A computational pipeline for identifying gene targets and signalling pathways in cancer cells to improve lymphocyte infiltration and immune checkpoint therapy efficacy.

BACKGROUND: Tumour-infiltrating lymphocytes (TILs) are crucial for effective immune checkpoint blockade (ICB) therapy in solid tumours. However, ∼70% of these tumours exhibit poor lymphocyte infiltration, rendering ICB therapies less effective. METHODS: We developed a bioinformatics pipeline integrating multiple previously unconsidered factors or datasets, including tumour cell immune-related pathways, copy number variation (CNV), and single tumour cell sequencing data, as well as tumour mRNA-seq data and patient survival data, to identify targets that can potentially improve T cell infiltration and enhance ICB efficacy. Furthermore, we conducted wet-lab experiments and successfully validated one of the top-identified genes. FINDINGS: We applied this pipeline in solid tumours of the Cancer Genome Atlas (TCGA) and identified a set of genes in 18 cancer types that might potentially improve lymphocyte infiltration and ICB efficacy, providing a valuable drug target resource to be further explored. Importantly, we experimentally validated SUN1, which had not been linked to T cell infiltration and ICB therapy previously, but was one of the top-identified gene targets among 3 cancer types based on the pipeline, in a mouse colon cancer syngeneic model. We showed that Sun1 KO could significantly enhance antigen presentation, increase T-cell infiltration, and improve anti-PD1 treatment efficacy. Moreover, with a single-cell multiome analysis, we identified subgene regulatory networks (sub-GRNs) showing Stat proteins play important roles in enhancing the immune-related pathways in Sun1-KO cancer cells. INTERPRETATION: This study not only established a computational pipeline for discovering new gene targets and signalling pathways in cancer cells that block T-cell infiltration, but also provided a gene target pool for further exploration in improving lymphocyte infiltration and ICB efficacy in solid tumours. FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

Effectiveness of smoking cessation interventions for smokers with Crohn's disease: a systematic review.

Aims: Smoking cessation (SC) in Crohn's disease (CD) is widely accepted to be the most important modifiable factor to improve outcomes in these patients. We aimed in this review to provide a summary of the evidence base regarding the effectiveness of SC interventions in patients with CD. Materials & methods: The following databases were systematically searched from inception to February 2022: PubMed, Google Scholar and Cochrane Library. Results: Overall, five articles met the research criteria. Studies sample size ranged from 17 to 474 patients. At the outcome level, the abstinence rates ranged from 14.8 to 42% and was ≤25% in four studies. The three studies with control groups did not report statistically higher SC rates in the intervention groups. No predictors of interventions success were identified in this review. Conclusion: Implementation and evaluation of tailored SC interventions for CD patients must be promptly addressed in further studies.

Exploring work productivity loss in patients with inflammatory bowel disease.

Aim: We aimed in this study to evaluate the impact of inflammatory bowel disease (IBD) on patients' professional life and to determine predictors of severe work productivity loss (WPL). Materials & methods: A cross sectional study including patients with a confirmed diagnosis of IBD. Work productivity was evaluated with the work productivity and activity impairment score. Results: Severe absenteeism and WPL were found in respectively 7 (5.1%) and 54 (39.1%) patients. In multivariate analysis, the following features were found to be independently associated with severe WPL: penetrating Crohn's disease (p: 0.001, OR: 6), anemia (p: 0.031, OR: 3.23), diarrhea (p < 0.001, OR: 11.23) and a secondary level of education (p: 0.003, OR: 1.95). Conclusion: Our results show that IBD have a substantial effect on patients' professional life.

Inflammatory bowel diseases (IBD) are chronic conditions that cause inflammation in the digestive system. We wanted to know how IBD affects people's ability to work and what factors contribute to work difficulties. We asked adults with IBD about their education, work conditions and medical history. We found that a significant number of patients experience severe work productivity loss and absenteeism. Factors such as certain types of IBD, anemia, diarrhea and lower education level were linked to more severe work problems. These findings emphasize the impact of IBD on work life and highlight the importance of addressing these challenges in patient care.

Recurrent primary hepatic VIPoma treated with a combination of surgical resection and loco-regional therapy.

Vasoactive intestinal peptide (VIP) secreting tumors (VIPomas) are insidious functional neuroendocrine tumors originating mainly from pancreatic islet cells. Hepatic localization is considered exceedingly rare as only few cases have been reported in the literature. Diagnostic and therapeutic management of this tumor is still not clearly codified and therefore represents a real challenge for clinicians. Herein we report a unique case of a primary hepatic VIPoma recurrence in a female patient 22 years after curative resection. The patient had two sessions of transarterial chemoembolization. Complete symptomatic improvement was achieved since the first day after the first session. This case highlights that long-term follow-up for patients with hepatic VIPoma is mandatory as recurrence could occur several years after curative surgical treatment.

VIPomas are rare tumors secreting a hormone that is vasoactive in the intestine causing severe diarrhea. The majority of VIPomas arise within the pancreas. The hepatic localization is extremely rare. We report a case of a very late recurrence of a primary hepatic VIPoma surgically treated 20 years ago. The case was managed with therapeutic radiology by blocking the blood supply to the tumors after administering anticancer drugs in the vessels near them.

Esophageal hirudiniasis: an unusual cause of upper gastrointestinal bleeding.

Leeches are carnivorous, hermaphroditic, segmented worms mainly found in fresh water. The majority of leech attachments are external and short-lasting. Internal surfaces can be involved. Yet, esophageal attachment is very rare. We report a case of a 59-year-old female who presented with hematemesis, melena and chest pain. Upper gastrointestinal endoscopy revealed a round black foreign body in the mid-third of the esophagus identified as a leech. We carefully extracted the worm with a forceps applied to the middle of its body. The diagnosis of leech infestation should be kept in mind when exploring gastrointestinal bleeding in patients living in rural areas and those with poor living conditions.

Spleen metastases secondary to gastric neuroendocrine carcinoma: case report.

Neuroendocrine carcinoma (NEC) in the stomach represents a rare and rapidly growing type of gastric tumors. They are considered a distinct entity of neuroendocrine tumors characterized by an aggressive behavior and high metastases rate. On the other hand, spleen metastases of neuroendocrine tumors are extremely rare. We report the first case of spleen metastases of gastric neuroendocrine carcinoma. The patient was a 54-year-old male who presented with a 10-month history of epigastralgia. Upper gastro-intestinal endoscopy revealed a 5 cm ulcerative lesion located in the greater gastric curvature. Biopsies with immunohistochemical staining revealed gastric neuroendocrine carcinoma. Abdominal computed tomography showed thickening of the stomach with two large solid spleen lesions. Abdominal Magnetic Resonance Imaging and 18-fluorodexyglucose positron-emission tomography revealed peritoneal carcinosis and splenic metastases with splenic vein invasion. Clinicians should keep in mind that splenic metastases can arise from gastric neuroendocrine tumors (NETs).

Massive hematochezia due to jejunal varices successfully treated with coil embolization.

We report a case of hematochezia with hemodynamic instability due to jejunal varices in a cirrhotic patient with no prior history of surgery. The patient was managed with coil embolization via the portal vein. After which, the patient did not present any hemorrhage recurrence and maintained a stable hemoglobin level.

Osteopetrosis: a rare case of portal hypertension.

Osteopetrosis is a rare genetic bone disorder characterized by a defect in osteoclasts recruitment and function. Its manifestations are numerous and they mainly include skeletal and dental deformities, cranial nerve entrapment and infections. Over time, osteoclastic expansion invades bone marrow leaving little space for hematopoietic cells. As a result, extramedullary hematopoiesis takes place in the reticular system mainly in the spleen and liver. In these patients, portal hypertension can occur as a result of extramedullary hematopoiesis associated splenomegaly. We are reporting in this article a rare case of spontaneous bacterial peritonitis associated with portal hypertension in a patient with osteopetrosis.