Real-World Long-Term Persistence and Surgical Procedure-Free Period Among Bio-naïve Patients with Crohn's Disease and Fistula Initiated on Ustekinumab.

INTRODUCTION: Fistula is a common complication of Crohn's disease (CD). Treatment with biologics has been associated with fistula healing. Long-term persistence is an important factor for a chronic inflammatory process such as fistula. This study described 24-month persistence and time-to-surgery endpoints among bio-naïve patients with CD and intestinal fistula who were initiated on ustekinumab. METHODS: Adults with CD and any enteric or perianal fistula initiated on ustekinumab (index date) between September 23, 2016, and March 2, 2022, were selected from the IQVIA PharMetrics® Plus database and followed up to 24 months. Persistence on ustekinumab (no gaps in days of supply of > 120 days) and composite endpoints of being persistent while on monotherapy and persistent while corticosteroid free were also assessed. The date of surgery was defined as the date of first claim for any CD-related surgeries. Persistence and time-to-surgery endpoints were assessed from the index date until the earliest of discontinuation (event), immunomodulator or other biologic use (event), corticosteroid use (event), date of surgery (event), 24-month follow-up or data end (censoring) using Kaplan-Meier analyses. RESULTS: The sample included 445 patients (mean age: 42.8 years; 56.6% female). The most common type of fistula was anal fistula (36.0%). At 24 months after ustekinumab initiation, 64.2% of patients remained persistent (95% confidence interval [CI] 55.8-71.4). Furthermore, 53.3% of patients were persistent while on monotherapy (95% CI 45.1-60.7), and 45.6% of patients were persistent while being corticosteroid free (95% CI 36.9-53.8). At 24 months, 22.8% (95% CI 17.0-30.3) of patients underwent any CD-related surgery. CONCLUSION: This study quantified long-term persistence on ustekinumab among bio-naïve patients with CD and fistula. Over half of patients initiated on ustekinumab were persistent and persistent while on monotherapy 24 months after initiation. Time-to-surgery estimate was comparable to existing evidence. These findings support ustekinumab as a treatment option for long-term management of CD with fistula.

Visceral to subcutaneous fat area ratio predicts severe abdominal adhesions in definitive surgery for anastomotic fistula after small intestine resection.

Abdominal adhesions manifests following abdominal infections triggered by intestinal fistulas. The severity of such adhesions depends on the extent of fiber deposition and peritoneal fibrinolysis following peritoneal injury, which may be influenced by sustained inflammation within the abdominal cavity. In this regard, the visceral-to-subcutaneous fat area (VFA/SFA) ratio has been implicated as a potential marker of inflammation. This study aimed to explore the relationship between VFA/SFA and abdominal adhesions. This multicenter study was conducted across four tertiary institutions and involved patients who had undergone definitive surgery (DS) for intestinal fistula from January 2009 and October 2023. The presence of abdominal adhesions was determined intraoperatively. VFA/SFA was investigated as a potential risk factor for severe adhesions. The study comprised 414 patients with a median age of 50 [interquartile range (IQR) 35-66] years and a median body mass index of 20.0 (IQR 19.2-22.4) kg/m2, including 231 males with a median VFA/SFA of 1.0 (IQR 0.7-1.2) and 183 females a median VFA/SFA of 0.8 (0.6-1.1). VFA/SFA was associated with severe abdominal adhesions in males [odds ratio (OR) = 3.34, 95% CI 1.14-9.80, p = 0.03] and females (OR = 2.99, 95% CI 1.05-8.53, p = 0.04). J-shaped association between VFA/SFA ratio and severe adhesions was revealed in both sex. The increasing trend can be revealed when OR more than 0.8, and 0.6 in males and females respectively. Preoperative VFA/SFA demonstrates predictive value for statues of severe abdominal adhesions in DS for anastomotic fistula after small intestine resection.

Management of Complications in Crohn's Disease.

Complications of Crohn's disease reach far beyond postsurgical leak, infection, and enterocutaneous fistula. Malnutrition, intestinal failure, and recurrent disease all will require ongoing attentions. The management of these patients may further be complicated by the need for chronic immunosuppression. The underlying principles continue to include optimization of nutritional status, and preservation of bowel length when possible. However, there have been several recent advances in both the medical and surgical management of the disease. Understanding the contribution of the mesentery to inflammation, new surgical techniques such as the Kono-S anastomosis and extended mesenteric resection is decreasing the need for repeated resections.

Ruptured giant splenic artery aneurysm with an exceptional concurrent gastric and transverse colonic fistula: A rare case report.

INTRODUCTION: Splenic artery aneurysm (SAA) is a focal dilation of the splenic artery with varying etiologies including atherosclerosis, arteritis, or trauma. Giant SAAs with a diameter of 10 cm is rare and can lead to severe complications like rupture and fistulas. Therefore, an accurate and timely diagnosis and treatment are important. PATIENT CONCERNS: A 50-year-old male presented with acute epigastric pain and hemorrhagic shock. Considering his symptoms and examination, ultrasound, multi-slice computed tomography and digital subtraction angiography results, a ruptured giant splenic artery aneurysm complicated with an exceptional gastric and transverse colonic fistula was suspected. DIAGNOSIS: Ruptured giant splenic artery aneurysm. INTERVENTIONS: Left anterolateral thoracotomy to control the severe aortic bleeding just above the diaphragm, aneurysmectomy, splenectomy, and closing the gastric and transverse colon perforations. OUTCOMES: Multi-slice computed tomography demonstrated the presence of splenic artery aneurysm in the distal third measuring (10 × 12 cm) in diameter with a true lumen measuring (7 × 3.5 cm) and a large hematoma extending to the greater and lesser gastric curvature. Intraoperatively, a large pulsating mass was detected occupying the epigastrium and the left hypochondrium with severe adhesions with the stomach and transverse colon. CONCLUSION: Giant SAA with a diameter of 10 cm is rare and is associated with severe complications. Therefore, successful treatment of splenic artery aneurysms involves prompt diagnosis, immediate surgical intervention to control bleeding, and tailored approaches like thoracotomy to control the thoracic aorta for better hemodynamic stabilization, aiming to eliminate the aneurysm and reduce complications effectively.

Cholecystoappendiceal fistula associated with xanthogranulomatous cholecystitis.

Xanthogranulomatous cholecystitis is a rare chronic inflammatory disease of the gallbladder associated with complications such as perforation, dense adhesions and fistulation. We present a case of a female patient in her 20s who presented with three episodes of recurrent cholecystitis over 3 months. Her medical history included an endoscopic retrograde cholangiopancreatography for obstructive jaundice due to choledocholithiasis. As there was no possibility of performing an urgent cholecystectomy during her initial admission, she was listed for an elective operation. Laparoscopic inspection revealed a pericholecystic mass involving the omentum, transverse colon, duodenum and liver and findings suspicious of a cholecystoappendiceal fistula. Laparoscopic cholecystectomy and appendicectomy were performed. Early index admission laparoscopic cholecystectomy should be performed in patients with acute cholecystitis to prevent higher grades of operative difficulty and associated complications. This case presentation-cholecystoappendiceal fistula associated with xanthogranulomatous cholecystitis-emphasises the necessity of complying with national guidelines in managing acute calculous cholecystitis.

Colo-salpingeal fistula: a rare gynecologic manifestation of diverticular disease.

INTRODUCTION: Diverticulitis can be complicated by fistulas between the colon and neighboring structures, which predispose to significant morbidity and mortality. Fistulas involving the female urogenital tract often present with urogynecologic symptoms, such as vaginal discharge or recurrent urinary tract infections. While colo-vaginal fistulas, a more common variant, often present with vaginal flatulence, colo-salpingeal fistulas are exceedingly rare and have not been reported with this symptomatology. We describe a case of colo-saplingeal fistula presenting with vaginal flatulence, requiring multidisciplinary collaboration for diagnosis and management. CASE: A 63-year-old woman presented with vaginal flatulence in the setting of persistent diverticulitis. Computed tomography (CT) scan revealed sigmoid diverticulitis, a submucosal abscess abutting the uterus, and air within the endometrial cavity, raising suspicion for a colo-uterine fistula. Following transient symptomatic relief with medical management and antibiotics, recurrence of symptoms prompted surgical intervention. Laparoscopic exploration allowed diagnosis of the colo-salpingeal fistula. Sigmoid colectomy and left salpingo-oophorectomy were performed with a minimally invasive surgical approach, resulting in an uncomplicated recovery with remission of symptoms. DISCUSSION: This rare case highlights novel gynecologic symptoms for a colo-salpingeal fistula, contrasted with reported presentations through a comprehensive literature review. This case underscores the importance of recognizing gynecologic symptoms related to diverticular disease, which may be subtle, but provide important considerations for prognosis and treatment. A multidisciplinary approach to care from diagnosis through surgery allowed for successful recognition and minimally invasive treatment of this anomalous condition before further complications could arise. Ultimately, surgical approaches to diverticulitis-associated gynecologic fistulas should be individualized.

Laparoscopic Management of Gastrocolic Fistula in a Patient with a History of an Unusual Loop Gastric Bypass-a Video Vignette.

Gastrocolic fistula (GCF) is defined as an abnormal pathological communication between the epithelialized mucosal layers of the stomach and colon. In rare cases, complications following gastric bypass surgery, such as leakage or complicated marginal ulcers, may contribute to the development of a GCF. The laparoscopic approach for managing GCF involves a one-stage procedure that includes resection of the fistula and reconstruction of the gastrointestinal tract.

Outcomes of surgical treatment for enterovesical fistula in Crohn's disease.

Enterovesical fistula (EVF) in Crohn's disease (CD) often does not improve with medical treatment and requires surgical treatment. The surgical treatment strategy for EVF in CD is definitive resection of the intestinal tract side, and performing a leak test using dye injection into the bladder after EVF dissection to determine the appropriate surgical procedure for the bladder side. This study aimed to evaluate the outcomes of surgical treatment for EVF in CD. Twenty-one patients who underwent surgery for EVF between 2006 and 2021 were included and retrospectively evaluated for clinical background, surgical procedures, and postoperative complications. The most common origin of EVF was the ileum (17 cases; 81%), and the most common site of EVF formation was the apex (12; 57%). Surgical approaches were laparotomy in 11 (52%) cases and laparoscopy in 10 (48%). Surgical procedures on the bladder side were fistula dissection in 13 (62%) cases and sutured closure of fistula in 8 (38%). A comparison of approaches revealed no significant difference in operative time, but the amount of blood loss was significantly less in the laparoscopy (p < 0.01). There was no significant difference in the occurrence of postoperative complications between approaches. Postoperative anti-TNF-α antibody agents were used in 17 (81%) cases, and there were no cases of recurrent EVF. In conclusion, definitive resection of the intestinal tract and minimal treatment on the bladder side were sufficient to achieve satisfactory outcomes for EVF in CD.

An Asymptomatic Sigmoid Colonic Fistula Arising from a Large Aneurysm of the Internal Iliac Artery Was Discovered during a Medical Examination.

The rupture of an internal iliac artery aneurysm in the colon is a rare but potentially fatal complication. We report a rectal fistula of an asymptomatic internal iliac artery aneurysm that was discovered incidentally during a medical examination. A 77-year-old man presented at a local hospital for a general medical examination. Although the blood reports revealed severe anemia, the patient did not complain of any associated symptoms including dizziness and hematochezia. Moreover, there was no palpable mass in the patient's abdomen, and there was no evidence of hematochezia, as the patient had been using a bidet. Interestingly, computed tomography (CT) revealed a large right internal iliac artery aneurysm. There was a suspicious finding of a fistula within the colon in the CT, but it was undetected in the preoperative sigmoidoscopy. Furthermore, operative findings showed a protruding retroperitoneal mass adhering to the mesentery of the sigmoid colon. During aneurysm resection, the presence of a fistula was unclear. However, a fistula tract, devoid of any infectious bacteria such as tuberculosis, was found in the specimen after colon resection. After a recovery period of approximately one week, the patient was discharged from the hospital without any unusual findings on the post-operative CT. Sigmoid colonic fistulas arising from iliac artery aneurysms are rare. Also, diagnosis may be delayed in special circumstances wherein a patient routinely uses a bidet.

Retrospective study on the feasibility and safety of laparoscopic surgery for complicated fistulizing diverticular disease in a high-volume colorectal center.

BACKGROUND: We assessed feasibility and safety of laparoscopic sigmoidectomy for complicated fistulizing diverticular disease in a tertiary care colorectal center. METHODS: A single-center retrospective study of patients undergoing sigmoidectomy for fistulizing diverticular disease between 2011 and 2021 was realized. Primary outcomes were rates of conversion to open surgery and severe postoperative morbidity at 30 days. Secondary outcomes included rates of postoperative bladder leaks on cystogram. RESULTS: Among the 104 patients, 32.7% had previous laparotomy. Laparoscopy was the initial approach in 103 (99.0%), with 6 (5.8%) conversions to laparotomy. Clavien-Dindo grade ≥ III complication rate at 30 days was 10.6%, including two (1.9%) anastomotic leaks. The median postoperative length of stay was 4.0 days. Seven (6.7%) patients underwent reoperation, six (5.8%) were readmitted, and one (0.9%) died within 30 days. Twelve (11.5%) ileostomies were created initially, and two (1.9%) were created following anastomotic leaks. At last follow-up, 101 (97.1%) patients were stoma-free. Urgent surgeries had a higher rate of severe postoperative complications. Among colovesical fistula patients (n = 73), postoperative cystograms were performed in 56.2%, identifying two out of the three bladder leaks detected on closed suction drains. No differences in postoperative outcomes occurred between groups with and without postoperative cystograms, including Foley catheter removal within seven days (73.2% vs. 90.6%, p = 0.08). CONCLUSIONS: Laparoscopic surgery for complicated fistulizing diverticulitis showed low rates of severe complications, conversions to open surgery and permanent stomas in high-volume colorectal center.

A secondary abdominal aorta-duodenal fistula accompanied with acquired Immune Deficiency Syndrome presented with recurrent sepsis: a case report.

BACKGROUND: Abdominal aorta-duodenal fistulas are rare abnormal communications between the abdominal aorta and duodenum. Secondary abdominal aorta-duodenal fistulas often result from endovascular surgery for aneurysms and can present as severe late complications. CASE PRESENTATION: A 50-year-old male patient underwent endovascular reconstruction for an infrarenal abdominal aortic pseudoaneurysm. Prior to the operation, he was diagnosed with Acquired Immune Deficiency Syndrome and Syphilis. Two years later, he was readmitted with lower extremity pain and fever. Blood cultures grew Enterococcus faecium, Salmonella, and Streptococcus anginosus. Sepsis was successfully treated with comprehensive anti-infective therapy. He was readmitted 6 months later, with blood cultures growing Enterococcus faecium and Escherichia coli. Although computed tomography did not show contrast agent leakage, we suspected an abdominal aorta-duodenal fistula. Esophagogastroduodenoscopy confirmed this suspicion. The patient underwent in situ abdominal aortic repair and received long-term antibiotic therapy. He remained symptom-free during a year and a half of follow-up. CONCLUSIONS: This case suggests that recurrent infections with non-typhoidal Salmonella and gut bacteria may be an initial clue to secondary abdominal aorta-duodenal fistula.

Engineered Regenerative and Adhesive Hydrogel for Concurrent Sealing and Healing of Enterocutaneous Fistulas.

In addressing the intricate challenges of enterocutaneous fistula (ECF) treatment, such as internal bleeding, effluent leakage, inflammation, and infection, our research is dedicated to introducing a regenerative adhesive hydrogel that can seal and expedite the healing process. A double syringe setup was utilized, with dopagelatin and platelet-rich plasma (PRP) in one syringe and Laponite and sodium periodate in another. The hydrogel begins to cross-link immediately after passing through a mixing tip and exhibits tissue adhesive properties. Results demonstrated that PRP deposits within the pores of the cross-linked hydrogel and releases sustainably, enhancing its regenerative capabilities. The addition of PRP further improved the mechanical properties and slowed down the degradation of the hydrogel. Furthermore, the hydrogel demonstrated cytocompatibility, hemostatic properties, and time-dependent macrophage M1 to M2 phase transition, suggesting the anti-inflammatory response of the material. In an in vitro bench test simulating high-pressure fistula conditions, the hydrogel effectively occluded pressures up to 300 mmHg. In conclusion, this innovative hydrogel holds promise for ECF treatment and diverse fistula cases, marking a significant advancement in its therapeutic approaches.

The potential for medical therapies to address fistulizing Crohn's disease: a state-of-the-art review.

INTRODUCTION: Crohn's disease (CD) is a chronic, relapsing immune mediated disease, which is one of the two major types of inflammatory bowel disease (IBD). Fistulizing CD poses a significant clinical challenge for physicians. Effective management of CD requires a multidisciplinary approach, involving a gastroenterologist and a GI surgeon while tailoring treatment to each patient's unique risk factors, clinical representations, and preferences. AREAS COVERED: This comprehensive review explores the intricacies of fistulizing CD including its manifestations, types, impact on quality of life, management strategies, and novel therapies under investigation. EXPERT OPINION: Antibiotics are often used as first-line therapy to treat symptoms. Biologics that selectively target TNF-α, such infliximab (IFX), have shown high efficacy in randomized controlled trials. However, more than 50% of patients lose response to IFX, prompting them to explore alternative strategies. Current options include adalimumab and certolizumab pegol combination therapies, as well as small-molecule drugs targeting Janus kinases such as Upadacitinib. Furthermore, a promising treatment for complex fistulas is mesenchymal stem cells such as Darvadstrocel (Alofisel), an allogeneic stem cell-based therapy. However, surgical interventions are necessary for complex cases or intra-abdominal complications. Setons and LIFT procedures are the most common surgical options.

Clinical trial: The effectiveness of long-acting somatostatin analogue for output reduction of high-output intestinal fistula or small bowel enterostomy. A randomised controlled trial.

BACKGROUND: High-output intestinal fistulas and small bowel enterostomies are associated with morbidity and mortality. Current standard treatment for output reduction consists of fluid and dietary restrictions and medical therapy. There is conflicting evidence regarding the use of somatostatin analogues for output reduction. AIM: The aim of this study is to investigate whether lanreotide, added to current standard treatment, further reduces intestinal output in patients with high-output fistulas and enterostomies. METHODS: This was an open-label, multicentre, randomised controlled trial. Adult patients with a high-output intestinal fistula (>500 mL/24 h) or small bowel enterostomy (>1500 mL/24 h) more than 4 weeks post-surgery and receiving standard medical treatment (dietary- and fluid restriction, PPI, loperamide and codeine) for at least 2 weeks were eligible for inclusion. We randomised patients 1:1 between continuing standard treatment (control), and subcutaneous lanreotide 120 mg every 4 weeks with standard treatment. The primary outcome was the number of responders, with response defined as an output reduction of ≥25%, 8 weeks after randomisation. We also investigated the proportional change in output. RESULTS: We randomised 40 patients; 17 had a fistula and 23 a small bowel enterostomy. There were 9/20 responders in the intervention group and 2/20 in the control group (p = 0.013). The proportional output reduction was -26% (IQR -4 to -38) in the intervention group, compared to an increase of 4% (IQR 20 to -13) in the control group (p = 0.004). CONCLUSIONS: In patients with a high-output fistula or small bowel enterostomy, addition of lanreotide to current standard treatment can provide a clinically relevant output reduction. TRIAL REGISTRATION: EudraCT: 2013-003998-10.

Primary Aortoenteric Fistula Due to Salmonella typhi-related Mycotic Aneurysm.

Primary aortoenteric fistulas (AEF) are rare. The majority of these are due to atherosclerotic aortic aneurysms. Mycotic aortic aneurysms leading to primary AEF are exceedingly uncommon. Here we report a rare case of primary AEF secondary to Salmonella-related mycotic aneurysm and discuss the diagnostic and therapeutic issues.