, and variant 2 was more prevalent in translocation-negative ones. CONCLUSIONS: According to the results, SETMAR showed increased expression in pediatric acute leukemia's bone marrow samples, indicating a role for this molecule in leukemia pathogenesis. As this is the first report of SETMAR expression in pediatric leukemias, further studies are needed to investigate the causality of this association.

Safety and efficacy of injection of human placenta mesenchymal stem cells derived exosomes for treatment of complex perianal fistula in non-Crohn's cases: Clinical trial phase I.

BACKGROUND AND AIM: A perianal fistula is an abnormal tract that connects anal canal to skin. Current medical and surgical interventions have a high failure rate particularly in complex and refractory cases. MSC-derived exosomes have demonstrated immunomodulatory effects without the conventional complications; hence, in this study, we evaluated the safety of their application for complex perianal fistula. METHODS: Placenta-derived MSCs were cultured, and exosomes were isolated using ultracentrifugation. Exosome injections were administered in the operating room to 11 patients with complex perianal fistula (presence of fistulas for at least 1 year alongside medical and surgical treatment). The patients were followed for 6 months, and the patients were evaluated using physical examination, face-to-face interviews, and magnetic resonance imaging (MRI). RESULTS: Among 11 patients only one did not show any improvement upon physical examination. Five patients showed complete tract resolve. While the discharge was stopped in eight patients, two patients showed only reduction. None of the patients showed any acute or latent allergic reaction or injection related complications. CONCLUSION: Administration of exosomes isolated from MSCs demonstrates safety and a satisfactory therapeutic effect in treatment complex perianal fistulae; therefore, it can be a candidate for future studies and might play a significant role in treatment.

Hand-sewn direct repair versus resection and hand-sewn anastomosis techniques for the reversal of diverting loop ileostomy after lower anterior rectal resection surgery: A randomized clinical trial.

INTRODUCTION: Several techniques have been proposed for the closure of loop ileostomy. This is the first study comparing bowel function and outcomes of two different hand-sewn surgical techniques used for the closure of diverting protective loop ileostomy. METHOD: In this prospective, randomized, double-blind clinical trial, 40 patients with a history of rectal cancer, low anterior resection, and diverting loop ileostomy who were candidates for ileostomy reversal were included and randomly assigned into two groups, hand-sewn direct repair of the ileal defect (group A) and resection and hand-sewn anastomosis of the ileum (group B). RESULTS: The mean age of patients was 56.42 and 52.10 years in groups A and B, respectively. Regarding early postoperative period, group A developed earlier first gas passage (1.68 vs. 2.25 days, p = 0.041) and stool passage (2.10 vs. 2.80 days, p = 0.032). Group A also revealed shorter operating time (83.68 vs. 89.50 min, p = 0.040) and hospital stay (4.73 vs. 6.80 days, p = 0.001). None of the participants in both groups developed signs of bowel obstruction during the early and late postoperative follow-up period. CONCLUSIONS: Direct hand-sewn repair for the closure of diverting loop ileostomy is a safe technique with better postoperative bowel function, oral diet tolerance, and less hospital stay compared to resection and hand-sewn anastomosis of the ileum.

Prognostic Factors of Disease Recurrence and Overall Survival Following Curative Resection of Colon Cancer: A 10-year Cohort from a Referral Center.

Background: The growing incidence of colorectal cancer around the world highlights the significance of tumor recurrence and patient survival as 2 key elements of patient therapy. We aimed to study the factors linked with disease recurrence and survival in colon cancer. Methods: Patients with colon cancer who underwent tumor excision as their primary treatment were enrolled in this prospective cohort and monitored for 10 years. Various demographic and clinicopathologic factors of these patients were studied in association with the 2 primary outcomes of this study, including tumor recurrence and patient survival. Statistical tests and survival analysis were utilized to explore the study aims. Results: An overall number of 113 patients were included in this survey with a mean age of 54.7 (±SD, 14.1), and most of the patients were men (56.6%). The mean follow-up period was 28.3 (±25.5) months. Tumor recurrence occurred in 32 (28.3%) patients in the study period. The estimated mean survival of patients was 54.9 (95% CI, 45.3-64.4) months. N staging ( p = 0.036), T staging ( p = 0.009), and pathologic staging (P = .004) were the significant pathological factors to higher tumor recurrence and lower survival rates. Conclusion: Advanced tumor staging led to increased disease recurrence and lower survival of colon cancer patients in this survey. Further public health screening and education programs are needed to improve the early detection and prognosis of these patients in Iran.

Evaluating the safety and efficacy of mesenchymal stem cell-derived exosomes for treatment of refractory perianal fistula in IBD patients: clinical trial phase I.

Background: Exosome administration is a novel medical approach that promises excellent immunomodulatory properties without the conventional side effects of current antitumor necrosis factor drugs and stem cells. This study aimed to assess the safety and efficacy of using mesenchymal stem cell (MSC) exosomes to treat refractory fistulas in patients with inflammatory bowel disease. Methods: MSCs were derived from the umbilical cords and their exosomes were isolated. Five patients with refractory perianal Crohn's disease fistulas with a median age of 35 years (range 31-47 years) were enrolled in the study. Exosome injections were administered in the operating room to patients with refractory fistula (fistulas that are irresponsive to anti-tumor necrosis factor-α administration within 6 months). Six months later, a physical examination, face-to-face interviews, and magnetic resonance imaging were employed to evaluate the therapy responses of patients. Results: The outcomes within 6 months after initiation of therapy showed that four patients had responded to therapy. Three patients who received exosome injections exhibited complete healing, while one reported no improvement and active discharge from the fistula site. In addition, five patients (100%) reported neither systemic nor local adverse effects. Conclusions: Injection of exosomes extracted from MSCs demonstrates safety and a satisfactory therapeutic effect, as evidenced in this and other studies, and may play a significant role in the future treatment of gastrointestinal fistulas.