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.

Role of Oxaliplatin in the Neoadjuvant Concurrent Chemoradiotherapy in Locally Advanced Rectal Cancer: a Review of Evidence.

The treatment of locally advanced rectal cancer (LARC) is a challenging situation for radiation oncologists and colorectal surgeons. Most current approaches recommend neoadjuvant fluorouracil or capecitabine-based chemoradiotherapy followed by surgery as a standard of care. Intensification of concurrent chemotherapy by adding oxaliplatin to fluorouracil or capecitabine backbone to get better outcomes is the matter that has remained unresolved. In this review, we searched Medline and Google Scholar databases and selected 28 prospective phase II and III clinical trials that addressed this question. We discussed the potential advantages and drawbacks of incorporating oxaliplatin into concurrent chemoradiation therapy. We tried to define whether adding oxaliplatin to concurrent chemoradiation with excellent performance and high-risk features benefits some subpopulations. The available literature suggests that by adding oxaliplatin there are some benefits in enhancing response to neoadjuvant chemoradiotherapy, however, without any translated improvements in long-term outcomes including overall and disease-free survival.

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.

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.

Surgical management of retrorectal tumors: a single-center 12 years' experience.

Purpose: Retrorectal tumors (RTs) are rare tumors that arise in the space between the mesorectum and the pelvic wall and often originate in embryonic tissues. The primary treatment for these tumors is complete excision surgery, and choosing the best surgical approach is very important. Methods: In this study, we retrospectively collected the data of 15 patients with RTs who underwent surgery in the surgical ward of Imam Khomeini Hospital in Tehran for 12 years to share our experiences of patients' treatment and compare different surgical approaches. Results: A total of 5 tumors were malignant, 10 were benign, and most of the tumors were congenital. Malignant tumors were seen in older patients. Three surgical procedures were performed on patients. Three patients underwent abdominal approach surgery, and 8 patients underwent posterior surgery. A combined surgical approach was performed on 4 patients. Two patients underwent laparoscopic surgery. The abdominal approach had the least long-term complication, and the combined approach had the most complications; laparoscopic surgery reduced the length of hospital stay and complications after surgery. Conclusion: A multidisciplinary team collaboration using magnetic resonance imaging details is necessary to determine a surgical treatment approach. It could reduce the need for a preoperative biopsy. However, every approach has its advantages and disadvantages. In the main, they have no superiority over each other, and individualized treatment is the key.

Surgical management of a solitary metastatic ovarian adenocarcinoma with colonic origin presenting as gigantic bilateral ovarian masses.

Metastatic ovarian tumors with a gastrointestinal origin have always been a challenge in surgery; in many cases, the primary tumor is diagnosed after the metastasis. This case was presented with bilateral abdominal masses, which were adenocarcinomas originating from gastrointestinal tract. Following colonoscopy and finding a mass, total colectomy was performed.

Advanced Regenerative Medicine Strategies for Treatment of Perianal Fistula in Crohn's Disease.

Regenerative medicine is an emerging therapeutic method that aims to reconstruct tissues and organs. This advanced therapeutic approach has demonstrated great potential in addressing the limitations of medical and surgical procedures for treating perineal fistula in patients with Crohn's disease. Recent developments in stem cell technology have led to a massive good manufacturing practices (GMPs) production of various stem cells, including mesenchymal and embryonic cells, along with induction of pluripotent stem cells to repair damaged tissues in the fistula. The recent advances in separation and purification of exosomes, as biologic nanovesicles carrying anti-inflammatory and regenerative agents, have made them powerful tools to treat this inflammatory disease. Further, tremendous advances in nanotechnology, biomaterials, and scaffold fabrication methods enable tissue engineering methods to synthesize tissue-like structures to assist surgical techniques. This review focuses on advanced regenerative-based methods including stem cell therapy, exosome therapy, and tissue engineering used in the treatment of perianal fistula. Relevant in vitro and in vivo studies and the latest innovations in implementation of regenerative medicine for this disease are also separately reviewed. Additionally, current challenges regarding implementation of g stem cells, exosomes, and tissue engineering methods for bridging the gaps between laboratory findings and clinic application will be discussed.

Introduction of a handmade vacuum-assisted sponge drain for the treatment of anastomotic leakage after low anterior rectal resection.

PURPOSE: Anastomotic leakage, a known major postoperative complication, potentially leads to readmission, reoperation, and increased mortality rates in patients, such as rectal cancer patients following a low anterior resection (LAR). Currently, vacuum-assisted closure, as featured by B-Braun (B-Braun Medical B.V.), is already being used for the treatment of gastrointestinal leakages and fistulas. The main aim of this study was to introduce a novel method for creating a vacuum-assisted drain for the treatment of anastomotic leakage after LAR. METHODS: All 10 patients, who underwent LAR surgery from 2018 to 2019, were diagnosed with anastomotic leakage and had received neoadjuvant chemotherapy prior to surgery. Therefore, patients were treated with a handmade vacuum-assisted drain and were revisited every 5 to 7 days for further evaluations and drain replacement until leakage resolution. Physical features of cavity, time of diagnose, and duration of treatment were analyzed correspondingly. The handmade vacuum-assisted sponge drain was prepared for each patient in each session of follow-up. RESULTS: Eight out of 10 patients experienced complete closure of the defect. The mean delay time from the day of operation to the diagnosis of anastomotic leakage was 61.0±80.4 days while the mean time for leakage closure was 117.6±68.3 days. Eventually, 7 cases underwent ileostomy reversal with no complications during a 3-month follow-up. CONCLUSION: In this study, we evaluated the healing process of anastomotic leakage after the usage of a handmade vacuum-assisted sponge drain in a case series method. In our trial, we provided an innovative cost-benefit method easily applicable in the operating room.

Splenic flexure volvulus, a rare etiology of colonic obstruction: Case report.

INTRODUCTION: Splenic flexure volvulus (SFV) occurs as a result of twisting or torsion of a redundant colon around its mesentery. The SFV can be divided into primary and secondary types. PRESENTATION OF CASE: An 82-year-old woman with a previous history of Parkinson's disease, diabetes mellitus and hypertension presented with a primary complaimt of obstipation and progressive abdominal pain. Abdomen was grossly distended and tympanic with generalized tenderness. The rectum was empty on digital rectal examination. Complete blood count showed leuckocytosis and neutrophlia. Plain abdominal X-rays showed distented cecum and ascending colon without any air in the gut distal to the splenic flexure. Regarding her unstable condition even aftre fluid resuscitation, she was transferred to the operating room. SFV was found and the standard left hemicolectomy was performed and bowel continiuity was established with primary anastomis of remained colonic ends. Postoperative period was uneventfull. DISCUSSION: The splenic flexure is strictly attached to the adjacent organs so its volvulus is rare. Most cases of adult SFV have an underlying disease associated with chronic constipation. Diagnosis of volvulus is suspected based on the history, clinical exam, and imaging. The initial and urgent treatment of SFV, if there are no signs of ischemia or perforation, may be conservative with endoscopic detorsion. Gangrenous bowel should not be detorted and should be resected with primary anastomosis or a diverting stoma. CONCLUSION: SFV should be considered as a possible diagnosis of chronic constipation which might be diagnosed with plain abdominal Xray in non emergent condition. Special attention should be given to the medication history of the patient as the anticholinergic agents propagate normal pristaltis.