Mesenchymal stem cells and their potential therapeutic benefits and challenges in the treatment and pathogenesis of gastric cancer.

Mesenchymal stem/stromal cells (MSCs) are acknowledged for their remarkable ability to undergo differentiation into various cell types. In addition, they exhibit anti-tumor characteristics, prompting endeavors to modify MSCs for employment in cancer therapies. On the contrary, it is imperative to recognize that MSCs have been extensively linked to pathways that facilitate the advancement of tumors. Numerous research studies have sought to modify MSCs for clinical application; however, the outcomes have been ambiguous, potentially due to the heterogeneity of MSC populations. Furthermore, the conflicting roles of MSCs in suppressing and promoting tumor growth present a challenge to the appropriateness of their use in anti-cancer therapies. Currently, there exists a lack of comprehensive comprehension concerning the anti-tumor and pro-tumor characteristics of MSCs for gastric cancer (GC). This article discusses the influence of MSCs on GC, the underlying mechanisms, the origins of MSCs, and their effects. This review article also elucidates how MSCs exhibit dual characteristics of promoting and inhibiting tumor growth. Hence, it is of utmost importance that clinical inquiries aimed at utilizing MSCs as a therapeutic intervention for cancer consider the potentiality of MSCs to accelerate the progression of GC. It is crucial to exercise caution throughout the process of developing MSC-based cellular therapies to enhance their anti-cancer attributes while simultaneously eliminating their tumor-promoting impacts.

Interleukin-6 serves as a critical factor in various cancer progression and therapy.

Interleukin-6 (IL-6), a pro-inflammatory cytokine, plays a crucial role in host immune defense and acute stress responses. Moreover, it modulates various cellular processes, including proliferation, apoptosis, angiogenesis, and differentiation. These effects are facilitated by various signaling pathways, particularly the signal transducer and activator of transcription 3 (STAT3) and Janus kinase 2 (JAK2). However, excessive IL-6 production and dysregulated signaling are associated with various cancers, promoting tumorigenesis by influencing all cancer hallmarks, such as apoptosis, survival, proliferation, angiogenesis, invasiveness, metastasis, and notably, metabolism. Emerging evidence indicates that selective inhibition of the IL-6 signaling pathway yields therapeutic benefits across diverse malignancies, such as multiple myeloma, prostate, colorectal, renal, ovarian, and lung cancers. Targeting key components of IL-6 signaling, such as IL-6Rs, gp130, STAT3, and JAK via monoclonal antibodies (mAbs) or small molecules, is a heavily researched approach in preclinical cancer studies. The purpose of this study is to offer an overview of the role of IL-6 and its signaling pathway in various cancer types. Furthermore, we discussed current preclinical and clinical studies focusing on targeting IL-6 signaling as a therapeutic strategy for various types of cancer.

Application of mesenchymal stem cells derived from the umbilical cord or Wharton's jelly and their extracellular vesicles in the treatment of various diseases.

Mesenchymal stem cells (MSCs) originating from the umbilical cord (UC) or Wharton's jelly (WJ) have attracted substantial interest due to their potential to augment therapeutic approaches for a wide range of disorders. These cells demonstrate a wide range of capabilities in the process of differentiating into a multitude of cell types. Additionally, they possess a significant capacity for proliferation and are conveniently accessible. Furthermore, they possess a status of being immune-privileged, exhibit minimal tumorigenic characteristics, and raise minimal ethical concerns. Consequently, they are well-suited candidates for tissue regeneration and the treatment of diseases. Additionally, UC-derived MSCs offer a substantial yield compared to other sources. The therapeutic effects of these MSCs are closely associated with the release of nanosized extracellular vesicles (EVs), including exosomes and microvesicles (MVs), containing lipids, microRNAs, and proteins that facilitate intercellular communication. Due to their reduced tumorigenic and immunogenic characteristics, in addition to their convenient manipulability, EVs have arisen as a viable alternative for the management of disorders. The favorable characteristics of UC-MSCs or WJ-MSCs and their EVs have generated significant attention in clinical investigations encompassing diverse pathologies. Therefore, we present a review encompassing current preclinical and clinical investigations, examining the implications of UC-MSCs in diverse diseases, including those affecting bone, cartilage, skin, liver, kidney, neural, lung, cardiovascular, muscle, and retinal tissues, as well as conditions like cancer, diabetes, sepsis, and others.

Air embolism complicating endoscopic retrograde cholangiopancreatography.

Aim: Venous air embolism is a rare but potentially life threatening complication of endoscopic retrograde cholangiopancreatography. Diagnosis is difficult because of the lack of specific signs or symptoms. Case: A 62-year-old man underwent endoscopic retrograde cholangiopancreatography for choledocholithiasis. A cardiovascular collapse occurred during the procedure. The echocardiography showed air within the right ventricle. Aspiration of air from the right ventricle was done and saved the patient's life. Conclusion: We highlight through this case that increased awareness is essential for prompt recognition of the air embolism to allow life-saving therapy.

Endoscopic treatment is the first-line treatment for biliary stones. It may be associated with various complications. We report the case of a 62-year-old patient who underwent endoscopic treatment for biliary stone. During the procedure, he experienced disturbed cardiac function due to the passage of air bubbles into the cardiac cavities. The bubbles were aspirated with a good outcome.

Thyroid storm-induced acute liver dysfunction and portal hypertension in a patient with Graves' disease: a case report.

Thyroid storm is a life-threatening condition associated with multiorgan dysfunction and decompensation. We report the case of a 41-year-old woman having Graves' disease presented with thyroid storm complicated with liver dysfunction and portal hypertension in the absence of congestive heart failure or known liver disease. After successful therapeutic management, all biological, clinical and morphological abnormalities regressed.

Graves' disease is an immune system disorder that results in the overproduction of thyroid hormones. We report the case of a 41-year-old woman with Graves' disease who presented with reversible liver dysfunction and high blood pressure in the portal vein (located in the abdomen) following the withdrawal of her treatment.

Dual role of mesenchymal stem/stromal cells and their cell-free extracellular vesicles in colorectal cancer.

Colorectal cancer (CRC) is one of the main causes of cancer-related deaths. However, the surgical control of the CRC progression is difficult, and in most cases, the metastasis leads to cancer-related mortality. Mesenchymal stem/stromal cells (MSCs) with potential translational applications in regenerative medicine have been widely researched for several years. MSCs could affect tumor development through secreting exosomes. The beneficial properties of stem cells are attributed to their cell-cell interactions as well as the secretion of paracrine factors in the tissue microenvironment. For several years, exosomes have been used as a cell-free therapy to regulate the fate of tumor cells in a tumor microenvironment. This review discusses the recent advances and current understanding of assessing MSC-derived exosomes for possible cell-free therapy in CRC.

Impact of direct-acting antiviral on subclinical atherosclerosis in chronic hepatitis C infected patients.

INTRODUCTION: The impact of direct antiviral drugs (DAAs) on extrahepatic manifestations in chronic hepatitis C (CHC) has been poorly studied. AIM: To assess the prevalence of subclinical atherosclerosis in patients with CHC and the impact of DAAs on atherosclerotic lesions. Methods A 5-year prospective evaluative study, including patients followed for CHC at hepato-gastroenterology department. The subclinical atherosclerosis was assessed by ultrasound measurement of carotid intima-media thickness (IMTc) and the highest IMTc measurements from the left and right side defined the IMTc maximum (IMTc max). IMTc>75th percentile (IMTc75) define subclinical atherosclerosis with high cardiovascular risk. Patients were evaluated before (T0) and one year after DAAs therapy achievement (T1). RESULTS: At time T0, forty patients (median age: 55 y.; sex ratio M / F = 0.48), were included. Average value of IMTc max was 0.68 ± 0.16 mm. Subclinical atherosclerosis was noted in 82.5 %. At time T1, 28 patients were evaluated, all of whom completed sustained virological response (SVR). Compared to time T0, there was a significant increase in cholesterol (p = 0.001) and triglyceride (p = 0.009) levels. IMTc max was significantly higher at time T1 compared to T0 (0.75 Vs 0.67 mm, p = 0.04). Prevalence of IMTc75 was 82.1% at time T0 and 75% at time T1 (p=0.5). CONCLUSIONS: SVR, in CHC patients treated with DAA, was associated with worsening of carotid atherosclerotic lesions.

A rare cause of spontaneous hemoperitoneum: intra-abdominal vein rupture.

Aim: Ruptures of the intra-abdominal vein causing a spontaneous hemoperitoneum in cirrhotic patients is a rare condition. However, diagnosis must be considered early in cirrhotic patients with hematic ascites as a delayed diagnosis with hemodynamic instability is associated with a poor prognosis. Case report: We present the case of a 54-year-old cirrhotic patient who presented a spontaneous hemoperitoneum due to the rupture of the intra-abdominal vein that was diagnosed during exploratory laparoscopy. Conclusion: Early diagnosis and management of spontaneous hemoperitoneum due to the rupture of intra-abdominal vein helps improve its prognosis.

Spontaneous hemoperitoneum is a rare but catastrophic condition caused by the rupture of the liver, spleen or abdominal vessels. In patients with cirrhosis, diagnosis of spotaneous hemoperitoneum is difficult. This is a case report of a 54-year-old cirrhotic man with a spontaneous hemoperitoneum due to the rupture of a vein within the abdomen. The diagnosis was suspected as the patient had signs of blood in the abdomen. To confirm spontaneous hemoperitoneum, the doctors performed a procedure called exploratory laparoscopy, which involves inserting a small camera into the abdomen. The laparoscopy confirmed the presence of blood and thus the diagnosis of spontaneous hemoperitoneum.

A rare case of gastric metastasis originating from primary lung adenocarcinoma: a case report.

Unlike liver and lung, the stomach is rarely a metastatic location for cancers. We report a case of a 62-year-old man known to have lung adenocarcinoma poorly differentiated presented with melena 1 month after diagnosis. Upper endoscopy revealed an ulcerated tumor in the prepyloric antrum. The diagnosis of gastric metastasis from pulmonary cancer was confirmed by the immunohistochemical staining for the thyroid transcriptional factor-1 and the pattern cytokeratine CK7+/CK20-. In conclusion, gastric metastasis from primary lung cancer is a rare phenomenon that every clinician must keep in mind.

A 62-year-old man known to have lung adenocarcinoma poorly differentiated presented with melena 1 month after diagnosis. Upper endoscopy revealed an ulcerated tumor in the prepyloric antrum. The diagnosis of gastric metastasis from pulmonary cancer was confirmed by histology.

Synchronous primary gastric and renal tumors: a case report.

Synchronous multiple primary cancers of the stomach and kidney are very rare, only 45 cases of synchronous multiple primary cancers of the stomach and kidney had been reported in the literature up until 2020. Thus far, no particular risk factors have been identified. We present a case of synchronous multiple primary cancers of the stomach and kidney in a 67-year-old female presenting with a 3-month history of vomiting and abdominal pain. The diagnosis of gastric adenocarcinoma with signet ring cells was confirmed through upper endoscopy with biopsies, while CT-guided biopsies of the renal tumor confirmed the diagnosis of primary kidney neoplasm.

Having more than one cancer at the same time is known as multiple primary malignancies. Having cancers in both the stomach and kidney at the same time is even rarer, with only 45 cases reported in literature. The exact causes of such cancers occurring together are not yet known. We present a 67-year-old woman who was diagnosed with synchronous multiple primary cancers of the stomach and kidney. She presented with vomiting and abdominal pain. The diagnosis of gastric cancer was confirmed through upper endoscopy with biopsies, while biopsies of the renal tumor confirmed the diagnosis of primary kidney cancer.

Genetically engineered neural stem cells (NSCs) therapy for neurological diseases; state-of-the-art.

Neural stem cells (NSCs) are multipotent stem cells with remarkable self-renewal potential and also unique competencies to differentiate into neurons, astrocytes, and oligodendrocytes (ODCs) and improve the cellular microenvironment. In addition, NSCs secret diversity of mediators, including neurotrophic factors (e.g., BDNF, NGF, GDNF, CNTF, and NT-3), pro-angiogenic mediators (e.g., FGF-2 and VEGF), and anti-inflammatory biomolecules. Thereby, NSCs transplantation has become a reasonable and effective treatment for various neurodegenerative disorders by their capacity to induce neurogenesis and vasculogenesis and dampen neuroinflammation and oxidative stress. Nonetheless, various drawbacks such as lower migration and survival and less differential capacity to a particular cell lineage concerning the disease pathogenesis hinder their application. Thus, genetic engineering of NSCs before transplantation is recently regarded as an innovative strategy to bypass these hurdles. Indeed, genetically modified NSCs could bring about more favored therapeutic influences post-transplantation in vivo, making them an excellent option for neurological disease therapy. This review for the first time offers a comprehensive review of the therapeutic capability of genetically modified NSCs rather than naïve NSCs in neurological disease beyond brain tumors and sheds light on the recent progress and prospect in this context.

Multifocal nodular lesions in fatty liver mimicking neoplastic disease: a case report.

Usually, fatty hepatic infiltration is diffuse and homogeneous. However, in some cases, it can be localized simulating benign or malignant tumors. We present a case of a 61-year-old female patient with family history of malignancy: sister with lung cancer, an other sister with colon cancer and a mother with breast cancer; who presented with multiple hepatic nodules at the ultrasonography images. CT scan and MRI were not sufficient to pose a certain diagnosis which was later confirmed by liver biopsy.

In some cases, fatty hepatic infiltration may simulate benign or malignant tumors. We present a case of a 61-year-old female patient with family history of malignancy who presented with multiple hepatic nodules at the ultrasonography images. CT scan and MRI were not sufficient to pose a certain diagnosis which was later confirmed by liver biopsy.

Performance of the ADRESS-HCC score in the assessment of the risk of hepatocellular carcinoma in viral cirrhosis in Tunisia.

INTRODUCTION: The ADRESS-HCC score allows predicting the risk of occurrence of Hepatocellular carcinoma in cirrhosis at one year of follow-up. AIM: Measuring the performance of ADRESS-HCC in predicting the risk of degeneration on post-viral cirrhosis, in a gastroenterology department in Tunisia. METHODS: Retrospective study, including patients followed for compensated viral cirrhosis in the gastroenterology department of the Mohamed Taher Maamouri hospital. The ADRESS-HCC score was calculated at diagnosis of cirrhosis. We divided patients into two groups depending on whether they developed Hepatocellular carcinoma or not. We evaluated the performance of the ADRESS-HCC score in predicting the risk of Hepatocellular carcinoma according to a threshold value. RESULTS: We enrolled 60 patients; the mean age was 62 years. Twenty-five patients developed hepatocellular carcinoma during follow-up. The mean value of ADRESS-HCC score was 5.08. To predict the occurrence of hepatocellular carcinoma at 1 year of follow-up, the area under the curve of the ADRESS-HCC score was 0.74 (p=0.01). For a threshold value of 5.63 its sensitivity was 91 % with a negative predictive value of 95.83%. CONCLUSION: The ADRESS-HCC score had an average performance in predicting degeneration in post-viral cirrhosis.

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.

A case of gastric metastasis originating from right-sided colon cancer 4 years after colectomy.

The stomach is rarely a metastatic site of other primary cancers. Gastric metastasis from colonic cancer is exceptional. We hereby report a case of a 54-year-old male patient who underwent a right hemicolectomy for right-sided colon cancer. The pathology exam revealed well differentiated adenocarcinoma, it was classified stage IIb. Regular controls performed including colonoscopy were normal. Four years after colectomy, the patient was admitted for hematemesis with epigastric pain with detoriation of general condition . Gastroscopy revealed a large ulceroproliferative mass in the antropyloric region. Histology showed that this tumor was an adenocarcinoma similar to the primary right colon cancer, which led to the diagnosis of metastatic gastric cancer originating from colon cancer.

[Predictors of hepatic encephalopathy in patients with severe acute liver injury]. / Facteurs prédictifs de l'encéphalopathie hépatique au cours de l'atteinte hépatique aiguë sévère.

Introduction: severe acute liver injury (SALI) formerly known as severe acute hepatitis is an acute inflammation of the liver with markers of liver injury (elevated transaminases) and signs of hepatocellular failure (jaundice and INR greater than 1.5) according to the latest definition of the European Association for the Study of the Liver (EASL). An important prognostic factor in SALI is the development of hepatic encephalopathy (HE) and thus its progression to acute liver failure (ALF), formerly known as acute severe hepatitis. The purpose of this study is to investigate factors predicting the development of hepatic encephalopathy during SALI. Methods: we conducted a retrospective study of patients treated for SALI between January 2000 and December 2019. We divided patients into two groups depending on whether hepatic encephalopathy occurred. We performed an analytical study comparing the two groups according to their epidemiological, biological and evolutionary data. Results: data from the medical records of fifty-nine patients were collected. A virus was the most frequent cause (63%). Hepatic encephalopathy occurred in 15 patients (25.4%). Factors predicting the development of HE in univariate analysis were a delay in consultation of more than 9 days, an INR level of more than 2.45, a bilirubin level of more than 230 µmol/l, creatinine greater than 60.5 µmol/l, urea greater than 5.5 mmol/l and MELD score greater than 26.5 (p=0.023, p=0.017, p=0.0001, p=0.049, p=0.0001, p=0.0001 respectively). Autoimmune hepatitis and an undetermined cause were associated with the development of HE (p=0,003 and p=0,044, respectively). In multivariate analysis, autoimmune aetiology and a urea level above 5.5 mmol/l were significantly associated with the occurrence of HE. No statistically significant differences were found between the two groups with regard to age, sex and diabetes. Conclusion: SALI is a rare disease, mainly due to a virus in our country. Predictive factors of HE are important for early identification of patients at risk of adverse outcomes.

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).

Post-chemotherapy Gastric Obstruction in Diffuse Large B-Cell Lymphoma: Endoscopic Dilation Can Fix It!

Treatment of diffuse large B-cell lymphoma (DLBCL) is based on immunochemotherapy with overall good outcomes. Complications related to the treatment or the disease itself can occur during follow-up. We herein report a case of a 37-year-old male who was diagnosed with stage IV gastric DLBCL. Subsequently, he underwent R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone) chemotherapy. After six cycles of treatment, complete remission has been achieved. But afterwards, the patient presented with a symptomatic gastric obstruction related to a tight stenosis in the antro-fundic junction. Endoscopic dilation was performed and multiple macrobiopsies within the stenosis were taken. Pathological examination concluded to the fibrous character of the stricture. In cases of post-chemotherapy obstruction in gastric DLBCL, endoscopic treatment should be attempted carefully in patients with no evidence of active lymphoma. Diagnosis of fibrosis can avoid surgery and its morbidity.

Study of the relationship between FT3, FT4, and TSH with bone resorption indices in men with hypothyroidism.

AIM: This study aimed to find the effect of hypothyroidism in men on metabolism and bone mineral density. METHOD: The study included a patients group of 90 men suffering from hypothyroidism and 120 healthy subjects as a control group. The study comprised the estimation of the concentration of Blood free triiodothyronine (FT3), free thyroid hormone (FT4), thyroid stimulating hormone (TSH), bone resorption index type I collagen C-terminal peptide (CTX-1), the serum calcium (Ca2+), serum phosphorus (Pi3+), the bone mineral density of the lumbar spine and femoral neck. RESULTS: In the hypothyroidism men group: (1) the bone mass was lower than the control group with significant differences, (2) the bone resorption index CTX-1 was significantly higher than that in the control group and calcium and phosphorus were not different from those in healthy control subjects, and (3) TSH was positively correlated with CTX-1. Male TSH and CTX-1 levels were positively correlated. CONCLUSIONS: There is bone loss in men with hypothyroidism, which may be related to increased bone resorption.

Esophageal tuberculosis as an unusual cause of dysphagia: a case report.

Esophageal tuberculosis is a rare cause of infectious esophagitis, even in countries with endemic tuberculosis. This impairment is often secondary. We report a case of secondary esophageal tuberculosis in an immunocompetent patient, clinically revealed by dysphagia. Esophagogastroduodenoscopy showed a large ulcer in the middle third of the esophagus with a fistula opening in the center of the ulcer. Histopathological examination of multiple esophageal tissue biopsies revealed epithelioid cell granulomas without caseous necrosis. We completed with Computed Tomography (CT) scan of the chest which revealed a fistula of the middle third of the esophagus, multiple mediastinal necrotic adenopathies and diffuse pulmonary micronodules suggesting miliary tuberculosis. Sputum examination for acid-fast-bacilli was positive. Anti-tuberculosis treatment resulted in a good response with complete remission. It is therefore important to recognize and include this entity in the differential diagnosis of patients with dysphagia particularly in countries with a high incidence of tuberculosis.