Introduction

There are around 12,400 new cases of head and neck cancer diagnosed in the UK each year. It is the 8^th most common cancer in the UK and incidence rates are projected to rise by 3% over the next two decades. Between 33 and 69% of patients with Head and Neck cancer will require enteral feeding via a gastrostomy tube to support their nutrition and hydration during treatment. Percutaneous endoscopic gastrostomy (PEG) is often the preferred method of placement of the gastrostomy tube and is generally considered safe but malignant seeding of the tumour to the PEG site is a rare complication. It has been reported that rate of metastasis at the PEG site is between 0.5-3%.

Aims & Methods

We carried out a retrospective chart review of all patients undergoing PEG insertion at the Bristol Royal Infirmary between January 2015 and December 2021. The primary aim was to determine the rate of PEG site metastases at our centre. Demographic data were collected, as well as cancer type and stage, details of disease progression.

Results

A total of 284 patients underwent PEG insertion during the period of data collection. Of these, 204 patients had their gastrostomy inserted for a head and neck cancer indication. All PEG tubes were put in using the ‘pull’ method. 2 patients were identified as having abdominal metastatic disease and these cases were reviewed in greater detail. On further review these 2 patients were not found to have malignant spread to the PEG site specifically, but more general peritoneal disease, unrelated to the method of gastrostomy insertion. For both patients, the abdominal disease was in the context of widespread metastatic disease. There were therefore no cases of PEG site metastases at our centre between January 2015 and December 2021 (0/204, 0%).

Conclusion

Our data suggests that PEG is a safe method of gastrostomy insertion for head and neck cancer patients, without significant risk of tumour seeding to the PEG site.

References

https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/head-and-neck-cancers#heading-Five
Greaves JR. Head and Neck Cancer Tumor Seeding at the Percutaneous Endoscopic Gastrostomy Site. Nutr Clin Pract. 2018 Feb;33(1):73-80.
Huang AT, Georgolios A, Espino S, et al. Percutaneous endoscopic gastrostomy site metastasis from head and neck squamous cell carcinoma: case series and literature review. J Otolaryngol Head Neck Surg. 2013 Feb 28;42(1):20.
Vamsi, Arthi; Ragunathan, Karthik; Puli, Srinivas. Malignant Seeding Following Percutaneous Endoscopic Gastrostomy Placement in Head and Neck Cancer: Review of Literature: 1900. American Journal of Gastroenterology 109():p S563, October 2014.

Disclosure

No conflicts of interest to declare.

Introduction

Gastrointestinal bleeding is a frequent reason for emergency room visits and one of the main digestive emergencies. Direct oral anticoagulants (DOACs), vitamin K antagonists (VKAs) and anti-platelet agents (APAs) frequently prescribed in cardiac patients increase the risk of Gastrointestinal bleeding . The aim of our work is to study the characteristics of Gastrointestinal bleeding in the cardiac patient.

Aims & Methods

This is a prospective comparative and analytical study between April 2020 and August 2022. We included cardiac patients who presented with Gastrointestinal bleeding and benefited from endoscopic exploration within our training, which we compared with a control group of patients explored for Gastrointestinal bleeding without cardiac comorbidity. We took into account age, sex, history, average length of hospital stay, need for transfusion and ICU stay, and outcome after the bleeding episode. SPSS 20.0 software was used for statistical analysis.

Results

378 patients underwent endoscopic exploration for Gastrointestinal bleeding during this period, including ( oesophago-gastro-duodenoscopy (EGD), colonoscopy and endoscopic videocapsule).
We collected 47 patients with underlying cardiac pathology and 331 non-cardiac patients. The mean age was 70.76 years [34-90]. The sex ratio was M/F=1.13.
18 patients (38.3%) had ischemic heart disease, 11 (23.4%) had arrhythmic heart disease, 8 (17%) had valvular heart disease, and 10 (21.27%) had heart disease of other etiologies.
14 patients (29.78%) were on anticoagulants alone, including 13 (92.86%) on VKA and 1 (7.14%) on DOAC, 13 (27.66%) were on anti-platelet agents alone, 12 (25.53%) were on anti-platelet agents in combination with ACs (11 VKAs and 1 DOAC), and 8 (17%) were on no treatment. 19 (79.16%) patients on VKAs were overdosed.
Cardiac patients had a higher risk of blood transfusion 51.06% (n=24) vs 28.7% (n=95) p= 0.002, as well as ICU stay 25.53% (n=12) vs 7.55% (n=25) p=0.00.
The average length of hospital stay was higher in cardiac patients: 6 days vs. 4 days in non-cardiac patients.
The risk of recurrence was higher in cardiac patients 17% (n=8) vs 4.83% (n=16) p=0.00, as well as mortality 4.25% (n=2) vs 1.2% (n=4) p=0.002.

Conclusion

The occurrence of Gastrointestinal bleeding is more severe in the cardiac subject due to the higher morbidity and mortality compared to non-cardiac patients, hence the interest in prompt and optimal management. Patients on VKAs are at the greatest risk of Gastrointestinal bleeding , especially in the event of overdose.

Introduction

Based on the Chicago classification, HREM diagnosis is classically based on metrics obtained with wet swallows carried out in the supine position. However, both patients and physicians often feel that this is not a physiological position to conduct the test as it may not translate to the real world experience. With the patient in the upright/sitting position, the test would more closely simulate real-life behaviour and may be safer for elderly patients at risk of aspiration.

Aims & Methods

In an Asian tertiary centre, a total of 104 patients had undergone high resolution esophageal manometry (HREM) with retrospective data analysis comparing both conventional supine position with the upright position. The latter is generally favoured by all patients as this represents the physiological posture during meals.

Results

Using 2-tailed paired sample T-test, comparison across all cases showed a consistently lower median Integrated Relaxation Pressure (IRP) [6.0 mmHg vs to 8.7 mmHg; p <0.01] and lower mean Distal Contractile Integral (DCI) [1463 mmHg/cm/sec vs 1864 mmHg/cm/sec; p =0.014] in the upright posture compared to supine position although the mean Distal Latency (DL) difference was not significant [6.21secs vs 6.27 secs; p =0.491]. During upright and supine position comparison respectively, subgroup analysis on subjects with normal HREM diagnosis showed even lower median IRP [4.9 mmHg vs 7.5 mmHg; p <0.01] and lower mean DCI results [1436 mmHg/cm/sec vs 1695 mmHg/cm/sec; p <0.01] with mean DL in this subgroup showing no significant statistical difference [6.29 secs vs 6.38secs; p=0.545]. The final HREM diagnosis in upright position is concordant with the conventional supine position up to 81.7% and showed an even higher concordance in terms of management similarity up to 98.1%. Only 2 cases (2/104) showed a significant discordance between supine and upright HREM diagnosis [normal HREM vs esophagogastric juntion –outflow obstruction(EGJ-OO) and hypercontractile esophagus vs normal HREM]. Minor diagnostic discordance [normal HREM vs ineffective esophageal motility (IEM)] was noted in 17/104 cases which had no major clinical impact on patients and may be overcome by adopting a lower cut-off for mean DCI for upright group.

Conclusion

In patients who are unable to perform HREM in supine position, adopting the upright position shows a high clinical concordance and may be considered a more physiological approach in the HREM protocol.

References

Riva CG, Siboni S, Ferrari D, Sozzi M, Capuzzo M, Asti E, Ogliari C, Bonavina L. Effect of Body Position on High-resolution Esophageal Manometry Variables and Final Manometric Diagnosis. J Neurogastroenterol Motil. 2020 Jul 30;26(3):335-343. doi: 10.5056/jnm20010. PMID: 32606256; PMCID: PMC7329148.

Introduction

Individuals with disorders of brain gut interaction (DBGI) such as irritable bowel syndrome (IBS) and functional dyspepsia (FD) have symptoms that generally originate either first in the GI tract (e.g. fullness, pain: gut to brain) or brain (e.g. anxiety: brain- to –gut). It is unclear however what risk factors may moderate the order of incidence of either a DBGI or psychological diagnosis.

Aims & Methods

This study aimed to determine the proportion of individuals in general practice with a diagnosis of a DBGI (IBS and/or FD, IBS only, FD only, overlap IBS/FD) prior to a mood or anxiety disorder (gut to brain), and vice versa (brain to gut) and whether specific factors moderate the order of incidence of the diagnosis. Data was collected from a retrospective study of 152,674 patients diagnosed with a DBGI (excluding inflammatory bowel disease, coeliac disease, peptic ulcer disease, colorectal and gastric cancer) and psychological disorder (mood or anxiety disorder) at general practices in the United Kingdom over an average period of 16 years (SD=7 years). Information on which diagnosis appeared first was recorded (January 1994 to end 2022, inclusive). Multiple logistic regression was performed to compare a diagnosis of a DBGI (IBS and/or FD) first versus psychological diagnosis first on a range of sociodemographic factors (age, gender), medical conditions (allergy, eczema, Helicobacter pylori, Type 1 and Type 2 diabetes, autoimmune disease, rheumatoid arthritis, lupus, scleroderma, alcohol related diseases and prior gastrointestinal infection) and medication usage (antibiotics, proton pump inhibitors (PPI) and non-steroidal anti-inflammatory drugs (NSAIDs)) ever and prior to a diagnosis of either a DBGI or psychological disorder. Only individual moderators that reached the criterion of p<0.01 are included in the multivariate model.

Results

Of the 152,674 eligible individuals in the UK GP data set, just over half (56.2% n=85843) were diagnosed with a mood or anxiety disorder first compared with (42.9%, n=64739, 55.43%) a DBGI first. In a multivariate model being female, prior GI infection and prior PPI, antibiotic and NSAID use significantly increased the odds of being diagnosed with a DBGI first, whereas alcohol related diseases, asthma and ever having PPI and NSAID use significantly reduced the odds of having a DBGI diagnosis first (Table 1). Of clinical relevance people diagnosed with a DBGI first were twice as likely to have had prior PPI use compared with those with a psychological diagnosis first (OR=2.0, 95%CI 1.94, 2.06; P=0.000). These results were similar for IBS only, FD only and overlap DBGI.

Table 1. Multivariate model of predictors of a DBGI prior to a mood or anxiety disorder

Conclusion

In a large sample of primary care patients, prior PPI use was associated with an increased probability of a gut to brain pathway. While PPI use may indicate the presence of a upper gut DGBI, the data may equally point towards the possibility that PPI use may cause changes in the gut microbiome including reduced bacterial richness.

Introduction

Colorectal cancer (CRC) is strongly associated with iron due to the role of gut epithelium in iron uptake and the exposure of luminal epithelial cells to iron, iron trafficking within the tumour microenvironment (TM), and the role of iron in cell function including that of immune cells and tumour cells (1,2).
Tumours do not grow in isolation; they are reliant on the function of other cells within the TM (3). These cells interact with the tumour, providing tumour cells with nutrients including iron (4,5). Within the TM, monocytes are polarised into proinflammatory (M1) macrophages and alternatively activated (M2) macrophages. M1 macrophages are characterised by production of pro-inflammatory cytokines such as IL-12, production of reactive oxygen species, and activation of Th1 responses. These cells are involved in immune surveillance and anti-cancer functions. In contrast, M2 macrophages have an anti-inflammatory phenotype and tumour promotion (6). Tumour associated macrophages that resemble M2 macrophages have been shown to promote angiogenesis, matrix remodelling, and immune suppression (7,8) and have been associated with worse patient outcomes (9).
Iron may affect the tumour cells within the TM by influencing macrophage polarisation. Mice fed an iron-enriched diet increased M2 polarization of macrophages with increase in M2 markers (10). However, the situation is more complex as extravasation of red blood cells during neoangiogenesis resulting in a haemorrhagic environment repolarised the macrophages to an M1 phenotype with the ability to kill cancer cells (8). These results suggest that haemolytic RBCs and iron influence macrophage polarisation and are important players within the TM and an important focus for research in CRC.

Aims & Methods

The study aims were to determine the effects of iron treatments on the differentiation of macrophages within the TM in anaemic patients with CRC.
Normal and tumour tissues were obtained from patients in the IVICA trial (REC reference 11/EM/0237). Patients with CRC and iron deficiency anaemia were randomised to receive oral ferrous sulphate (n=20) or IV ferric carboxymaltose (n=20). Using immunofluorescence microscopy, we identified macrophages as being CD68 positive and demonstrated the expression of TLR2, suggesting that these are M1 macrophages. The pattern of M1 macrophages were confirmed with further experiments as cells that were CD68 and MHC-II (HLA-DR) positive. M2 macrophages were identified as CD68 and CD163 positive cells.

Results

Macrophages expression was significantly higher on tumour tissues from patients who received IV ferric carboxymaltose compared with oral ferrous sulphate (p<0.02). In CRC tissues, macrophages were localised as clusters mainly in the stromal tissue.
The number of M1 polarised macrophages was significantly higher in the TM of patients treated with IV ferric carboxymaltose than in those colorectal cancer patients treated with oral ferrous sulphate (p=0.01).
There was a trend towards an increase in M2 polarised macrophages in the tumour samples of those patients treated with oral iron, however, this was not significant.

Conclusion

This is the first study in humans to investigate the effect of iron treatment on the phenotype of macrophages within the TM. Data demonstrates that IV ferric carboxymaltose may increase the recruitment and / or polarisation of macrophages to an M1 phenotype within the TM in anaemic CRC patients. These results have the potential to influence patients’ management as our work suggests that IV ferric carboxymaltose may be preferable to oral ferrous sulphate.

References

1. Aksan, A. et al. (2021). Flipside of the Coin: Iron Deficiency and Colorectal Cancer. Frontiers in immunology, 12,635899.
2. Phipps, O, Brookes, MJ, Al-Hassi, HO. Iron deficiency, immunology, and colorectal cancer. Nutr Rev. 2021 Jan1;79(1):88-97
3. Torti SV, Torti FM. Iron and cancer: more ore to be mined. Nat Rev Cancer. 2013;13:342–355.
4. Duan, X et al. Tumor associated macrophages deliver iron to tumor cells via Lcn2. Int J Physiol Pathophysiol Pharmacol 2018;10:105–14
5. Pollard, JW. Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer. 2004 Jan;4(1):71-8.
6. Mills, CD et al.. A Breakthrough: Macrophage-Directed Cancer Immunotherapy. Cancer Res 2016;76:513–6
7. Chanmee, T et al. Tumor-associated macrophages as major player in the tumor microenvironment. Cancers. 2014;6:1670–1690.
8. Costa da Silva, M et al. Iron Induces Anti-tumor Activity in Tumor-Associated Macrophages. Front Immunol. 2017;8:1479.
9. Tang, X. Tumor-associated macrophages as potential diagnostic and prognostic biomarkers in breast cancer. Cancer Lett. 2013 May10;332(1):3-10.
10. Agoro, R et al. Cell iron status influences macrophage polarization. PLoS One 2018;13:e0196921

Clinical Case Summary

A 25-year-old man, a law graduate, denied significant medical history, except for an appendectomy in 2014. He was diagnosed with chronic idiopathic ulcerative colitis in 2016 and was previously treated with mesalazine 4.5g every 24 hours. A colonoscopy in 2019 showed pancolitis Mayo 3 (Montreal S2-E3). Due to the lack of response to conventional treatment, prednisone cycles were initiated, and infliximab was started at a dose of 5mg/kg since 2019 with an adequate clinical response. On 12/24/2020, calprotectin was 5149 mcg/g.
In September 2021, he presented with asthenia, adynamia, dizziness, and unquantified fever, so he went to the hospital, where systemic inflammatory response syndrome was evident (tachycardia, fever of 39°C, and leukocytosis, dyspnea). Serial blood cultures and bacilloscopies were negative, and a chest CT scan showed a solid nodule-like pulmonary lesion in the right middle lobe (image 1). In November 2021, a thoracotomy with right middle lobectomy was performed, revealing abundant purulent material and a suggestive lesion of a lung abscess; it was positive for Nocardia farcinica, and histopathological results were positive for Nocardia spp. The patient subsequently developed cerebellar syndrome, and an MRI on November 5, 2021, showed cerebellar abscesses in the left hemisphere and hydrocephalus (image 1), requiring a ventriculoperitoneal shunt placement and surgical decompression, draining abscess, and isolating Nocardia spp.
Directed antibiotic therapy (trimethoprim-sulfamethoxazole) was started and continued until December 2021 with clinical improvement. Anti-TNF was discontinued, and mesalazine, steroid, and azathioprine were continued to maintain clinical remission of the disease without neurological and respiratory sequelae.

References

1. Abreu C, Rocha-Pereira N, Sarmento A, Magro F. Nocardia infections among immunomodulated inflammatory bowel disease patients: A review. World J Gastroenterol. 2015 Jun 7;21(21):6491-8. Doi: 10.3748/wjg.v21.i21.6491. PMID: 26074688; PMCID: PMC4458760.
2. Margalit I, Goldberg E, Ben Ari Y, Ben-Zvi H, Shostak Y, Krause I, Muhsen K. Clinical correlates of nocardiosis. Sci Rep. 2020 Aug 31;10(1):14272. Doi: 10.1038/s41598-020-71214-4. PMID: 32868850; PMCID: PMC7459281.
3. Garner O, Ramirez-Berlioz A, Iardino A, Mocherla S, Bhairavarasu K. Disseminated Nocardiosis Associated with Treatment with Infliximab in a Patient with Ulcerative Colitis. Am J Case Rep. 2017 Dec 21;18:1365-1369. Doi: 10.12659/ajcr.906391. PMID: 29263313; PMCID: PMC5742452.

Disclosure

Patients with Inflammatory Bowel Disease (IBD) undergoing anti-TNFa treatment are at risk of opportunistic infections, including nocardiosis, caused by Nocardia, gram-positive bacteria that can cause local (lung, skin, and brain) or disseminated infections. In the literature, only 11 cases of nocardiosis related to anti-TNFa have been reported¹.TNFa is an important mediator of inflammation for granuloma formation, and Nocardia spp. is one of the pathogens that generate these granulomas². The diagnosis of nocardiosis should have a high clinical suspicion, especially in patients with risk factors, as it is one of the least reported opportunistic infections, in our case, with the use of anti-TNF in the context of IBD. There are no official reports on prevalence and incidence in the literature².
The most frequent sites of dissemination are the lungs and skin, leading to the central nervous system and any organ³. The diagnostic confirmation is made through pathogen isolation in a clinical sample, which was performed through histopathology of a pulmonary segment².
Treatment is based on antimicrobial therapy and restoration of complications, in our case, a segmentectomy was necessary due to pulmonary infection, and a ventriculoperitoneal shunt placement was necessary due to central nervous system involvement. TMP/SMX has been considered the first-line antimicrobial for 50 years², but targeted therapy based on isolation is recommended, with alternatives including amikacin, carbapenems, and third-generation cephalosporins². The response to TMP/SMX was appropriate in this case.