Perianal fistulizing Crohn's disease (PFCD)-associated anorectal and fistula cancers are rare but often devastating diagnoses. However, given the low incidence and consequent lack of data and clinical trials in the field, there is little to no guidance on screening and management of these cancers. To inform clinical practice, we developed consensus guidelines on PFCD-associated anorectal and fistula cancers by multidisciplinary experts from the international TOpClass consortium.

We conducted a systematic review by standard methodology, using the Newcastle-Ottawa Scale quality assessment tool. We subsequently developed consensus statements using a Delphi consensus approach.

Of 561 articles identified, 110 were eligible, and 76 articles were included. The overall quality of evidence was low. The TOpClass consortium reached consensus on 6 structured statements addressing screening, risk assessment, and management of PFCD-associated anorectal and fistula cancers. Patients with long-standing (>10 years) PFCD should be considered at small but increased risk of developing perianal cancer, including squamous cell carcinoma of the anus and anorectal carcinoma. Risk factors for squamous cell carcinoma of the anus, notably human papilloma virus, should be considered. New, refractory, or progressive perianal symptoms should prompt evaluation for fistula cancer. There was no consensus on timing or frequency of screening in patients with asymptomatic perianal fistula. Multiple modalities may be required for diagnosis, including an examination under anesthesia with biopsy. Multidisciplinary team efforts were deemed central to the management of fistula cancers.

Inflammatory bowel disease clinicians should be aware of the risk of PFCD-associated anorectal and fistula cancers in all patients with PFCD. The TOpClass consortium consensus statements outlined herein offer guidance in managing this challenging scenario.

Mucinous adenocarcinoma of anus is an uncommon neoplasm of the gastrointestinal tract. In most of the cases, early diagnosis of this disease is difficult since its symptoms frequently mimic benign inflammatory conditions.

A systematic PubMed and Scopus search was conducted, a propos of a case report.

One hundred fifty patients from 93 case reports were included. The mean age of the patients was 60.5 years (range: 18-81). The majority of them were males (124 out of 150, 82.7%), while the main known risk factor was the history of chronic fistula (109 out of 150, 72.7%). Recurrent perianal sepsis and perianal pain were the principal symptoms at the time of presentation. No symptoms have been reported only in three patients (3 out of 150, 2%). Regarding the prior surgical history of the patients, multiple abscess drainage and perianal fistula's related interventions were present in 62 (41.3%) and 19 (12.7%) patients, respectively. Neoadjuvant chemoradiotherapy was administered in 53 out of 150 patients (35.3%), while the majority of them have been treated with combined treatment of chemotherapy and radiotherapy. APR and its variations were the most applied surgical treatment (68%). Adjuvant chemoradiotherapy was administered almost up to one-third of the included patients (34%). Recurrence of the disease was reported in 41 out of 150 patients (27.3%). Death was reported in 44 out of 150 patients (29.3%).

Review of the available published literature suggests that perianal mucinous adenocarcinoma is an extremely rare neoplasia. Τhere is no consensus as far as the diagnosis and the treatment strategies, due to the rarity of this neoplasm. High degree of clinical suspicion as well as histopathological confirmation is the principal requisites for the diagnosis of mucinous adenocarcinoma, especially in the ground of chronic ulcero-proliferative perianal lesions.

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.

Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) that frequently affects the small bowel. Individuals diagnosed with CD are at increased risk of developing bowel cancer compared to the general population. Small bowel cancer is a rare but significant CD complication. Adenocarcinoma represents the most prevalent of these neoplasms, followed by neuroendocrine tumors and sarcomas. The primary risk factors identified are being of the male sex, disease duration, previous surgical intervention, perianal disease, and chronic inflammation. The precise etiology remains unclear. Another crucial issue concerns the role of immunomodulators and advanced therapies. By inhibiting inflammation, these therapies can reduce the risk of cancer, which is often initiated by the inflammation-dysplasia-adenocarcinoma sequence. In accordance with the most recent guidelines, it is not necessary to conduct surveillance in patients with small bowel cancer among CD patients, as it is considered a rare disease. Nevertheless, it is of significant importance for gastroenterologists to be aware of this potential CD complication, as well as the patients who are most at risk of developing it. The purpose of this review is to provide a comprehensive overview of CD-SBC, focusing on epidemiology, etiopathogenesis, risk factors, diagnosis, and the role of advanced therapies in CD-SBC.

Fistula formation is a major complication in Crohn's disease [CD] and the role of the immune cell compartment remains to be elucidated. Thus, we compared the immune cell compartment of CD fistula to inflammatory CD colitis using imaging mass cytometry [IMC] and immunofluorescence.

A 36-marker panel including structural, functional, and lineage markers for use in IMC was established. This panel was applied to analyse paraffin-embedded CD fistula tract [n = 11], CD colitis [n = 10], and colon samples from non-inflamed controls [n = 12]. Computational methods for cell segmentation, dimensionality reduction, and cell type clustering were used to define cell populations for cell frequency, marker distribution, and spatial neighbourhood analysis. Multiplex immunofluorescence was used for higher resolution spatial analysis.

Analysis of cell frequencies in CD fistulas compared to CD colitis and control colonic samples revealed a significant increase in neutrophils, effector cytotoxic T cells, and inflammatory macrophages in CD fistula samples, whereas regulatory T cells were decreased. Neutrophils in CD fistula expressed significantly more matrix metalloproteinase 9 [MMP9], correlating with extracellular matrix remodelling. Neighbourhood analysis revealed a strong association between MMP9+ neutrophils and effector cytotoxic T cells in both CD fistulas and colitis.

This study presents the first highly multiplexed single cell analysis of the immune cell compartment of CD fistulas and their spatial context. It links immune cell dynamics, particularly MMP9+ neutrophils, to extracellular matrix remodelling in CD fistulas, offering insights into the complex network of cellular interactions and potential therapeutic targets for CD complications.

The perianal disease affects up to one-third of individuals with Crohn's disease (CD), causing disabling symptoms and significant impairment in quality of life, particularly for those with perianal fistulising CD (PFCD). The collaborative effort between gastroenterologists and surgeons is essential for addressing PFCD to achieve fistula closure and promote luminal healing. Limited fistula healing rates with conventional therapies have prompted the emergence of new biological agents, endoscopic procedures and surgical techniques that show promising results. Among these, mesenchymal stem cells injection is a particularly hopeful therapy. In addition to the burden of fistulas, individuals with perianal CD may face an increased risk of developing anal cancer. This underscores the importance of surveillance programmes and timely interventions to prevent late diagnoses and poor outcomes. Currently, there is no established formal anal screening programme. In this review, we provide an overview of the current state of the art in managing PFCD, including novel medical, endoscopic and surgical approaches. The discussion also focuses on the relevance of establishing an anal cancer screening programme in CD, intending to propose a risk-based surveillance algorithm. The validation of this surveillance programme would be a significant step forward in improving patient care and outcomes.

Crohn's disease (CD)-associated intestinal cancers are characterized by their high incidence, particularly at the anorectal site in the Japanese population. Accumulating evidence revealed that younger-onset sporadic colorectal cancer may exhibit unique biological features. To the best of our knowledge, few previous articles reported clinicopathological features in patients with CD-associated anorectal cancer (CDAAC). Therefore, we aimed to clarify the relationship between the younger onset of cancer and clinicopathological characteristics and prognosis, and the efficacy of cancer surveillance in patients with CDAAC.

CD patients who had been diagnosed with intestinal cancers from 1983 to 2020 were collected from 39 Japanese institutions in this study. Of 316 patients with CD-associated intestinal cancers, we analyzed 211 patients with CDAAC. We divided the patients into two groups according to the median age at cancer diagnosis (45 years old).

Younger-onset CDAAC (YO-CDAAC) patients were significantly more likely to have a poor outcome than those with older-onset CDAAC (OO-CDAAC) in terms of both disease-free survival (DFS) (p = 0.0014) and overall survival (OS) (p = 0.023). Multivariate analysis showed that age under 45 years old at diagnosis of cancer was one of the independent factors for poor DFS and OS (hazard ratios: 2.15, 95% confidence interval: 1.09-4.26, p = 0.028, hazard ratios: 1.95, 95% confidence interval: 1.05-3.60, p = 0.033, respectively). Patients detected via surveillance showed significantly better DFS and OS rates than symptomatic patients in YO-CDAAC (p = 0.012 and 0.0031, respectively).

YO-CDAAC may have a poorer prognosis compared with OO-CDAAC. Surveillance could be important to improve cancer prognosis, especially in young CD patients with anorectal disease.

Background & objectives Crohn's disease (CD) is associated with a higher risk of malignancy, which is attributed to disease behaviour and the usage of immunosuppressants. The burden of malignancy in CD is scarcely reported from Asia. We report real-world data on CD-related malignancy from a northern Indian cohort. Methods This retrospective analysis included individuals with CD who were followed up at the All India Institute of Medical Sciences, New Delhi, from 2005 to 2021. The standardized incidence ratio (SIR) was used to calculate the relative risk of malignancy in CD affected individuals compared to the general population. Results In this study, 952 study participants were included, with a mean age at diagnosis of 36.9±15.11 yr; 61.1 per cent were male. The median follow-up duration was 34 months [IQR (interquartile range): 19-73]. Most study participants received steroids (76.7%), immunomodulators (68.7%), or anti-TNF therapy (10.8%). The overall incidence of malignancy was 1.05 per cent, indicating a 10.45 times higher risk in CD [SIR: 10.45; 95% Confidence interval (CI):4.98-17.96]. Eight out of 826, 1 of 106 and 1 of 25 study participants developed malignancy in the first, second and third decades, respectively. The cumulative risk of malignancy was 2.7, 5.5, and 13.4 per cent in the first, second, and third decades, respectively. Regarding bowel malignancies, one study participant each developed ileocaecal adenocarcinoma, anorectal adenocarcinoma, malignant rectal fibrous histiocytoma, and gastric adenocarcinoma. Extraintestinal malignancies included single cases each of follicular neoplasia of the thyroid, neuroendocrine tumour of the pancreatic tail, breast cancer, hepatocellular cancer, oral cancer, and prostate cancer. No cases of lymphoma or skin malignancy were reported. Interpretation & conclusions At 30 yr, the cumulative risk of malignancy among Indian CD-affected individuals was 13.4 per cent, with a SIR of 10.45 (95% CI: 4.98- 17.96). The risk increased with increasing age at disease onset and duration.

Aim: Non-melanoma skin cancers are more common in people with inflammatory bowel disease. However, these tumors can rarely mimic a cutaneous manifestation of the disease, which delays diagnosis and clouds prognosis. Observation: A 35-year-old man with stenosing and fistulizing ileocolic Crohn's disease developed squamous cell carcinoma mimicking a groin fold abscess. After surgical drainage of the abscess, despite antibiotics and therapy combining azathioprine with infliximab, the abscess has recurred. Biopsies revealed a cutaneous squamous cell carcinoma. Palliative radiotherapy-chemotherapy was initiated, but the patient died after 3 months. Conclusion: This observation illustrates the increased risk of non-melanoma skin cancers in inflammatory bowel disease patients, particularly those exposed to thiopurines, and the value of diagnosing them at an early stage.

This study described the clinical characteristics, outcomes, and prognosis of Crohn's disease (CD) patients with anal cancer in a tertiary referral center.

The electronic medical records of 35 adult CD patients, including CD of the pouch, with anal carcinoma evaluated at Mayo Clinic Rochester, Florida, or Arizona between January 1989 and August 2022 were retrospectively reviewed.

Before cancer diagnosis, patients with pouch-related carcinoma had a shorter median duration of inflammatory bowel disease than those with anal carcinoma (10 vs 26 years). Twenty-six patients (74%) had perianal diseases or rectovaginal fistula, and 35% had a history of human papillomavirus infection. Twenty-one patients (60%) were diagnosed with cancer by anal examination under anesthesia (EUA). More than half of adenocarcinomas were mucinous. Sixteen patients (47%) were American Joint Committee on Cancer (AJCC) Tumor Nodes Metastasis (TNM) stage 3, and 83% were treated by surgery. At last follow-up, 57% of patients were alive without cancer. The 1-, 3- and 5-year overall survival rates were 93.8% (95% confidence interval [CI], 85.7%-100%), 71.5% (95% CI, 56.4%-90.7%), and 67.7% (95% CI, 51.2%-87.7%), respectively. Advanced AJCC TNM stage (hazard ratio, 3.20 per stage; 95% CI, 1.05-9.72; P = .040) was significantly associated with increased risk of death, whereas the period of cancer diagnosis in 2011-2022 (HR, relative to 1989-2000, 0.16; 95% CI, 0.04-0.72; P = .017) was significantly related to decreased risk of death.

Anal and pouch-related carcinomas were rare complications of CD, and long-standing perianal diseases were an important risk factor. Anal EUA improved the diagnostic yield. Newer cancer treatment strategies and surgery were associated with excellent survival outcome.

Crohn's disease patients frequently develop perianal fistulas during their life. They are also at higher risk to develop cancers. Rarely, those cancers appear within a prior chronic fistula. The main types are adenocarcinoma mostly mucinous and squamous cell carcinoma. They are generally discovered at an advanced stage with a poor prognosis because symptoms are generally the same as those of the fistula itself. Regular follow-up of chronic fistulas is then important for an early diagnosis as well as histological analysis of the fistula during surgery. There is no consensus on the ideal treatment but abdominoperineal resection is the corner stone with or without neo or adjuvant chemo-radiotherapy. This paper presents a rare case of mucinous adenocarcinoma in a chronic perianal fistula in a Crohn's disease female and provides a review of the literature.

An anal fistula is a fairly common clinical condition, with a very low incidence of malignant transformation. Mucinous adenocarcinoma is a subtype of adenocarcinoma, and its occurrence within perianal fistula tracts is quite rare. This case report describes a 54-year-old male patient with recurrent anal fistula, initially suspected of Crohn's disease (CD), and ultimately diagnosed with perianal mucinous adenocarcinoma. After our joint internal medicine, surgery, and imaging reassessment, the diagnosis was confirmed. Anal fistula is usually considered a benign lesion, but it may also be associated with other diseases. Due to overlapping symptoms of related diseases, the investigation of malignant lesions is often overlooked. This case report emphasizes the importance of timely referral and multidisciplinary management for disease diagnosis and early treatment.

Fistula-associated anal cancer in Crohn's disease (CD) can be challenging to diagnose and treat. Patients with longstanding fistulas in the setting of CD who present with a sudden change in their symptoms should undergo biopsy under anesthesia with extensive sampling, followed by staging imaging. Pelvic magnetic resonance imaging (MRI) can be helpful in identifying the extent of the disease locally. Patients often present in the later stages due to the challenges associated with diagnosing these patients. Two subtypes of this disease include squamous cell carcinoma and adenocarcinoma, and treatment depends on diagnosis. Small sample size and lack of uniform data on treatments make it difficult to say which treatment modalities are optimal, but aggressive combined therapy is likely the best approach for survival. This will include chemotherapy and radiation and often radical resection as well. Despite this, survival is poor, although more recent data suggest that outcomes are improving.

Crohn's Disease (CD) is an Inflammatory Bowel Disease and is characterized by an immune-mediated nature. Its etiology results from the interaction between genetic, enviromental and microbial factors. Regarding pathophysiology, it involves high levels of interleukin (IL)-12, IL-17, and Th1 profile, along with loss of tolerance mechanisms, an increase in pro-inflammatory interleukins, beyond the possibility to affect any part of the gastrointestinal tract. Its symptoms include abdominal pain, chronic diarrhea, weight loss, anorexia, and fatigue, as well as blood in the stool or rectum. Additionally, conditions comprising musculoskeletal, cutaneous, ocular, hepatic, and hematological alterations may be associated with this scenario and extra-intestinal presentation, such as erythema nodosum, anterior uveitis, osteoporosis, and arthritis can also occur. Today, clinical history, exams as fecal calprotectin, ileocolonocopy, and capsule endoscopy can be performed in the diagnosis investigation, along with treatments to induce and maintain remission. In this sense, anti-inflammatory drugs, such as corticosteroids, immunomodulators, and biological agents, as well as surgery and non-pharmacological interventions plays a role in its therapy. The aim of this review is to bring more current evidence to clinical management of CD, as well as to briefly discuss aspects of its pathophysiology, surveillance, and associated disorders.

Crohn's disease (CD) is a chronic inflammatory disease mainly affecting the gastrointestinal tract. With the increased availability of modalities in the last two decades, the treatment of CD has advanced remarkably. Although medical treatment is the mainstay of therapy, most patients require surgery during the course of their illness, especially those who experience complications. Nutritional optimization and ERAS implementation are crucial for patients with CD who require surgical intervention to reduce postoperative complications. The increased surgical risk was found to be associated with the use of corticosteroids, but the association of surgical risk with immunomodulators, biologic therapy, such as anti-TNF mediations, anti-integrin medications, and anti-IL 12/23 was low in certainty. Decisions about preoperative medication must be made on an individual case-dependent basis. Preoperative imaging studies can assist in the planning of appropriate surgical strategies and approaches. However, patients must be informed of any alterations to their treatment. In summary, the management of perioperative medications and surgery-related decision-making should be individualized and patient-centered based on a multidisciplinary approach.

Crohn's disease (CD) is an inflammatory disease that can affect any portion of the gastrointestinal tract (GIT). Although it can present with a number of complications, perianal fistulae are among the most common consequences in patients with CD. In very rare cases, these patients can develop fistula-associated anal adenocarcinoma (FAAA). In this case report, we discuss a 72-year-old man with a long-term history of CD complicated by perianal fistulae, which failed medical and surgical management, ultimately presenting with acute anal pain in the outpatient setting. The physical examination revealed a seton traversing through a fistula surrounded by circumferential granulation tissue suspicious for malignancy. A biopsy of the tissue confirmed grade 3 mucinous-type infiltrating adenocarcinoma of the perianal skin. The patient was diagnosed with an anal verge malignancy associated with a fistula in the context of long-standing CD, and MRI staging demonstrated a T3N1 lesion with potential left inguinal node involvement. He completed neoadjuvant chemo-radiotherapy using capecitabine for five weeks with minimal tumor response, and subsequently, an abdominoperineal resection (APR) was performed with patient discharge on the fifth post-procedure day. Post-operative chemotherapy with oxaliplatin/leucovorin/fluorouracil was administered with minimal complications. Although rare, this report demonstrates the importance of consistent follow-up and mitigation of risk factors in patients with CD, along with the significance of prompt multimodal treatment in the event of developing FAAA.

The aim of this systematic review was to assess the literature on the incidence and risk factors for colorectal cancer and anal cancer in patients with perianal Crohn's disease.

A systematic review of the literature was performed using PubMed, Embase and Google Scholar. A meta-analysis was then conducted using a random-effect model.

Five studies were included in the systematic review. Out of all patients, 26.5% had perianal Crohn's Disease. The median follow-up was six years. In total, 127 cases of colorectal cancer were found (0.43% of the included Crohn's disease patients). Perianal involvement was present in 50% of colorectal cancer patients (0.89% of the population). Three of the studies specified the cancer to be rectal or anal, which were present in 68 and 24 cases (0.3% and 0.1% of patients), respectively. In a subgroup analysis of rectal- and anal cancer, perianal involvement was most frequent in anal cancer, accounting for 46% of the cases. In the rectal cancer group, 37% had perianal involvement. The higher incidence of colorectal cancer in patients with perianal Crohn's was confirmed in a meta-analysis.

Half of patients with colorectal cancer and anal cancer were found to have perianal Crohn's. In patients with perianal involvement, there was a higher percentage of anal cancer compared with rectal cancer. These results support the theory that patients with perianal Crohn's are at increased risk for developing colorectal- and anal cancer. Studies, collecting more detailed data about patients and their cancers, are necessary to further specify the disease course.

As many as 10 million people have died from cancer globally in 2020, making it the top cause of mortality in the globe. Cancer develops as a result of the multi-stage process by which normal cells convert into tumor cells, progressing from a precancerous lesion to a malignant tumor. By avoiding risk factors and applying existing evidence-based preventative techniques, 30%-50% of malignancies may be averted. In order to avoid cancer, it is essential to know the specific causes of the disease. Nidanas, or etiologies, are well-described in Ayurvedic science. Here, the causes of cancer have been outlined so that the knowledge may be used effectively to avoid the disease.

Identification of cancer etiologies that have been described in classics. Evidence-based understanding of these etiologies and to comprehend the significance of etiologies in cancer prevention.

A thorough evaluation of literature, including ancient Ayurvedic classics, modern medical texts, and articles published in reputable journals, was conducted to meet the study's goals and objectives.

According to Ayurveda, there are three distinct phases of tumorigenesis: chronic inflammation, precancerous development, Granthi (a benign glandular swelli ng), and Arbuda (a precancerous tumor) (definite malignancy). A growing body of evidence suggests that the tumor microenvironment, which is predominantly controlled by inflammatory cells, is an essential player in the neoplastic process.

Although inflammation is coming into the picture just now in the contemporary world, Ayurveda has described this as a leading cause 5000 years back. It is evident that diet and lifestyle play a crucial role in the etiology of Shoth (inflammation).