Introduction

It is known that there are sex differences in the characteristics of colorectal cancer (CRC), such as incidence and prognosis. However, there is still a lack of understanding on the underlying mechanisms of its sex difference.

Aims & Methods

The aim of this study was to investigate the correlation between the clinicopathological features and the molecular characteristics of CRC depending on sex. 1,068 patients diagnosed with CRC and treated (surgery, chemotherapy or supportive care) at Seoul National University Bundang Hospital were prospectively enrolled. Basic characteristics such as sex, age, and social history, clinical characteristics such as tumor location, stage, and survival were analyzed. In addition, molecular expressions of microsatellite instability (MSI), oncogenes including K-ras, N-ras and H-ras, and DNA mismatch repair genes including MLH-1, MSH-2, MSH-6 and PMS-2 were also investigated.

Results

There were 630 males and 438 females, with a sex ratio of 1.5:1. Risk behaviors for cancer occurrence, such as drinking and smoking, were much more common in males (p < 0.001, respectively). In females, right colon cancer was more frequent than in males (p = 0.022), which seems to be associated with the loss of MLH-1 (p < 0.001) and PMS-2 expression (p = 0.003) (Table). In multivariate regression analyses, older age (p = 0.001), lower BMI (p < 0.001), presence of symptoms (p = 0.048), advanced cancer stage (p < 0.001) and mutation of BRAF (p = 0.030) were significant risk factors for disease-related death. Females showed better overall survival (p = 0.031) as well as disease-specific survival than males (p = 0.088), and this difference was most pronounced in age 40-69 group (overall survival p = 0.024; disease-specific survival p = 0.104, respectively), while not evident in the younger and older age groups (Figure).

Conclusion

Colorectal cancer shows sex differences in various characteristics including incidence, tumor location and prognosis, which might be originated from sex hormone and molecular characteristics.

Introduction

Recently, the increase of young-onset colorectal cancer (yCRC) has been reported, and the age at which colorectal cancer screening is started has been lowered in some countries. Although the characteristics of advanced-stage yCRC or high-grade dysplasias(HGDs) have been reported, there have been few reports of early-stage yCRC or HGDs so far.

Aims & Methods

The aim of this study is to investigate the clinical and pathological characteristics of early-stage yCRC and colorectal HGDs. We retrospectively reviewed the electrical health record data of pathologically diagnosed pT1 colorectal cancers and colorectal HGDs that were resected endoscopically or surgically in our institution from January 2019 to December 2021. The pathological diagnosis was done according to the Japanese Classification of Colorectal Carcinoma. The cases were categorized into two groups: the young group (Y group) or the elderly group (E group). The definition of Group Y and Group E were patients aged 50 years or younger, and those aged 51 years or older respectively. The following factors were evaluated by univariate analysis; age, sex, and the number of experienced endoscopies of the patients; location, size, macroscopic type, histology of the lesion; and depth of invasion. Regarding the morphology or the lesions, 0-Ip, and 0-Is were categorized as protruded lesions, whereas 0-IIa and 0-IIc were categorized as superficial lesions. Statistical analysis was done by the Mann-Whitney U test for continuous variables and Fisher’s exact test for categorical variables. All tests were two-sided, and P<0.05 was considered to be statistically significant.

Results

There were 34 cases in group Y and 314 cases in group E, with a median age (range) of 45 years old (32-50) and 72 years old (51-93), respectively. Sex was male:female=20:14 and male:female=204:110. First-time examination cases were significantly higher in the Y group than in the E group (91.2%:50.6% ;P<0.0001). Regarding the location, the sigmoid colon was the most common in both Y and E groups (55.9%:30.3%). The number of CRC in the left side colon is significantly larger in the Y group than in the E group (79.4%: 62.7%; p=0.0375). In terms of macroscopic type, 0-Ip was most common in group Y(16(41.7%)), whereas 0-lla was most common in group E(137(43.6%)). The number of protruded type early-stage CRC is larger in the Y group than in the E group (82.3%: 58.9%; p=0.005). The median tumor diameter (range) was 16 mm (8-60) and 12 mm (5-155) in Y and E groups respectively. Regarding the histology, well-differentiated tubular adenocarcinoma (Tub1) was the most common histological type in both groups, they were 32(94.1%) in group Y and 282(89.8%) in group E respectively(p=0.4756). pTis (HGDs) were also the most common depth of invasion in both group, they were 25(73.5%) in group Y and 241(77.0%) in group E respectively(p=0.7903).

Conclusion

Compared with early CRC in elderly patients, early-stage yCRC and HGDs were more common in the left side colon and showed a protruded type.

Introduction

Irritable bowel syndrome is one of the most common Disorders of gut-brain interaction, with diarrhea being the predominant subtype. At present, there are limited drugs for effective management of irritable bowel syndrome.
Compound glutamine entersoluble capsules are composed of traditional chinese medicine formulas Sijunzi Tang and L-glutamine. The Sijunzi Tang, which has been used in traditional complementary and alternative integrated medicine, has been used for the treatment of irritable bowel syndrome for many years. However, there is a lack of evidence from modern evidence-based medicine, its clinical efficacy and safety need to be confirmed. L-glutamine has the function of repairing damaged intestinal mucosa.

Aims & Methods

This study performed a multicenter randomized double-blind placebo-controlled withdrawal trial to explore the effectiveness and safety of compound glutamine entersoluble capsules in the treatment of diarrhea predominant irritable bowel syndrome.
The selected participants received the investigational drug for four weeks during the first single arm stage. The responding participants were randomly assigned to the compound glutamine entersoluble capsules and placebo groups in a 1:1 ratio for another 4 weeks.
The primary efficacy endpoint of the study was the response rate of both the improvement in abdominal pain and bowel movements after treatment in randomized controlled trial subjects (50% of the treatment course met the requirement of at least 30% improvement in abdominal pain severity (NRS pain score) and a reduction of at least 50% in bowel movement days for Bristol 6 or 7 types).

Results

A total of 558 subjects in 22 centers, of which 493 subjects were successfully screened and entered the placebo introduction period. During the placebo introduction period, there were a total of 493 subjects, of which 481 subjects were successfully rescreened and entered the single arm period. 437 subjects entered the randomized controlled trial period and were randomly divided into a treatment group of 217 subjects and a placebo group of 220 subjects.
For the primary efficacy endpoint, the number of response cases in the experimental group and placebo group were 114 (54.55%) and 89 (41.20%), respectively (P=0.0059). For secondary efficacy endpoints: (1) The number of improvements in NRS pain scores in the experimental group and placebo group were 138 (66.03%) and 107 (49.54%), respectively (P=0.0006); (2) The number of improved bowel movements in the experimental group and placebo group were 157 (75.12%) and 118 (54.63%), respectively (P<0.0001); (3) The median (quartile) relative baseline change of IBS-SSS scale in the experimental group was -47.00 (-97.00, -14.00) points; The median (quartile) relative baseline change in the placebo group was -17.00 (-63.00, 16.00) points, and there was a statistically significant difference between the two groups (P<0.0001); (4) The median (quartile) relative baseline change of IBS-QOL in the experimental group was -11.46 (-43.01, 0.00) points; The median (quartile) relative baseline change in the placebo group was -3.57 (-39.43,0.00) points (P=0.0007).
During the randomized controlled trial period, the incidence of all adverse events in the 217 subjects in the trial group was 18.89%, the placebo group was 22.27%, the incidence of TEAEs related to the drug in the trial group was 2.30%, and the placebo group was 3.18%.

Conclusion

Compound glutamine entersoluble capsule can effectively improve the clinical symptoms of diarrhea predominant irritable bowel syndrome with a satisfactory safety.

Introduction

Acute infusion-related reactions (IRRs) are common adverse events associated with infliximab, affecting up to 23% of patients. Their etiology involves cytokine release, complement activation, and mast cell degranulation. Consequently, individuals with a history of immunological hypersensitivity reactions are often perceived to be at high risk due to their exaggerated immune responses, and are frequently prescribed premedication.

Aims & Methods

We aimed to determine if patients with immunological hypersensitivity background, receiving infliximab for inflammatory bowel disease (IBD), have an increased risk of IRRs. This retrospective cohort study included all patients diagnosed with IBD who underwent intravenous (IV) infliximab at our centre over a 13-year period. All patients received standard infliximab 2-hour infusion protocol, preceded by premedication with 200mg of IV hydrocortisone. IRRs were defined as any type of mild to severe reaction occurring during infusion or within 2 hours of its completion. Patients were considered to have an allergic predisposition if they had atopic diathesis (such as allergic rhinitis, asthma or atopic dermatitis) or a documented history of allergy to other medications.

Results

Ninety-five patients, with a mean age of 35 ± 13 years at the initiation of infliximab therapy, were included in the study, with females accounting for 52.6%. The majority of patients were diagnosed with Crohn’s disease (n=76, 80%), while the remaining 19 patients (20%) had ulcerative colitis. A history of allergy was reported in 20 patients (21.1%) within the cohort.
Over the study period, a total of 258 person-years (PY) of exposure to infliximab were recorded, with a median of 12 infusions per patient (interquartile range: 5-33). In most cases, infliximab therapy was combined with immunomodulators (n=63, 66.3%).
Fourteen IRRs occurred during the follow-up period, resulting in an overall incidence rate of 49.5 per 1000 PY. Patients with and without a history of immunological hypersensitivity showed comparable incidence rates of IRRs (32.5 per 1000 PY and 57.8 per 1000 PY, respectively), as well as similar cumulative incidence (15% and 22.7%, respectively). No statistically significant difference was observed between the two groups (p=0.446).

Conclusion

Having an immunological hypersensitivity background does not appear to increase the risk of developing acute infliximab infusion-related reactions. Consequently, it does not warrant specific premedication or additional precautionary measures.

Clinical Case Summary

Crohn’s disease (CD) is a multi-factorial immune-mediated inflammatory condition of the gastrointestinal tract (GIT). While CD-related granulomas typically occur within the GIT, they can appear in other areas such as lymph nodes, mesentery, peritoneum, liver, and lungs. This case highlights a rare instance of renal granuloma secondary to CD and discusses an effective treatment approach. An 18-year-old male presented to a GP with a one-year history of abdominal pain. There was no significant medical or family history. Physical examination was unremarkable. Laboratory findings showed raised white cell count, elevated erythrocyte sediment rate, and renal dysfunction. He was referred to a nephrologist who noted additional symptoms of diarrhoea and occasional per-rectal bleeding with no significant improvement in symptoms or renal function after complete cessation of non-steroidal anti-inflammatory drugs. Renal biopsy confirmed acute interstitial nephritis and granuloma, therefore he was referred to a gastroenterologist to rule out CD or sarcoid. Colonoscopy showed pancolitis with rectal sparing and segmental biopsies revealed chronic colitis with granulomas confirming CD. Fecal calprotectin was raised. Further investigations ruled out autoimmune disease, tuberculosis and sarcoidosis as causes for renal impairment. Treatment involved steroid tapering followed by intravenous infliximab induction and maintenance therapy with subcutaneous injections fortnightly. Renal function and GIT symptoms improved with infliximab monotherapy, though dose escalation to weekly infliximab injections was required at seven months due to loss of response from subcutaneous infliximab. At one year, colonoscopy showed endoscopic remission, with ongoing improvement in renal function (creatinine 194 to 111 umol/L) and resolution of pyuria. In conclusion, we present a rare case of CD-associated interstitial nephritis, showing a positive clinical response to infliximab monotherapy.

References

1. Lamb CA, Kennedy NA, Raine T, et al. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut. 2019;68:s1-s106.
2. Eade MN, Cooke WT, Williams JA. Liver disease in Crohn's disease. Scand J Gastroenterol. 1971;6:199-204.
3. Whitehead R. Pathology of Crohn's disease. In: Kirsner JB, Shorter RG, eds. Inflammatory bowel disease. 2nd ed. Philadelphia: Lean and Febiger; 1980:296-310.

Disclosure

Nil

Introduction

Ulcerative colitis (UC) is a chronic intestinal inflammatory disease mainly involving the mucosa and submucosa. The pathogenesis of UC has not been clearly elucidated and there are limitations of existing treatment measures. Dietary factors have been implicated closely related to the pathogenesis and clinical outcome of UC. Our team in the early clinical trials observed that UC patients had aggravation or recurrence of their disease after taking in lamb. However, the relationship between them is unclear. Does lamb aggravate the intestinal inflammation of UC patients? What is the mechanism if lamb has a negative impact on intestinal inflammation? It is urgent for us to study further.

Aims & Methods

We aimed to clarify the effect of lamb on intestinal inflammation in UC mice and to reveal the mechanism, so as to provide scientific basis for clinical dietary guidance for UC patients.
Mice were given 2.5% DSS (w/v) solution for 5 days and deionized water for 7 days for 1 cycle, repeated 3 cycles to establish the chronic UC model. Take the start of giving DSS solution as day1, corresponding measures of lamb suspensions at a dose of 0.25, 0.50, 1.00 g/mL or sterile water were administered for 31 days. Then the general condition and the severity of colitis were monitored. Colon tissues were obtained to assess the degree of pathological damage by HE staining and detect the levels of key factors of intestinal barrier by RT-qPCR. Spleen tissues were collected to detect the levels of M1/M2 macrophages and related factors by flow cytometry and RT-qPCR.

Results

Our results showed that lamb aggravated intestinal inflammation of UC mice, as indicated by higher weight loss and DAI, shorter colon and more severe pathological damage. Also, the colonic mechanical barrier-associated factors including ZO-1, Claudin-1, Occludin, E-cadherin mRNA and colonic mucosal barrier associated-factors such as Muc1, Muc2, Muc3 mRNA showed significant decrease in lamb-treated colitis mice. Moreover, colitis mice with lamb treatment showed significant increased M1 macrophages and reduced M2 macrophages in the spleen, leading to an increased the ratio of M1/M2 macrophage. Meanwhile, the M1 macrophage-associated inflammatory factors gene TNF-α, IL-6 mRNA increased and M2 macrophage-associated inflammatory factors gene IL-10, TGF-β mRNA decreased significantly in lamb-treated colitis mice.

Conclusion

Our results show that lamb aggravates the intestinal inflammation and damages the mucosal barrier of colitis mice, whose mechanism is related to the promotion of macrophages to M1 cells and inhibition M2 cells differentiation, thereby aggravating the imbalance of M1/M2 macrophages.