Periscope sandwich stenting as an alternative to open cervical revascularization of left subclavian artery during zone 2 thoracic endovascular aortic repair.

OBJECTIVE: Revascularization of the left subclavian artery (LSA) during zone 2 thoracic endovascular aortic repair (TEVAR) maintains collateral circulation to decrease ischemic complications, including stroke, spinal cord ischemia, and upper extremity ischemia. Both open surgical and endovascular LSA revascularization techniques have been described, each with unique risks and benefits. We describe our "periscope sandwich" technique for the LSA during zone 2 TEVAR, which maintains antegrade access to the distal abdominal aorta if subsequent interventions are necessary. Technical results and short-term outcomes are compared with LSA open surgical debranching. METHODS: A single-institution retrospective review was performed for patients requiring zone 2 TEVAR with LSA revascularization by periscope sandwich technique or open surgical debranching with subclavian to carotid transposition (SCT) or carotid-subclavian bypass (CSB). The presenting aortic disease and perioperative details were recorded. Intraoperative angiography and postoperative computed tomography images were reviewed for occurrence of endoleak and branch patency. RESULTS: Between January 2013 and December 2018, the LSA was revascularized by periscope sandwich in 18 patients, SCT in 22 patients, and CSB in 13 patients. Compared with open surgical debranching, periscope sandwich had a lower median estimated blood loss (100 mL vs 200 mL for pooled SCT and CSB; P = .03) and lower median case duration (133.5 minutes vs 226 minutes; P < .001). Contrast material volume (120 mL vs 120 mL; P = .98) and fluoroscopy time (13.1 minutes vs 13.3 minutes; P = .92) did not differ significantly between the groups. There was no difference in aorta-related mortality (P = .14), and LSA patency was 100%. Median follow-up for the periscope sandwich group was 11 months, with an overall estimated 91% freedom from gutter leak at 6 months. CONCLUSIONS: LSA periscope sandwich technique provides safe and effective LSA revascularization during zone 2 TEVAR. LSA periscope sandwich can be used emergently with off-the-shelf endovascular components and facilitates future branched-fenestrated endovascular repair of thoracoabdominal aortic diseases.

Atypical Presentation of a Marjolin Ulcer After a Burn: A Case Report.

The development of a nonhealing ulcer on a chronic wound or scar should raise suspicions of the plastic surgeon or nurse regarding the potential for malignant degeneration to a Marjolin ulcer. Occasionally, a Marjolin ulcer may present as exophytic granulation tissue within a scar. Most Marjolin ulcers are well-differentiated injuries; however, because of their aggressive nature and poor prognosis, to ensure surgical success, diagnosis of Marjolin ulcer should be confirmed and treatment initiated as soon as possible.

Complications and Impact on Quality of Life of Vertical Rectus Abdominis Myocutaneous Flaps for Reconstruction in Pelvic Exenteration Surgery.

BACKGROUND: Pelvic exenteration for malignancy sometimes necessitates flap reconstruction. OBJECTIVE: This study's aim was to investigate flap-related morbidity. DESIGN: A prospective database was reviewed from 2003 to 2016. All medical charts, correspondence, and outpatient follow-up records up to May 2017 were reviewed. SETTINGS: This study was conducted at a tertiary referral unit. PATIENTS: Patients who underwent pelvic exenteration surgery were selected. INTERVENTIONS: Reconstruction was performed with a vertical rectus abdominis myocutaneous flap. MAIN OUTCOME MEASURES: Primary outcome was flap-related complications (short or long term >3 months). Secondary outcomes were hospital stay, readmission, mortality, and quality of life (Short Form-36, Functional Assessment of Cancer Therapy for patients with colorectal cancer). RESULTS: Of 519 patients undergoing pelvic exenteration surgery, 87 (17%) underwent flap reconstruction. Median follow-up was 20 months (interquartile range, 8-39 months). Median age was 60 years (interquartile range, 51-66). Flap-related complications were found in 59 patients (68%), with minor recipient-site complications diagnosed in 33 patients (38%). In the short term, 15 patients experienced major recipient-site complications (17%), including flap separation (n = 7) and partial (n = 3) or complete necrosis (n = 4). Flap removal was required in 1 patient. Obesity was the single independent risk factor for short-term flap-related complications (p = 0.02). Hospital admission was significantly longer in patients with short-term major flap complications (median 65 days, p < 0.001) compared with patients without or with minor complications. There was no 90-day mortality. Patients who required flap reconstruction reported lower baseline quality-of-life scores than patients without flap reconstruction, but both recovered over time. In the long term, minor flap-related complications occurred in 12 patients, and 11 patients had major donor-site complications. Fourteen patients developed major recipient-site complications (16%), including sacral collections, enterocutaneous fistulas, perineal ulcer, or hernia. LIMITATIONS: This was a retrospective analysis of prospectively collected data. CONCLUSIONS: Vertical rectus abdominis myocutaneous flaps in pelvic exenteration surgery have a high incidence of morbidity that has significant impact on hospital stay and a temporary impact on quality of life. Flap reconstruction should be used selectively in pelvic exenteration surgery. See Video Abstract at http://links.lww.com/DCR/B274. COMPLICACIONES E IMPACTO EN LA CALIDAD DE VIDA DE LOS COLGAJOS MIOCUTÁNEOS DE MUSCULO RECTO DEL ABDOMEN EN CASOS DE RECONSTRUCCIÓN DE EXENTERACIÓN PÉLVICA: La exenteración pélvica (EP) para malignidad a veces requiere reconstrucción con colgajos musculares.El propósito del presente estudio fue investigar la morbilidad relacionada con los colagajos musculares.Revisión de una base de datos prospectiva de 2003-2016. Se evaluaron todas las historias clínicas, la correspondencia y los registros de seguimiento de pacientes ambulatorios hasta mayo de 2017.Unidad de referencia terciaria.Todos aquellas personas con cirugía de exenteración pélvica.Reconstrucción con colgajo miocutáneo de musculo recto vertical del abdomen.El resultado primario fueron las complicaciones relacionadas con el colgajo (a corto o largo plazo >3 meses). Los resultados secundarios fueron la estadía hospitalaria, la readmisión, la mortalidad y la calidad de vida (QOL; SF-36, FACT-C).De 519 pacientes sometidos a EP, 87 (17%) se sometieron a reconstrucción con colgajos miocutáneos. La mediana de seguimiento fue de 20 meses (RIC 8-39 meses). La mediana de edad fue de 60 años (IQR 51-66). Se encontraron complicaciones relacionadas con el colgajo en 59 pacientes (68%), con complicaciones menores en el sitio del receptor diagnosticadas en 33 pacientes (38%). A corto plazo, quince pacientes sufrieron complicaciones mayores en el sitio del receptor (17%), incluida la separación del colgajo (n = 7), necrosis parcial (n = 3) o necrosis completa (n = 4). Se requirió la extracción del colgajo en un paciente. La obesidad fue el único factor de riesgo independiente para complicaciones relacionadas con el colgajo a corto plazo (p = 0.02). El ingreso hospitalario fue significativamente mayor en pacientes con complicaciones de colgajos mayores a corto plazo (mediana 65 días p <0.001) en comparación con pacientes sin complicaciones menores o con complicaciones menores. No hubo mortalidad a los 90 días. Los pacientes que requirieron reconstrucción con colgajo informaron puntajes de calidad de vida basales más bajos que los pacientes sin reconstrucción con colgajo, pero ambos se recuperaron con el tiempo. A largo plazo, ocurrieron complicaciones menores relacionadas con el colgajo en 12 pacientes y 11 pacientes tuvieron complicaciones mayores en el sitio donante. Catorce pacientes desarrollaron complicaciones mayores en el sitio del receptor (16%), incluidas colecciones sacras, fístulas enterocutáneas, úlceras perineales o herniación.Análisis retrospectivo de datos recolectados prospectivamente.Los colgajos miocutáneos del musculo recto vertical del abdomen en casos de cirugía de exenteración pélvica tienen una alta incidencia de morbilidad conllevando a un impacto significativo en la estadía hospitalaria y un impacto temporal en la calidad de vida. Las reconstrucciones con colgajos deben aplicarse muy selectivamente en la cirugía de exenteración pélvica. Consulte Video Resumen en http://links.lww.com/DCR/B274.

[An 84-year-old man with an ulcer on his ankle]. / Een 84-jarige man met een ulcus op zijn enkel.

Hydroxycarbamide is a cytotoxic drug that is used in haematological cancers. On long-term use (2-15 years) of 1500-2000 mg a day, there is a 9% risk of developing ulcers. This patient's ulcer was painful, of punched out aspect, with a necrotic base and swollen wound edges. Upon discontinuation of hydroxycarbamide, the wound healed within 2 months.

Proteomics Highlights Common and Distinct Pathophysiological Processes Associated with Ileal and Colonic Ulcers in Crohn's Disease.

BACKGROUND AND AIMS: Based on genetics and natural history, Crohn's disease can be separated into two entities, an ileal and a colonic disease. Protein-based approaches are needed to elucidate whether such subphenotypes are related to distinct pathophysiological processes. METHODS: The proteome of ulcer edges was compared with that of paired control tissue samples [n = 32 biopsies] by differential proteomics in the ileum and the colon of Crohn's disease patients [n = 16]. The results were analysed using a hypothesis-driven approach [based on the literature] and a hypothesis-free approach [pathway enrichment analyses] to determine common and segment-specific pathophysiological processes associated with ileal and colonic CD ulcer edges. To confirm the involvement of a key pathway highlighted by proteomics, two proteins were also studied by immunochemistry. RESULTS: In the ileum and the colon, 4428 and 5204 proteins, respectively, were identified and quantified. Ileal and colonic ulcer edges differed in having a distinct distribution of proteins associated with epithelial-mesenchymal transition, neutrophil degranulation, and ribosomes. Ileal and colonic ulcer edges were similarly characterized by an increase in the proteins implicated in the endoplasmic reticulum protein-processing pathway and a decrease in mitochondrial proteins. Immunochemistry confirmed the presence of endoplasmic reticulum stress in the mucosa of ileal and colonic ulcer edges. CONCLUSION: This study provides protein-based evidence for partially distinct pathophysiological processes being associated with ileal and colonic ulcer edges in Crohn's disease patients. This could constitute a first step toward the development of gut segment-specific diagnostic markers and therapeutics.

Congenital insensitivity to pain with anhidrosis syndrome: A series from Jordan.

OBJECTIVES: To present the clinical picture, the associated complications and the genetic findings of Jordanian patients diagnosed with Congenital insensitivity to pain with anhidrosis (CIPA). PATIENTS AND METHODS: This is a retrospective study including 7 patients diagnosed with CIPA presenting to Jordan University Hospital neurology clinic between 2001 and 2017. RESULTS: Among five families, seven patients were diagnose with CIPA and followed for a period ranging from one month to 6 years. The initial symptom observed in all patients was high fever in the first few days after birth, decreased sensation to pain and decreased sweating were later noted. Poor weight gain, microcephaly and global developmental delay were present in most cases. All patients had tongue ulcerations. Fingers/toes ulcerations were present in 6/7 (86.0 %), hip joint dislocation in 3/7 (43.0 %), chronic arthritis and joint swelling in 6/7 (86.0 %), corneal ulcers in 4/7 (57.1 %) and kidney amyloidosis in 1/7 (13.0 %) of all patients. Death occurred in 4/7 (57.1 %) patients. Consanguinity was present in all families. Mutation analysis revealed three variants in NTRK1 gene. The frameshift (c.1860_1861insT; p.Pro621fs) mutation was common in our series. One patient carried a novel missense mutation (c.2170 G > A; p.Gly724Ser). The third missense mutation (C2125 G > T; p.Val709Leu) was reported in a previous study in one patient. CONCLUSION: This cohort reveals a severe CIPA phenotype necessitating thorough multidisciplinary care and follow up.

Atypical Ulcers: Diagnosis and Management.

Atypical ulcers show atypical clinical features, histology, localization, and resistance to standard therapies. The persistence of a chronic ulcer despite treatment with standard therapies requires a more specific diagnostic investigation. Diagnosis involves obtaining the history and performing clinical examination and additional tests. A skin biopsy is frequently used to confirm unclear diagnosis. In difficult cases, microbiological and immunohistochemical examinations, laboratory blood tests, or instrumental tests should be evaluated. The treatment of atypical wounds is characterized by local systemic therapy and pain control. Our results highlight the need for early diagnosis, and standardized and targeted management by a multidisciplinary wound healing center.

A Single Center Experience of In Situ Needle Fenestration of Supra-aortic Branches During Thoracic Endovascular Aortic Repair.

BACKGROUND: To report the early results and technical details of in situ needle fenestration during thoracic endovascular aortic repair (TEVAR). MATERIALS AND METHODS: Thirty-seven patients with thoracic aortic disease who underwent TEVAR with in situ needle fenestration in our department between February 2016 and April 2017 were included in this study. Their demographic information, clinical manifestations, periprocedural outcomes, and follow-up results were analyzed. RESULTS: In total, 96.4% of attempted fenestrations were successful (53/55). Fenestration of the left subclavian artery (LSA) was performed in 26 patients, fenestration of either the LSA or brachiocephalic trunk (BCT) plus the left common carotid artery (LCCA) was performed in six patients, and fenestration of the three supra-aortic branches was performed in five patients. In the three-fenestration group with five patients, the procedure was under the protection of a cardiopulmonary bypass. External iliac artery rupture occurred in one case. Cerebrovascular events occurred in three cases, and myocardial infarction occurred in one. One case had a branch stent graft stuck in the brachial artery. During a median follow-up of 21 months, two patients developed retrograde type A dissection, and one was subsequently treated with a stent graft and BCT fenestration. One case presented with numbness in the fingertips of the left hand, and computed tomography angiography (CTA) indicated stenosis of the branch stent in the LSA. CTA examination revealed no endoleaks or expansion of the aortic aneurysms in any of the patients. CONCLUSIONS: In situ needle fenestration of endografts in the aortic arch is technically feasible, yielding acceptable short-term results in a selected patient cohort. Further studies are needed to determine mid- and long-term outcomes before more widespread adoption.

Unconventional Endovascular Access for Symptomatic Thoracic Aortic Ulcer with Infrarenal Aortic Occlusion-A Case Report.

BACKGROUND: A man in very poor general condition was admitted for acute thrombosis of the infrarenal aorta associated to a penetrating aortic ulcer (PAU) of the distal thoracic aorta. METHODS: We planned a two-stage procedure: an axillobifemoral revascularization to be followed by thoracic endovascular aortic repair (TEVAR) after rehabilitation. Before the second stage, the patient presented with acute respiratory failure secondary to an abrupt PAU evolution. RESULTS: A properly selected stent graft was successfully deployed in an antegrade manner through a left axillary artery access with the nose of the delivery system pushed over a guidewire deep into the aortic thrombosis. CONCLUSIONS: Inadequate access and paraplegia are the major challenges hampering clinical success of TEVAR. Off-the-shelf stent graft can be used outside its primary use in an unconventional setting. Careful planning, consideration of all comorbidities and vascular anatomy, as well as correct choice of the device are crucial for the successful treatment.

In Vivo Assessment of Ascending and Arch Aortic Compliance.

BACKGROUND: Dynamic compliance (Cd) of the adult thoracic ascending and arch aorta has had limited in vivo evaluation in patients with aortic disease. This study evaluates aortic compliance using intravascular ultrasound (IVUS) across a range of thoracic aortic diseases. METHODS: Seventy-nine patients undergoing thoracic aortic endovascular procedures had Cd measurements of the ascending aorta proximal to the origin of the brachiocephalic trunk and distal to the origin of the left common carotid artery using IVUS before endograft deployment. Cd was calculated for each segment using the following equation, Cd = ΔD/(D • ΔP) where ΔD = change in aortic diameter, D = diameter in diastole, and ΔP = pulse pressure. RESULTS: Mean Cd of the ascending aorta in all patients (18.4%/mm Hg) and aortic arch (16.5 %/100 mm Hg) did not differ significantly. Compliance was significantly lower in patients being treated for thoracic aortic aneurysm and penetrating ulcer than in patients with traumatic rupture, acute and chronic dissection (P = 0.009). Compliance was significantly higher in patients with aortic transection compared with thoracic aneurysm or penetrating ulcer (P = 0.001). Compliance decreased with age by 0.44 ± 0.06 (P = 0.001) per year in the ascending aorta and 0.41 ± 0.05 (P = 0.001) per year in the aortic arch. Compliance did not increase with diameter when adjusted for age (P = 0.65). Compliance measured in the ascending aorta in 7 patients after descending thoracic aortic endograft repair decreased to 12.6%/100 mm Hg, although not significant (P = 0.18). CONCLUSIONS: Ascending and aortic arch compliance is significantly higher than reported for peripheral vessels. Thoracic aortic compliance decreases with age and is not related to aortic diameter. The results of the present study are important when considering the development of endoprosthesis devices and long-term effects on the thoracic aorta.

Endovascular Repair of a Penetrating Aortic Ulcer with a Custom-made Relay Stent Graft Featuring a Single Celiac Trunk Fenestration and a Superior Mesenteric Artery Scallop.

We report the case of a 70-year-old man with an asymptomatic, fast-growing, paraceliac penetrating aortic ulcer (PAU). Guidelines recommend endovascular repair if an asymptomatic PAU shows a mean growth rate ≥5 mm per year: this patient's maximum aortic diameter was 47 mm but had increased 10 mm in the previous year. The very short sealing zones required a custom-made stent graft. A custom-made relay stent graft comprises a single celiac trunk fenestration, a superior mesenteric artery (SMA) scallop measured according to SMA ostium size, an uncovered distal stent, and 6-mm tapering was used with technical and clinical success.

Redefining the histopathologic profile of acute aortic syndromes: Clinical and prognostic implications.

OBJECTIVES: The study objectives were to describe the aortic histopathologic substrates in patients with type A surgically treated acute aortic syndromes, to provide clinico-pathological correlations, and to identify the possible prognostic role of histology. METHODS: We assessed the aortic wall degenerative or inflammatory alterations of 158 patients according to the histopathologic consensus documents. Moreover, we correlated these histologic patterns with the patients' clinical data and long-term follow-up for mortality, major aorta-related events, and nonaorta-related events (including cardiovascular ones). RESULTS: We identified 2 histopathologic patterns: 122 patients (77%) with degenerative alterations and 36 patients (23%) with mixed degenerative-atherosclerotic lesions. Patients with mixed alterations were older (mean 69.6 ± 8.7 years vs 62.2 ± 12.4 years, P = .001) and more hypercholesterolemic (33.3% vs 13.9%, P = .017). The degenerative subgroup showed more intralamellar-mucoid extracellular matrix accumulation (86% vs 66.7%, P = .017) and a lower prevalence of translamellar collagen increase (9.8% vs 50%, P < .001). Patients with mixed degenerative-atherosclerotic abnormalities more frequently had long-term nonaorta-related events compared with those with degenerative abnormalities alone (P = .046); no differences were found between the groups with respect to mortality, major aorta-related events, and cardiovascular nonaorta-related events. CONCLUSIONS: Although degenerative lesions of the medial layer were present in all specimens, substantial atherosclerosis coexisted in approximately one quarter of cases. Patients with mixed degenerative-atherosclerotic abnormalities had a coherent clinical risk profile, a clinical presentation frequently mimicking acute coronary syndrome, and a higher incidence of nonaorta-related events during follow-up. Histopathologic characterization may improve the long-term prognostic stratification of patients after surgical treatment.

Cyclodextrin Enhances Corneal Tolerability and Reduces Ocular Toxicity Caused by Diclofenac.

With advances in refractive surgery and demand for cataract removal and lens replacement, the ocular use of nonsteroidal anti-inflammatory drugs (NSAIDs) has increased. One of the most commonly used NSAIDs is diclofenac (Diclo). In this study, cyclodextrins (CDs), α-, ß-, γ-, and HP-ß-CDs, were investigated with in vitro irritation and in vivo ulceration models in rabbits to reduce Diclo toxicity. Diclo-, α-, ß-, γ-, and HP-ß-CD inclusion complexes were prepared and characterized and Diclo-CD complexes were evaluated for corneal permeation, red blood cell (RBCs) haemolysis, corneal opacity/permeability, and toxicity. Guest- (Diclo-) host (CD) solid inclusion complexes were formed only with ß-, γ-, and HP-ß-CDs. Amphipathic properties for Diclo were recorded and this surfactant-like functionality might contribute to the unwanted effects of Diclo on the surface of the eye. Contact angle and spreading coefficients were used to assess Diclo-CDs in solution. Reduction of ocular toxicity 3-fold to16-fold and comparable corneal permeability to free Diclo were recorded only with Diclo-γ-CD and Diclo-HP-ß-CD complexes. These two complexes showed faster healing rates without scar formation compared with exposure to the Diclo solution and to untreated groups. This study also highlighted that Diclo-γ-CD and Diclo-HP-ß-CD demonstrated fast healing without scar formation.

Anatomical predisposing factors of transmural thermal injury after pulmonary vein isolation.

Aims: Transmural thermal injury (TTI), such as oesophageal erosion/ulcer and perioesophageal nerve injury leading to gastric hypomotility, is an important complication associated with pulmonary vein isolation (PVI). However, a predictor of TTI concerning anatomical structures surrounding the oesophagus has not yet been fully elucidated. Therefore, we sought to identify the predisposing factors of TTI after PVI. Methods and results: Consecutive 110 patients, who underwent PVI for atrial fibrillation, received oesophagogastroduodenoscopy 2 days later, were investigated. The relationships between TTI and clinical and anatomical parameters were examined. Based on the computed tomography data, we measured the angle of the left atrial (LA) posterior wall to the descending aorta (Ao) (LA-Ao angle), the branching angle of the left inferior pulmonary vein (LIPV) to the coronal plane (LIPV angle), and the minimum distance between the LA posterior wall and descending Ao enclosing the oesophagus (LA-Ao distance). Transmural thermal injuries occurred in 21 patients (oesophageal erosion in 5 and gastric hypomotility in 16). Age, gender, body mass index, LA diameter, and LA volume index in echocardiography were not associated with TTI. However, the LIPV angle was larger and the LA-Ao distance was shorter in the TTI (+) group compared to the TTI (-) group. With multivariate logistic regression analysis, the LIPV angle [odds ratio (OR): 2.144, P = 0.0031] and LA-Ao distance (OR: 0.392, P = 0.0229) were independent predictors of TTI. Conclusion: The anatomical proximities of the LA posterior wall, LIPV, and descending Ao surrounding the oesophagus are strongly associated with the prevalence of TTI.

Diabetic ulcer regeneration: stem cells, biomaterials, growth factors.

The impairment of ulcer wound healing in diabetic patients is a vital clinical problem affecting millions of patients. Several clinical and basic science studies have demonstrated that stem cell therapy, to be effective in healing diabetic ulcer. Furthermore, these ulcer wounds may be healed from molecular maneuvering of growth factors to improve microcirculation within the ulcer wound. In addition, ulcer wound dressings may be employed as medicated systems, through the delivery of drugs, growth factors, peptides and stem cells. These dressing materials can include natural, modified and synthetic polymers, as well as their mixtures or combinations. This review paper will give a summary of some of the recent advances on the application of stem cells, biomaterials and growth factors in the treatment of diabetic ulcer wound.

Corrupted Colonic Crypts Bordering Regenerating Mucosal Ulcers in Ulcerative Colitis.

BACKGROUND/AIM: Histology in protracted ulcerative colitis (UC) discloses high numbers of chronic inflammatory cells and crypts with architectural distortions. In severe cases, ulcerations are frequently found. The histogenesis of colonic crypts with architectural distortions in UC remains elusive. A recent review of colectomy specimens from patients with UC revealed crypts surrounding mucosal ulcerations exhibiting severe architectural distortions. They were called corrupted colonic crypts, CCCs. MATERIAL AND METHODS: Archival hematoxylin and eosin (H&E)-stained sections from three colectomies having several mucosal ulcers were selected for the study. The mucosa bordering mucosal ulcers was particularly scrutinized. RESULTS: The review of 49 sections (mean=16.3, range=14-20) in the three colectomies revealed 60 ulcers (mean=20, range=13-27). The following CCC phenotypes were found bordering mucosal ulcers: with asymmetric lateral fission (n=11), with dual or three-foiled corrupted fission (n=19), with cystic dilatations (n=3), L-shaped crypts (n=7), T-inverted crypts (n=6), shoe-shaped crypts (n=3), horizontal crypts (n=14), multi-lobate crypts (n=2), and/or inter-connecting crypts (n=5). CONCLUSION: The regeneration of ulcers in UC seems to proceed with neo-formation of corrupted crypts. In the same colectomies, none to occasional CCCs were found in large areas of the mucosa having severe chronic inflammation. Importantly, none of the occasional CCCs were found in other diseases of the colonic mucosa with chronic inflammation or in unspecific ulcers of the colon. Since neither chronic mucosal inflammation per se, nor unspecific ulcers of the colon are central for the formation of CCCs, it is suggested that crypt distortions of the non-ulcerated colonic mucosa in patients with UC might mirror formerly healed mucosal ulcerations.