Introduction

Inflammatory bowel disease (IBD) and endometriosis are both immuno-mediated chronic inflammatory diseases, sharing some common clinical manifestations (i.e. abdominal pain). A possible association between IBD and endometriosis has been suggested but is currently still undefined.

Aims & Methods

In a multidisciplinary prospective single-center study, we aimed to assess the frequency of undiagnosed endometriosis in IBD patients by searching for symptoms compatible with this condition (dysmenorrhea, dyschezia, dyspareunia, dysuria, heavy menstrual bleeding, HMB). Secondary end point was to compare symptoms compatible with endometriosis in IBD patients with vs without a subsequent diagnosis of endometriosis. In a prospective study, all female IBD patients in childbearing age with symptoms compatible with endometriosis, as revealed by filling a questionnaire during a scheduled visit at our IBD center, were enrolled. After informed consent, gynecological evaluation and transvaginal ultrasonography (TVUS) was performed by our referral dedicated gynecologist, in order to search for pelvic endometriosis. Inclusion criteria: 1) female gender; 2) age ≥18 and ≤50 years; 3) well-defined diagnosis of IBD; 4) ≥1 symptom compatible with endometriosis; 5) written informed consent. Exclusion criteria: 1) pregnancy; 2) menopause. Characteristics of endometriosis and adenomyosis were reported according to standard classifications. Data were expressed as median [range].

Results

The study population included 51 IBD patients (age 37 [23-53] years, body mass index 21.6 [17.3-41.6]). In IBD, there were 24 (47.05%) Crohn’s Disease (CD) and 27 (52.9%) Ulcerative Colitis (UC) patients. At enrollment, questionnaires revealed dysmenorrhea in 43 (84.3%), dyschezia in 18 (35.3%), dyspareunia in 31 (60.8%), dysuria in 4 (7.8%), HMB in 33 (64.7%) patients. At TVUS, endometriosis in any form was observed in 35 (68.6%) IBD patients, adenomyosis in 26 (51%). Both diseases were concomitantly detected in 22 patients (43.1%). In patients showing endometriosis, deep infiltrating endometriosis was diagnosed in 33 (94.3%) IBD patients, and 7 out of these 33 (21.2%) patients showed rectal endometriosis. Among the 35 patients with endometriosis, IBD included CD in 16 (45.7%) and UC in 19 (54.3%). The frequency of the tested 5 symptoms compatible with endometriosis were then compared between IBD patients with vs without a subsequent diagnosis of endometriosis. Dysmenorrhea (32 [91.4%] vs 11 [68.75.4%]; p=0.04) and HMB (26 [74.3.%] vs 7 [43.75%]; p=0.04) were more frequent in IBD patients with endometriosis. Differently, the other considered symptoms were comparable between IBD patients with vs without endometriosis: dyspareunia (24 [68.6%] vs 7 [43.75.%]; p=0.09), dyschezia (11 [31.4%] vs 7 [43.7%]; p=0.39), dysuria (3 [8.6%] vs 1 [6.25%]; p=0.77). No significant differences were observed between UC and CD patients in terms of characteristics of endometriosis, when excluding a higher frequency of endometriosis involving the uterosacral ligament in UC vs CD (16 [84,2%] vs 6 [36.5%]; p=0.005).

Conclusion

Findings from a prospective multidisciplinary study suggest that endometriosis may be highly underestimated in IBD and that specific symptoms, particularly dysmenorrhea and HMB, should be carefully searched in young patients. In IBD, endometriosis was mostly represented by deep infiltrating endometriosis and a higher frequency of rectal endometriosis, potentially leading to rectal bleeding was observed.

References

[1] J. Satsangi, MS Silverberg, S. Vermeire, and J‐F. Colombel. The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications. Gut 2006; 55(6): 749–753.
[2] American Society for Reproductive Medicine. Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril 1997;67:817–821.

Introduction

Inflammatory bowel disease (IBD) and endometriosis are immuno-mediated chronic inflammatory conditions, with possible shared clinical manifestations (i.e. abdominal pain). The association between IBD and endometriosis is undefined.

Aims & Methods

In a multidisciplinary prospective study, the primary end point was to search and characterize endometriosis in IBD patients (pts) assessed for compatible symptoms. Secondary end point was to identify risk factors for endometriosis among symptoms more frequently associated with this condition in IBD. Characteristics of endometriosis were also compared between Crohn’s Disease (CD) and Ulcerative Colitis (UC).
In a prospective study, all female IBD pts fulfilled a questionnaire to sear for symptoms compatible with endometriosis (dysmenorrhea, dyschezia, dyspareunia, dysuria, heavy menstrual bleeding, HMB). Gynecological evaluation and transvaginal ultrasonography (TVUS) were performed by referral dedicated gynecologist in eligible pts. Inclusion criteria: 1) female gender; 2) age ≥18 and ≤55 years (yrs); 3) well-defined diagnosis of IBD; 4) ≥1 symptom compatible with endometriosis; 5) written informed consent. Exclusion criteria:1) pregnancy; 2) menopause. Characteristics of endometriosis and adenomyosis were reported according to standard classifications. Data were expressed as median [range], difference assessed by chi-square test, Student-t-test and Mann-Whitney U-test, risk factors for endometriosis were searched by uni- and multivariate logistic regression analysis.

Results

The study population included 82 IBD pts with symptoms compatible with endometriosis (dysmenorrhea in 71 [86.5%], dyschezia in 27 [32.92%], dyspareunia in 49 [59.75%], dysuria in 4 [4.87%], HMB in 48 [58.53%]). In IBD group (age 38 [17-53] yrs, BMI 21.8 [17.3-41.6]) there were 41 (50%) pts with CD, 41 (50%) with UC. Among the 82 IBD pts, TVUS detected endometriosis in 51 (62.1%). Among the 51 IBD pts with endometriosis detected by TVUS, there were 21 (41.17%) CD and 30 (58.8%) UC. Deep infiltrating endometriosis (DIE) was diagnosed in 46 (90.19%) IBD pts. Dysmenorrhea, dyspareunia and HMB were more frequent in IBD pts with vs without endometriosis (48 [94.11%] vs 23 [74.1%]; p=0.025; 36 [70.58%] vs 13 [41.93%]; p=0.019, 35 [68.62%] vs 13 [41.93%]; p=0.03 respectively). Differently, the other tested symptoms were comparable between IBD pts with vs without endometriosis: dyschezia (17 [33.33%] vs 10 [32.5%]; p=0.88), dysuria (3 [5.88%] vs 1 [3.22%]; p=0.9). When comparing characteristics of endometriosis in IBD, a higher frequency of endometriosis involving the uterosacral ligament was detected in UC vs CD (27 [90%] vs 8 [38.09%]; p=0.0002). After univariate and multivariate analysis, dysmenorrhea and HMB were indentified as significant risk factors for endometriosis (4.42 [1.01-20.41], p=0.04 and 3.66 [1.33-10.1], p=0.01, respectively).

Conclusion

Endometriosis may be highly underestimated in IBD, being mostly represented by DIE, requiring an expert evaluation for the diagnosis. Dysmenorrhea and HMB, identified as significant risk factors for endometriosis, should be carefully searched in young fertile IBD patients for a timely diagnosis and treatment.

Introduction

Inflammatory bowel disease (IBD) and endometriosis are immuno-mediated chronic inflammatory diseases observed in young women, sharing some of the clinical manifestations (i.e. abdominal pain). The possible association and the relationship between endometriosis and IBD is undefined.

Aims & Methods

In a multidisciplinary approach, we aimed to assess in patients with IBD and concomitant endometriosis, the clinical outcome in terms of abdominal pain and endometriosis-related symptoms at 6 and 12 months and characteristics of endometriosis. All female IBD pts in childbearing age referring symptoms compatible with endometriosis were enrolled and referred to dedicated gynecologists for transvaginal ultrasonography (TVS). Inclusion criteria: 1) female gender; 2) age ≥18 and ≤55 years; 3)well-defined diagnosis of IBD; 4) symptoms compatible with endometriosis; 6) consent. Exclusion criteria: 1) pregnancy; 2) menopause; 3) suspected pelvic malignancy at TVS. Characteristics of IBD, endometriosis and adenomyosis were classified according to standard criteria. Data were expressed as median [range]. The Student-t Test and χ2 test were used for comparisons.

Results

Endometriosis was diagnosed in 25 (71%) out of 35 IBD patients with compatible symptoms. These 25 IBD pts included 12 (48%) Crohn’s Disease (CD) and 13 (52%) Ulcerative Colitis (UC). CD and UC patients were comparable in terms of age (38 [28-47] vs 39 [25-53]; p=0.75). IBD characteristics included: IBD duration: 11.5 [1-35], CD 11 [1-25] vs UC 12 [1-35] years; p=0.8, CD localization: ileum 4 (33.3%), colon 1 (8.4%), ileum-colon 7 (58.3%), CD behavior: non-stricturing non-penetrating 6 (50%), stricturing in 3 (25%), penetrating in 3 (25%) pts, UC extent: proctitis 3 (23%), left-sided 5 (38.5%), pancolitis in 5 (38.5%) pts. Other IBD characteristics did not differ between CD and UC pts with endometriosis. In IBD patients with endometriosis, a comparable frequency of dysmenorrhea (9 [75%] vs 13 [100%] pts; p=0.47), dyschezia (5 [41.7%] vs 6 [46.1%] pts; p=0.85), dyspareunia (9 [75%] vs 10 [76.9%] pts; p=0.72), dysuria (0 [0%] vs 3 [23.1%] pts; p=0.24) was observed between CD and UC. At transvaginal ultrasonography, deep infiltrating endometriosis was observed in all thr 25 patients with IBD and endometriosis. Moreover, a high frequency of rectal endometriosis was detected in these 25 IBD pts (6 [24%]). Adenomyosis was observed in 19 (76%) IBD pts with endometriosis, with no differences between CD and UC (8 [66.6%] vs 11 [84.6%]; p=0.56).
Among the 25 IBD pts with endometriosis, 10 (40%) underwent dienogest or estroprogestinic treatment. At 6 months, gynecological follow up was available in 9 pts, of whom 7 were on dienogest or estroprogestinic treatment. Among these 7 pts, 4 reported no endometriosis-related symptoms and 5 no abdominal pain. At 12 months, gynecological clinical follow-up currently includes 6 pts (25%), all on progestinic treatment. Of these, only 2 pts reported abdominal pain while 3 pts reported recurrence of endometriosis-related symptoms.

Conclusion

In the tested population, endometriosis was present in half of IBD pts with compatible symptoms, particularly DIE, with a high rate of rectal endometriosis. After endometriosis treatment, a lower proportion of patients referred abdominal pain. Endometriosis, often mimicking IBD, should be searched and treated in IBD young patients in order to avoid ineffective treatments.

Introduction

In Inflammatory Bowel Disease (IBD), histological assessment of colonic biopsies may detect areas “indefinite for dysplasia” (IND). This definition is used when a definite distinction between non-neoplastic changes and neoplasia is not possible(1). The role of this finding in predicting the endoscopic and histological findings in IBD colitis is currently undefined.

Aims & Methods

Primary aim was to evaluate the outcome of IBD patients(pts) with an initial histological finding of areas IND in random colonic biopsies, followed up for ≥ 3 years. At this purpose, all IBD pts showing areas IND in colonic biopsies taken from March 2018 to March 2022, subsequently followed up for ≥3 years including ≥ 1 control colonoscopy were retrospectively enrolled. All pts were in regular follow up at our referral IBD Unit and underwent colonoscopy with histological assessment in the same center.

Results

The study population included 99 pts with IBD colitis and histological aspects IND detected in random colonic biopsies in 79(79.8%) pts and in target biopsies in 20(20.2%) pts. In the 79 pts, areas IND were detected in random biopsies taken from: rectum in 62(78%), left colon in 29(36%), transverse colon in 6(7.5%), right colon in 5(6.3%), >1 area in 18(22.3%) pts. In the 20 pts with areas IND on target biopsies, these were taken from stenosis (5 pts), polyps (9 pts), lateral spreading tumors (2 pts), flat elevated mucosa (4 pts). For the aim of the study, only the 79 IBD pts (37 females, 46.8%) showing in random colonic biopsies areas IND were considered. These 79 IBD pts (69 UC, 9 CD, 1 unclassified colitis) showed median age of 51 [18-79], long-standing IBD in 54(68.4%), family history of CRC in 11(13.9%), concomitant primary sclerosing cholangitis in 1(1.3%) pt. Random biopsies were taken from colonic mucosa proximal to ulcerations in 54(68.4%) pts, erosions in 19(24%) pts and to mild inflammation in 6(7.6%) pts. The second colonoscopy was performed after a median of 11[1-42] months. In the 79 pts with a first evidence of areas IND on random biopsies, the second colonoscopy detected: dysplasia in 10(12.6%) pts (high grade, HGD in 2[2.5%], low grade dysplasia, LGD in 8[10.1%]pts), areas IND in 12(15.2%) pts, no dysplasia (HGD, LGD or IND) in 38(48.1%) pts, while in the remaining 16(20.3%) pts no reliable histology was available. LGD at second colonoscopy was detected in random biopsies (4pts) or in target biopsies (4pts). Differently, in both pts with HGD it was detected in target biopsies, including one focal area of adenocarcinoma (CRC) in 1(1.3%) pt. Areas IND confirmed at second colonoscopy were detected in the same colonic segment in 11(13.9%) pts and in a different segment in 1(1.3%) pt. After the second colonoscopy, 4 out of the 79 IBD pts required IBD-related colonic surgery, and histology of the surgical specimen detected LGD in 1 pt, CRC in 1 pt and areas IND in 2 pts. During the study period (median 27[2-75] months) 51 out of the 79(64.5%) IBD pts repeated a third colonoscopy detecting: areas IND in 4(7.8%), LGD in 6(11.8%), HGD in 1(2%) pts and no CRC.

Conclusion

Patients with IBD colitis showing areas indefinite for dysplasia deserve careful endoscopic surveillance as dysplasia and CRC may be detected at subsequent colonoscopies.

References

1. Feakins R, Borralho Nunes P, Driessen A, Gordon IO, Zidar N, Baldin P, Christensen B, Danese S, Herlihy N, Iacucci M, Loughrey MB, Magro F, Mookhoek A, Svrcek M, Rosini F. Definitions of Histological Abnormalities in Inflammatory Bowel Disease: an ECCO Position Paper. J Crohns Colitis. 2024 Feb 26;18(2):175-191.

Introduction

Whether using immunomodulators (IMM) or biologics after a first cancer in Inflammatory Bowel Disease patients (pts) may increase the risk of new or recurrent cancer is undefined.

Aims & Methods

The primary aim was to assess the frequency of new or recurrent cancer in IBD pts treated with IMM or biologics after a previous diagnosis of cancer. The secondary aim was to evaluate the cancer-related mortality in IBD pts treated with IMM and biologics after the first cancer. In a retrospective, multicentre study, clinical records of all IBD pts treated with IMM or biologics after a previous diagnosis of cancer were reviewed. Inclusion criteria:1) Diagnosis of Crohn’s Disease (CD) or Ulcerative Colitis (UC); 2)Cancer history;3)IMM or biologics used after a first cancer;4)IBD and cancer data recorded; 5)Follow-up after cancer ≥4 months (mos). Exclusion criteria:1) IMM used for ≤3 mos. Data considered: IBD features,cancer type,IBD duration, age at diagnosis of cancer, follow-up after cancer,cancer-related death.Data expressed as median [range].

Results

75 IBD pts (57 CD,18 UC) treated with IMM or biologics after a first diagnosis of cancer were enrolled (n [%]: F 36 [48%];age 61 [26-89] yrs).CD features included (n=):L1 (37);L2 (2);L3 (16);L4 (8);B1 (17);B2 (30);B3 (10).UC extent included: E1 (2),E2 (8), E3 (8). Cancer in IBD pts treated with IMM/biologics included (n [%]):basal cell carcinoma (BCC) 14 (18.4%), breast 9 (12%),colorectal 9 (12%),melanoma 8 (10.7%),prostatic or testicular 7 (9.3%), urinary tract 7 (9.3%),thyroid 6 (8%),squamous cell carcinoma (SCC) 4 (5.3%),endometrial 2 (2.7%),hematopoietic 4 (5.3%),others 7 (9.3%).In 2 (2.7%) pts, ≥2 cancers occurred. The median time interval between index cancer and ISS/biologics use was 38 mos [0-428]. IMM after cancer were used for a median of 32.5 [4-131] mos, including: methotrexate (MTX) in 13 (17.3%),thiopurines in 8 (10.7%),mycophenolate mofetil,tacrolimus or everolimus in 3 (4%) pts.Biologics were used after cancer for a median of 36 [3-194] mos:Ustekinumab (UST) in 24 (32%),Vedolizumab (VDZ) in 31 (41.3%),Adalimumab (ADA) in 17 (22.7%), Infliximab (IFX) in 12 (16%),Tofacitinib (Tofa) in 2 (2.7%),Golimumab in 1 (1.3%) pt. Both IMM and biologics were used after a first cancer in 15 (20%),while ≥2 biologics in 16 (%) pts.In a median follow up of 95 [4-509] mos after the first cancer, 8 (10.7%) IBD pts developed a new and/or recurrent cancer after IMM/biologics use.In particular, cancer recurred in 3 (4%) pts (1 melanoma,1 prostatic,1 colonic adenocarcinoma), while new cases of cancer occurred in 6 (8%) pts,all 6 represented by non-melanoma skin cancer (NMSC) (both recurrent and new cancer in 1 pt).A not significant trend for a higher frequency of new vs recurrent cancer (p=0.47) was observed.No cancer-related death were observed.

New and recurrent cancers after IMM/biologics

Conclusion

In a retrospective multicentre study, a low frequency of recurrent cancer was observed in IBD pts using IMM or biologics after the first cancer. A not significant trend for a higher frequency of new vs recurrent cancer (p=0.47) was observed, being almost all new cancers represented by NMSC.

Introduction

Whether using Immunomodulators (IMM) as immunosuppressors (ISS), biologics or JAK inhibitors (JAKi) after a diagnosis of cancer in Inflammatory Bowel Disease (IBD) patients (pts) may increase the risk of new or recurrent cancer is undefined.

Aims & Methods

Primary aim: to assess the frequency of new/recurrent cancer in IBD pts treated with IMM after a diagnosis of cancer. Secondary aims: to evaluate in the same population the cancer-related mortality and risk factors for recurrence or new malignancy. In a retrospective multicentre Italian study, clinical records of all IBD pts treated with IMM after a diagnosis of cancer were reviewed. Inclusion criteria: 1) Diagnosis of Crohn’s Disease(CD) or Ulcerative Colitis(UC); 2)History of cancer; 3)Clinical outcome after cancer ≥6 months (mos). Exclusion criteria: 1)IMM used for ≤3 mos or ≤3 administrations; 2)missing data. Data expressed as median[range], differences assessed with Student t-test and X-square test, univariate analysis performed to search for risk factors for new or recurrent malignancy.

Results

Study population included 122 IBD pts (84 CD, 38 UC) treated with IMM after cancer (Female 58 [47.5%]; age: 59.5[26-89] yrs). Index cancer was: genitourinary in 18(14.8%), non-melanoma skin cancer (NMSC) in 17(13.9%), breast in 15(12.3%), melanoma in 14(11.4%), thyroid in 13(10.6%), colon (CRC) in 11(9.0%), hematopoietic in 9(7.4%), prostate in 8(6.6%), neuro-endocrine in 4 (3.3%), head-neck, liver and endometrial in in 3(2.5%), other in 3(2.5%), lung in 1(0.8%). ISS used after cancer (duration: 29[4-200] mos) included: thiopurines in 10(37%), methotrexate in 14(51.9%), others in 3(11.1%) pts. Biologics or JAKi used after cancer (duration: 24[3-180] mos) included: Anti-TNF in 36(32.4%), VDZ in 60(53.6%), UST in 45(40.2%), JAKi in 9 (7.3%) and others in 6(5.4%) pts.The median time interval between cancer and IMM use was 27[0-312] and 48[1-432] mos, respectively. In a median follow up of 8[1-45] yrs after index cancer, 12 (9.8%) IBD patients developed new or recurrent malignancy after IMM use. There were 4 recurrent neoplasms (2 prostatic, 2 thyroid) and 7 new malignancy (7 NMSC,1 salivary gland carcinoma, 2 melanoma and 1 CRC). No cancer-related death occurred. No differences were observed in terms of IBD phenotype and IMM treatments between patients with vs without new/recurrent malignancy. At univariate analysis, when considering age at malignancy, smoking habits, gender, IMM treatment and duration before and after index cancer and treatment for malignancy, no predictive factors for new/recurrent malignancy were observed.

Conclusion

A low frequency of new or recurrent cancer was observed using IMM after cancer in IBD. No risk factors for new/recurrent malignancy were observed.

References

1. Gordon H. et al. ECCO Guidelines on IBD and Malignancies, Journal of Crohn's and Colitis, 2023

Introduction

Colorectal cancer (CRC) risk is increased in patients with long-standing colitis related to Inflammatory Bowel Disease (IBD). A higher frequency of mucinous and signet-ring colonic adenocarcinoma has been suggested in IBD, but risk factors for these histotypes of CRC are undefined.

Aims & Methods

Primary aim was to compare the frequency of mucinous and signet-ring adenocarcinoma in patients with vs without IBD. Secondary aims were to search for IBD-related risk factors for signet ring and mucinous adenocarcinoma and to compare the localization of these histotypes of CRC in patients with vs without IBD. From January 2002 to January 2023, all IBD patients with concomitant colorectal adenocarcinoma (Cases) were retrospectively enrolled. Each Case was matched with 2 patients with CRC and no IBD (Controls) for age at CRC diagnosis (±5 years). Inclusion criteria for Cases and Controls: 1) age ≥18; 2) well-defined diagnosis of CRC. Additional inclusion criteria for Cases: well-defined diagnosis of IBD, classified according to standard criteria. Exclusion criteria: Missing histological and surgical report. Data were expressed as median [range]. Student-t Test and χ2 test were used for comparisons. Univariate logistic regression model was applied for assessing risk factors for mucinous and signet-ring CRC (OR [95%CI]).

Results

The study population included 120 patients with colorectal adenocarcinoma: 40 IBD patients and 80 non-IBD Controls. CRC in the 40 IBD patients occurred in 24 (60%) patients with Ulcerative Colitis (UC) and in 16 (40%) with Crohn’s Disease (CD). In patients with CRC, no differences were observed between IBD and non-IBD Controls in terms of gender (F) (13 [32.5%] vs 35 [43.7%]; p=0.32) and median age at diagnosis of CRC (54 [29-80] vs 58 [31-83] years; p=0.19). CRC in IBD was histologically defined as mucinous/ signet-ring in 17 (42.5%) and standard adenocarcinoma in 23 (57.5%) patients. Mucinous/signet ring CRC more frequently occurred in patients with IBD vs non-IBD Controls (17 [42.5%] vs 18 [22.5%], p=0.03). In IBD patients, rectal localization of CRC was significantly more frequent in mucinous/signet-ring vs standard CRC (4 [17.4%] vs 8 [47.1%]; p=0.04). In stricturing CD, there was a significantly higher frequency of standard vs mucinous/signet-ring CRC (7 [77.8%] vs 1 [14.4%]; p=0.04). Other IBD characteristics did not differ in relation to the 2 CRC histotypes, including gender (F): 8 [34.8%] vs 5 [29.4%]; p=0.98 and IBD duration at CRC diagnosis (14 [1-45] vs 17 [1-36]; p=0.74). In IBD, CRC stage at diagnosis was comparable between patients with standard vs mucinous/signet-ring CRC (stage I: 6 [26.1%] vs 1 [5.9%]; p=0.21; II: 9 [39.1%] vs 4 [23.5%]; p=0.48; III: 5 [21.7%] vs 7 [41.2%]; p=0.71; IV: 3 [13.1%] vs 5 [29.4%]; p=0.37)). At univariate analysis, no IBD-related risk factors for mucinous/signet-ring CRC were detected.

Conclusion

In the tested cohort, mucinous and signet-ring adenocarcinoma was more frequently observed in IBD than in non-IBD controls, although no IBD-related risk factors were identified. A higher frequency of rectal involvement is suggested for mucinous/signet-ring vs standard adenocarcinoma in IBD.