Introduction

There are two approaches for neoadjuvant treatment in locally advanced rectal cancer: conventional radiotherapy (RT) with concomitant chemotherapy and hypofractionated RT. In the RAPIDO study, preoperative hypofractionated RT versus conventional chemo-radiotherapy was proven to be equally effective. In our country and in our center (approximately 90%) previously, the standard treatment was conventional RT, however due to the COVID 19 pandemic in 2020, an increase in the use of hypofractionated RT was observed, this because it was a more accessible therapy for patients due to visits. In our country, the results of hypofractionation therapy compared to a conventional one have not been explored, therefore we decided to compare the outcomes between these modalities.

Aims & Methods

To compare early radiotoxicity of conventional vs. hypofractionated RT.
Methods: Retrospective study conducted in a national reference cancer center at National Institute of Cancer (INCAN) at Mexico City, during the period of April 2020 to December 2020.

Results

We analyzed 61 patients with rectal adenocarcinoma. Locally advanced were 91.8% and metastatic 8.2%. By tumor location upper third 11.4%, middle third 16.4%, middle third 72.1%. Regarding treatment, 72.1% received hypofractionation (25Gy in 5 fractions) and 27.9% conventional (45-50.4 Gy in 25-28 fractions). Techniques used 93.4% 3DCRT, 4.9% IMRT and 1.6% VMAT. Regarding general toxicity, it was observed in 30 patients (68%) in the hypofractionated group and 11 patients (64%) in the conventional treatment group p=0.794. Type of radiotoxicity is described in table 1. We observed a greater radiation mucositis grade 3 in the hypofractionated group compared with standard therapy. The other types were similar with no statistical significance. Table 1.

Conclusion

We observed a considerable increase in the use of hypofractionation in which we did not observe proctitis and cystitis in relation to conventional treatment, however caution and special attention must be exercised in radiation mucositis. We can increase the use of hypofractionated treatment with almost similar radiotoxicities. Further prospective studies are required to confirm these findings.

References

Clinical Case Summary

A 40-year-old male came to our emergency department referring worsening jaundice, mental status deterioration, epigastric pain and anorexia over the past week. Four weeks earlier he presented odynophagia, myalgias, and hand pruritus but didn’t seek medical attention.
Patient’s clinical background included cognitive impairment due to peripartum anoxia and type 2 Diabetes Mellitus. At admission, he had elevated liver enzymes (R value=2,7), coagulopathy (INR 1.3), pancreatic enzymes >3 times the upper normal level and hyperbilirubinemia (mostly conjugated).
The CT-scan revealed pancreatic tail globosity, diffuse abdominal and retroperitoneal peri-centimetric lymph nodes and excluded biliary lithiasis.
After common causes of acute hepatitis and pancreatitis were ruled out, and since patient was at risk of acute liver failure despite supportive treatment, a liver biopsy was performed. Autoimmune hepatitis, drug-induced liver injury or lymphoproliferative disease were held as potential differentials. Hepatitis E Virus (HEV) RNA was then found and genotyped in the serum (genotype 3). HEV infection was assumed as the cause for both hepatitis and pancreatitis. Histological pattern was inconclusive and epidemiological source wasn’t found.

HEV infection paradigm has changed and is now considered an endemic zoonotic infection in most high-income countries (Portuguese seroprevalence is 16.3%)¹. Infection occurs due to ingestion of undercooked pig or boar meat and should be suspected in every acute hepatitis, mostly with a cholestatic pattern.
The setting of acute HEV hepatitis complicated with acute pancreatitis (AP) is uncommon². AP usually starts after a median of 10 days of jaundice onset³. Literature only reports association between AP and HEV caused by genotype 1 from Southeast Asia^{3 4}, and genotype 3 was only related to gallstone-related pancreatitis, according to current knowledge⁵. This might be the first form of HEV genotype 3 infection with hepatitis and pancreatitis.

References

1. Nascimento MSJ, Pereira SS, Teixeira J, et al. A nationwide serosurvey of hepatitis E virus antibodies in the general population of Portugal. Eur J Public Health 2018;28(4):720-24. doi: 10.1093/eurpub/ckx213 [published Online First: 2017/12/14]
2. Debnath P, Datta AK, Chakraborty U, et al. Acute viral hepatitis E complicated with acute pancreatitis in an immunocompetent adult. BMJ Case Rep 2021;14(2) doi: 10.1136/bcr-2020-239684 [published Online First: 2021/02/06]
3. Haffar S, Bazerbachi F, Garg S, et al. Frequency and prognosis of acute pancreatitis associated with acute hepatitis E: A systematic review. Pancreatology 2015;15(4):321-6. doi: 10.1016/j.pan.2015.05.460 [published Online First: 2015/06/08]
4. European Association for the Study of the Liver. Electronic address eee, European Association for the Study of the L. EASL Clinical Practice Guidelines on hepatitis E virus infection. J Hepatol 2018;68(6):1256-71. doi: 10.1016/j.jhep.2018.03.005 [published Online First: 2018/04/04]
5. Karlsson M, Norder H, Bergstrom M, et al. Hepatitis E virus genotype 3 is associated with gallstone-related disease. Scand J Gastroenterol 2019;54(10):1269-73. doi: 10.1080/00365521.2019.1666163 [published Online First: 20190925]

Introduction

Radiation therapy is widely used in the treatment of carcinoma in the abdomen and pelvic cavity, but as a side effect, acute and chronic damage to the gastrointestinal tract may occur. It is well known that the rectum is more prone to radiation damage since it is fixed in the pelvis. Acute symptoms of radiation enteritis are mainly associated with inflammation of the intestinal mucosa and loss of normal mucosa, but changes in gastrointestinal motility due to exposure to high-concentration radiation may also be a cause. Previous studies are demonstrating that patients who received radiation therapy had increased bowel movements, symptoms of urgency, and decreased rectal compliance. But there are only limited studies investigated the pattern of changes in the motility of human rectal smooth muscle following irradiation.

Aims & Methods

This study was conducted to investigate changes in motility and their mechanisms after irradiation in human rectum.
Human rectal tissues were obtained immediately in the operating room from patients undergoing colorectal resection. After removing the mucosal layer of rectum, muscle layer was cut in strips of 5-6 mm in length and 2-3 mm in width. The muscle strips were mounted to an isometric force transducer (Biopac Systems, Inc., Goleta, CA, USA) and suspended in 10 ml organ bath containing aerated (97% O₂ and 3% CO₂) and warmed (36.5 ± 0.5°C) KRB solution. The area under the curve (AUC) for 5 min and tone of spontaneous contractions were analyzed to compared the responses to KCl, ACh (acethylcholine), SNP (sodium nitroprusside), a nitric oxide donor, and ATP (adenosine triphosphate), a purinergic receptor agonist. The mechanical responses were recorded and digitized using Acknowledge software (Biopac Systems, Inc., Goleta, CA, USA). Data were analyzed offline using Clampfit (version 10.2. Molecular devices, San Jose, CA, USA). qPCR was performed for expression of VChAT, NOS1 and PDGFRα to quantify cells mediating cholinergic, nitrergic and purinergic neurotransmission.

Results

KCl and ACh increased the tonic contraction and area under the curve (AUC) in a concentration-dependent manner in both normal and irradiated rectum. The difference in contractile pattern between the two groups was not statistically significant. SNP and ATP decreased AUC and reduced tonic contractions in a concentration-dependent manner in both normal and irradiated rectum. The response to SNP between the two groups was not statistically significant. However, the response to ATP reduced significantly in irradiated rectum compared to normal rectum. In addition, expression of VAChT and NOS1 which are related with cholinergic and nitrergic neurotransmission was not different in both normal and irradiated rectum, however, PDGFRα expression which is related with purinergic neurotransmission was significantly decreased in irradiated rectum compared to normal rectum.

Conclusion

In this study, we analyzed contractile changes in irradiated rectum using neurotransmitters. There were no differences in contractile responses to KCl and ACh and in relaxation response to SNP, however, the relaxation response to ATP was significantly reduced in irradiated rectum. Cholinergic and nitrergic neurotransmission were not changed, however, purinergic neurotransmission was decreased in in irradiated rectum.
These results may explain one of the causes by which increased bowel movements, symptoms of urgency, and decreased rectal compliance in irradiated patients.

Introduction

The implementation of colorectal cancer screening programmes has been associated with an increase in the incidence of malignant polyps removed endoscopically. In those without endoscopic cure criteria, surgery can be performed to improve oncological outcomes.

Aims & Methods

Evaluate factors associated with the presence of residual malignant disease in the surgical specimen after endoscopic removal of a malignant polyp without endoscopic cure.
Retrospective, cohort study including patients with a malignant polyp endoscopically removed without endoscopic cure, who underwent surgery. The absence of endoscopic cure was defined as positive vertical resection margins (< 1 mm), poorly differentiated grade, depth of submucosal invasion > 1 mm, presence of lymphatic or vascular invasion, or presence of tumour budding. Patients with a synchronous neoplastic lesion and those with a malignant polyp without complete endoscopic removal were excluded.

Results

Included 74 consecutive patients submitted to surgery after the endoscopic removal of a malignant polyp without endoscopic cure. Most patients were male (62.2%), with a mean age of 64 ± 10 years. Regarding the endoscopic mucosal resection (EMR), 45 polyps were removed in one fragment (60.8%) and the other 29 were submitted to piecemeal EMR (39.2%). In 15 cases, snare tip spray coagulation (STSC) was performed at the margins of mucosal defects after EMR, 6 in normal-appearing margins (8.1%) and 9 in margins suspected of residual adenomatous tissue (12.2%). Considering the post-operative outcomes, 7 patients required surgical re-intervention (9.5%), 1 was admitted in the intensive care unit (1.4%), 1 patient died (1.4%), and 2 patients required re-hospitalization in the following 6 months (2.7%).
The presence of residual malignant disease in the surgical specimen occurred in 9 patients (12.2%), 7 had intramural disease (9.5%) and 2 had nodal metastasis (2.7%). Patients with polyps with a flat component were 5 times more likely to have residual disease in the surgical specimen (p=0.043). The polyp size and its location in the right colon were not associated with the presence of residual disease in the surgical specimen (p=0.140 and p=0.654, respectively). Patients with polyps submitted to piecemeal EMR were 7 times more likely to have residual disease in the surgical specimen (p=0.024), with 2 patients with residual disease after EMR in one fragment (4.4%) and 7 patients with residual disease from the piecemeal EMR group (24.1%). Those in which STSC was performed were also more likely to have residual disease in the surgical specimen (p<0.001). No statistically significant differences were found between the presence of positive margins, lymphatic or vascular invasion or well or moderately differentiated histologic grade, and the presence of residual disease in the surgical specimen (p=1.000, p=0.675 and p=0.686, respectively). Tumour budding was described in 3 patients, none of which had residual disease in the surgical specimen.

Conclusion

A minority of patients had residual malignant disease in the surgical specimen, with a higher risk for those with polyps with a flat component or that were submitted to piecemeal EMR. In fact, with piecemeal EMR almost one quarter of patients had residual disease e less than 5% of those with EMR in one fragment had residual disease in the surgical specimen, highlighting the need for a careful evaluation of the polyp before endoscopic removal and the importance of removal in one fragment, in case of suspected submucosal invasion.

Introduction

Mast cells are the primary cells that cause acute and chronic colitis due to irradiation causing radiation-induced colitis (RIC). Herein, we investigated whether pre-treatment with tranilast, mast cell inhibitor, could alleviate RIC.

Aims & Methods

A total of 23 Sprague Dawley (SD) rats were randomly divided into three groups control (n=5, C), irradiation group (n=9, RG), and tranilast pre-treated irradiation group (n=9, TG). Tranilast (100 mg/kg) was administered with meal for 10 d to TG, then Gamma ray (20 gray single dose) was irradiated to the pelvis of RG and TG. Ten weeks after irradiation, the rats were euthanized. Rectal tissue samples were stained and the total inflammation score (TIS) and mast cell count were assessed histopathologically. Expression of MUC2, MUC5AC and matrix metalloproteinase (MMP)-9 were also assessed immunohistochemically

Results

Either TIS or some components of TIS including epithelial atypia, vascular sclerosis and colitis cystica profunda, were significantly higher in RG than in TG (p=0.02, 0.038, 0.025, 0.01, respectively). The median number of infiltrating mast cells was significantly higher in the RG (27.5±18.40)) than in TG (6.0±6.02) (P=0.034). Quantitatively, the number of MMP-9-positive cells was significantly higher in the RG (23.67±19.00) than in the TG (10.25±8.45) (p<0.05).

Conclusion

TIS and MMP9 exhibited strong associations (correlation coefficient r=0.6, p<0.05) Immunohistochemically, mucin-lake of CCP showed MUC2 positivity only but was negative for MUC5AC. Conclusively, tranilast pretreatment in RIC shows an anti-inflammatory effect on the RIC with reducing mast cell infiltration and MMP expression

Introduction

Irritable bowel syndrome (IBS) is a bothersome condition with long term pain and bowel symptoms and the most common cause of referral to gastroenterologists in the United Kingdom. Despite this, IBS is poorly understood as a clinical entity. Furthermore, IBS has numerous comorbidities but the full spectrum of these and how they relate to IBS has not been studied.

Aims & Methods

Using clustering analysis on the UK Biobank dataset, an adult cohort (age > 40 years), we aimed to define the top co-morbidities associated with IBS and develop a machine learning model to predict IBS. Co-morbidities in patients based on ICD-10 Summary Diagnosis codes 2 years prior to and 2 years following diagnosis with IBS were assessed and clusters defined. These were compared with a control group of non-IBS patients. Several machine learning algorithms (K-Means, Linear Discriminant Analysis, Gaussian Mixture Models) were compared for accuracy.

Results

Amongst 18000 total adults (aged over 40), 8168 patients coded for IBS, 75% of whom were female. The top ten comorbidities (Table 1) found in IBS patients included diverticular disease, hypertension, hernia, haemorrhoids, osteoarthritis, asthma, gastro-oesophageal reflux disease without oesophagitis, history of psychoactive substance abuse, hypercholesterolaemia, and cholelithiasis. K-Means achieved the highest accuracy (83%) for predicting IBS based on the co-morbidity profile.

Conclusion

Most clusters identified contained obesity, hypercholesterolemia, and hypertension, indicating a possible link with metabolic syndrome. Asthma and allergies suggest a possible cohort of IBS patients with atopy. Further research is needed to establish these links. In clinical practice, this could help both in predicting development of IBS, and also identify the cohorts of IBS on which certain therapies are more likely to work.

References

Drossman, D. A., Camilleri, M., Mayer, E. A., & Whitehead, W. E. (2002). AGA technical review on irritable bowel syndrome. Gastroenterology, 123(6), 2108-2131. doi:10.1053/gast.2002.37095
Snyder, N. (2023, 10 Feb 2023). Irritable bowel syndrome. BMJ Best Practice. Retrieved from https://bestpractice.bmj.com/topics/en-gb/122
Staller, K., Olén, O., Söderling, J., Roelstraete, B., Törnblom, H., Khalili, H., . . . Ludvigsson, J. F. (2021). Diagnostic yield of endoscopy in irritable bowel syndrome: A nationwide prevalence study 1987-2016. Eur J Intern Med, 94, 85-92. doi:10.1016/j.ejim.2021.08.001