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Journal For Immunotherapy of Cancer Dec 2022The immunogenic nature of metastatic colorectal cancer (CRC) with high microsatellite instability (MSI-H) underlies their responsiveness to immune checkpoint blockade...
BACKGROUND
The immunogenic nature of metastatic colorectal cancer (CRC) with high microsatellite instability (MSI-H) underlies their responsiveness to immune checkpoint blockade (ICB). However, resistance to ICB is commonly observed, and is associated with the presence of peritoneal-metastases and ascites formation. The mechanisms underlying this site-specific benefit of ICB are unknown.
METHODS
We created a novel model for spontaneous multiorgan metastasis in MSI-H CRC tumors by transplanting patient-derived organoids (PDO) into the cecum of humanized mice. Anti-programmed cell death protein-1 (PD-1) and anti-cytotoxic T-lymphocytes-associated protein 4 (CTLA-4) ICB treatment effects were analyzed in relation to the immune context of primary tumors, liver metastases, and peritoneal metastases. Immune profiling was performed by immunohistochemistry, flow cytometry and single-cell RNA sequencing. The role of B cells was assessed by antibody-mediated depletion. Immunosuppressive cytokine levels (interleukin (IL)-10, transforming growth factor (TGF)b1, TGFb2, TGFb3) were determined in ascites and serum samples by ELISA.
RESULTS
PDO-initiated primary tumors spontaneously metastasized to the liver and the peritoneum. Peritoneal-metastasis formation was accompanied by the accumulation of ascites. ICB completely cleared liver metastases and reduced primary tumor mass but had no effect on peritoneal metastases. This mimics clinical observations. After therapy discontinuation, primary tumor masses progressively decreased, but peritoneal metastases displayed unabated growth. Therapy efficacy correlated with the formation of tertiary lymphoid structures (TLS)-containing B cells and juxtaposed T cells-and with expression of an interferon-γ signature together with the B cell chemoattractant CXCL13. B cell depletion prevented liver-metastasis clearance by anti-CTLA-4 treatment. Peritoneal metastases were devoid of B cells and TLS, while the T cells in these lesions displayed a dysfunctional phenotype. Ascites samples from patients with cancer with peritoneal metastases and from the mouse model contained significantly higher levels of IL-10, TGFb1, TGFb2 and TGFb3 than serum samples.
CONCLUSIONS
By combining organoid and humanized mouse technologies, we present a novel model for spontaneous multiorgan metastasis by MSI-H CRC, in which the clinically observed organ site-dependent benefit of ICB is recapitulated. Moreover, we provide empirical evidence for a critical role for B cells in the generation of site-dependent antitumor immunity following anti-CTLA-4 treatment. High levels of immunosuppressive cytokines in ascites may underlie the observed resistance of peritoneal metastases to ICB.
Topics: Mice; Animals; Immune Checkpoint Inhibitors; Transforming Growth Factor beta3; Peritoneum; Ascites; Peritoneal Neoplasms; Cytokines; Liver Neoplasms; Colorectal Neoplasms
PubMed: 36543378
DOI: 10.1136/jitc-2022-005345 -
Frontiers in Endocrinology 2023Obesity is detrimental to infertility. The association between weight-adjusted-waist index (WWI, a recently developed adiposity indicator) and infertility has not...
AIMS
Obesity is detrimental to infertility. The association between weight-adjusted-waist index (WWI, a recently developed adiposity indicator) and infertility has not previously been confirmed.
METHODS
The data for this study were obtained from the National Health and Nutrition Examination Survey (NHANES) 2013-2018. Each participant's WWI was calculated as their waist circumference in centimeters by the square root of weight in kilograms. Multivariable logistic regression and generalized additive model were utilized to investigate the relationship between WWI with infertility. We used smoothed curve fitting to explore the non-linear relationship. Subgroup analysis and interaction tests were also conducted.
RESULTS
A total of 3,526 participants with ages from18 to 45 were enrolled, 364 of whom were infertile. With the higher WWI, infertility was more prevalent (OR = 1.42, 95% CI: 1.22-1.65), and this association was still consistent in subgroups (all P for interaction> 0.05). Smoothed curve fitting showed a positive non-linear relationship between WWI and infertility. Furthermore, we discovered that WWI had a stronger connection with the risk of infertility than other markers of obesity including WC, body mass index (BMI) and a body shape index (ABSI).
CONCLUSIONS
Weight-adjusted-waist index levels were positively linked to an increased risk of infertility in American females and showed a stronger association than other markers of obesity. Our research indicated WWI could help identify women with infertility, and managing obesity as determined by WWI may help to reduce the risk of infertility.
Topics: Female; Humans; Infertility, Female; Nutrition Surveys; Research; Abdomen; Obesity
PubMed: 37614708
DOI: 10.3389/fendo.2023.1175394 -
The American Surgeon Sep 2022The mesentery is a common site of metastasis from gastrointestinal, pancreatic, and biliary cancers. Primary mesenteric cancers are rare and usually mesenchymal and...
The mesentery is a common site of metastasis from gastrointestinal, pancreatic, and biliary cancers. Primary mesenteric cancers are rare and usually mesenchymal and benign. Mesenteric leiomyosarcoma is a rare, malignant smooth muscle sarcoma with an incidence of 1:350000. It usually arises from the vasculature of the mesentery. The ileum of the small bowel is the most common site of origin. Due to its low incidence, preoperative diagnosis is difficult. This is a report of a 71-year-old woman who presented with several months of a lower abdominal mass and recent onset of associated abdominal discomfort. An earlier colonoscopy 8 months previously was unremarkable. A recent abdominal and pelvic computed tomography scan revealed a necrotic mass in the central mesentery. She underwent surgical resection of the mass to include the overlying segment of the small intestine and had an uneventful convalescence. Mesenteric leiomyosarcoma is a rare tumor that is diagnosed based on histological examination with immunohistochemistry. As a result, there is minimal information on its clinical presentation, pathology, and treatment.
Topics: Aged; Female; Humans; Immunohistochemistry; Intestine, Small; Leiomyosarcoma; Mesentery; Tomography, X-Ray Computed
PubMed: 35420902
DOI: 10.1177/00031348221087921 -
Internal Medicine (Tokyo, Japan) Sep 2020A 44-year-old woman presented to our hospital with abdominal pain. Abdominal ultrasonography and computed tomography showed a mass-like change in the lesser omentum...
A 44-year-old woman presented to our hospital with abdominal pain. Abdominal ultrasonography and computed tomography showed a mass-like change in the lesser omentum between the liver and stomach. Esophagogastroduodenoscopy revealed a submucosal tumor-like change, and endoscopic ultrasonography (EUS) revealed that the mass was located outside of the stomach wall. We performed EUS fine-needle aspiration and diagnosed panniculitis of the lesser omentum. Based on these findings, we suggest that mass-like lesions in the lesser omentum and submucosal tumor-like changes in the anterior wall on the lesser curvature side of the stomach be evaluated for the possibility of panniculitis of the lesser omentum.
Topics: Adult; Biopsy, Fine-Needle; Endosonography; Female; Humans; Omentum; Panniculitis, Peritoneal; Tomography, X-Ray Computed
PubMed: 32461523
DOI: 10.2169/internalmedicine.4300-19 -
International Journal of Obesity (2005) Sep 2019The effects of probiotic Bifidobacterium animalis subsp. lactis CECT 8145 (Ba8145) and those of its heat-killed form (h-k Ba8145) on human anthropometric adiposity... (Randomized Controlled Trial)
Randomized Controlled Trial
Effects of daily consumption of the probiotic Bifidobacterium animalis subsp. lactis CECT 8145 on anthropometric adiposity biomarkers in abdominally obese subjects: a randomized controlled trial.
BACKGROUND
The effects of probiotic Bifidobacterium animalis subsp. lactis CECT 8145 (Ba8145) and those of its heat-killed form (h-k Ba8145) on human anthropometric adiposity biomarkers are unknown.
OBJECTIVE
To assess the effect of Ba8145 and h-k Ba8145 ingestion on anthropometric adiposity biomarkers.
DESIGN
Randomized, parallel, double-blind, placebo-controlled trial with abdominally obese individuals. Participants (n = 135) consumed 1 capsule/day containing 10 colony forming unit (CFU) of Ba8145, 10 CFU of h-k Ba8145, or placebo (maltodextrin) for 3 months.
RESULTS
Ba8145 ingestion decreased waist circumference, waist circumference/height ratio, and Conicity index (P < 0.05) versus its baseline. Changes versus the placebo group reached significance (P < 0.05) after the h-k Ba8145 treatment. Ba8145 decreased the body mass index compared with baseline and placebo group (P < 0.05). The decrease in visceral fat area after Ba8145 treatments reached significance (P < 0.05) only after h-k Ba8145. When analyses by gender were performed, significance remained only for women. Diastolic blood pressure and HOMA index decreased (P < 0.05) after h-k Ba8145. Gut microbiome analyses showed an increase in Akkermansia spp. after Ba8145 treatment, particularly in the live form, which was inversely related to weight (P = 0.003).
CONCLUSIONS
In abdominally obese individuals, consumption of Ba8145, both as viable and mainly as heat-killed cells, improves anthropometric adiposity biomarkers, particularly in women. An increase in the gut Akkermansia genus appears as a possible mechanism involved. Our results support Ba8145 probiotic as a complementary strategy in obesity management.
Topics: Adiposity; Adult; Bifidobacterium animalis; Female; Humans; Male; Obesity, Abdominal; Probiotics; Waist Circumference
PubMed: 30262813
DOI: 10.1038/s41366-018-0220-0 -
Taiwanese Journal of Obstetrics &... Jan 2022Inguinal endometriosis is a very rare entity with uncertain pathophysiology, that poses several diagnostic and therapeutic challenges. This study aimed to summarize... (Review)
Review
Inguinal endometriosis is a very rare entity with uncertain pathophysiology, that poses several diagnostic and therapeutic challenges. This study aimed to summarize published literature on the diagnosis and treatment of this condition. Thus, a systematic literature search was conducted in PubMed/MEDLINE, Scopus and the Cochrane Library. An effort was made to numerically analyze all parameters included in case reports and retrospective analyses, as well. The typical and atypical features of this condition, investigations used, type of treatment and histopathology were recorded. More specifications about the surgical treatment, such as operations previously performed, type of surgery and treatment after surgery have been acknowledged. Other sites of endometriosis, the presence of pelvic endometriosis and the follow-up and recurrence have been also documented. Overall, the search yielded 61 eligible studies including 133 cases of inguinal endometriosis. The typical clinical presentation includes a unilateral inguinal mass, with or without catamenial pain. Transabdominal or transvaginal ultrasound was typically used as the first line method of diagnosis. Groin incision and exploratory surgery was the treatment indicated by the majority of the authors, while excision of part of the round ligament was reported in about half of the cases. Chemotherapy and radiotherapy were initiated in cases of coexisting endometriosis-related neoplasia. Inguinal recurrence or malignant transformation was rarely reported. The treatment of inguinal endometriosis is surgical and a long-term follow-up is needed. More research is needed on the effectiveness of suppressive hormonal therapy, recurrence rate and its relationship with endometriosis-associated malignancies.
Topics: Endometriosis; Female; Groin; Humans; Inguinal Canal; Round Ligament of Uterus; Treatment Outcome; Ultrasonography
PubMed: 35181041
DOI: 10.1016/j.tjog.2021.11.007 -
Annals of the Royal College of Surgeons... Feb 2020Gynaecological structures such as the ovaries, fallopian tubes, ligaments and uterus are rarely encountered inside a hernial sac. The prevalence of groin hernias...
INTRODUCTION
Gynaecological structures such as the ovaries, fallopian tubes, ligaments and uterus are rarely encountered inside a hernial sac. The prevalence of groin hernias containing parts of female genitalia remains unknown. The aim of this review was to summarise the existing evidence on inguinal hernias containing ovaries with or without the other female adnexa.
METHODS
A systematic search was conducted for literature published up to February 2018 using the MEDLINE, Scopus and Google Scholar™ databases along with the references of the full-text articles retrieved. Papers on observational studies and case reports concerning women who were diagnosed with an ovarian inguinal hernia (pre or intraoperatively) were considered eligible for inclusion in the review.
RESULTS
Fifteen papers (13 case reports, 2 case series) comprising seventeen patients (mean age 47.9 years) were evaluated. A left-sided hernia was noted in 13 cases (77%) whereas 4 patients had a right-sided hernia. Eight patients underwent preoperative imaging with computed tomography, ultrasonography or both. This was diagnostic in five cases. In 11 patients, hernia contents were repositioned, 2 had a salpingo-oophorectomy and 2 an oophorectomy. Eight patients underwent hernia repair with mesh placement while three had a herniorrhaphy.
CONCLUSIONS
Ovarian inguinal hernias should be considered among the differential diagnoses of a groin mass or swelling. In women of reproductive age, repair of the hernia with the intent to preserve fertility is of critical importance.
Topics: Female; Hernia, Inguinal; Herniorrhaphy; Humans; Inguinal Canal; Ovarian Diseases; Ovariectomy; Ovary; Prevalence; Salpingo-oophorectomy; Surgical Mesh; Tomography, X-Ray Computed; Ultrasonography
PubMed: 31696731
DOI: 10.1308/rcsann.2019.0137 -
Radiographics : a Review Publication of... 2020Abdominal wall masses, masslike lesions, and diffuse processes are common and often incidental findings at cross-sectional imaging. Distinguishing among these types of... (Review)
Review
Abdominal wall masses, masslike lesions, and diffuse processes are common and often incidental findings at cross-sectional imaging. Distinguishing among these types of masses on the basis of imaging features alone can be challenging. The authors present a diagnostic algorithm that may help in distinguishing different types of abdominal wall masses accurately. Hernias may mimic discrete masses at clinical examination, and imaging is often ordered for evaluation of a possible abdominal wall mass. Once a discrete mass is confirmed to be present, the next step is to determine if it is a fat-containing, cystic, or solid mass. The most common fat-containing masses are lipomas. Fluid or cystic masses include postoperative abscesses, seromas, and rectus sheath hematomas. Solid masses are the most common abdominal wall masses and include desmoid tumors, sarcomas, endometriomas, and metastases. Multiple masses and other diffuse abdominal wall processes are often manifestations of an underlying condition or insult. The most frequently found diffuse processes are multiple injection granulomas from administration of subcutaneous medication. This article offers an algorithmic approach to characterizing abdominal wall masses on the basis of their composition and reviews abdominal wall diffuse processes. RSNA, 2020.
Topics: Abdominal Neoplasms; Abdominal Wall; Cysts; Diagnosis, Differential; Endometriosis; Female; Hematoma; Hernia, Abdominal; Humans; Incidental Findings; Lipoma; Male; Postoperative Complications; Seroma; Soft Tissue Neoplasms
PubMed: 32330085
DOI: 10.1148/rg.2020190170 -
Radiology May 2022Opportunistic CT screening leverages robust imaging data embedded within abdominal and thoracic scans that are generally unrelated to the specific clinical indication... (Review)
Review
Opportunistic CT screening leverages robust imaging data embedded within abdominal and thoracic scans that are generally unrelated to the specific clinical indication and have heretofore gone largely unused. This incidental imaging information may prove beneficial to patients in terms of wellness, prevention, risk profiling, and presymptomatic detection of relevant disease. The growing interest in CT-based opportunistic screening relates to a confluence of factors: the objective and generalizable nature of CT-based body composition measures, the emergence of fully automated explainable AI solutions, the sheer volume of body CT scans performed, and the increasing emphasis on precision medicine and value-added initiatives. With a systematic approach to body composition and other useful CT markers, initial evidence suggests that their ability to help radiologists assess biologic age and predict future adverse cardiometabolic events rivals even the best available clinical reference standards. Emerging data suggest that standalone "intended" CT screening over an unorganized opportunistic approach may be justified, especially when combined with established cancer screening. This review will discuss the current status of opportunistic CT screening, including specific body composition markers and the various disease processes that may be impacted. The remaining hurdles to widespread clinical adoption include generalization to more diverse patient populations, disparate technical settings, and reimbursement.
Topics: Abdomen; Early Detection of Cancer; Humans; Mass Screening; Retrospective Studies; Tomography, X-Ray Computed
PubMed: 35289661
DOI: 10.1148/radiol.211561 -
Revista Espanola de Enfermedades... Jan 2021A giant cystic lymphangioma in the pancreatic body-tail was diagnosed as an incidental ultrasound mass in a 41-year-old patient, with a progressive size that had...
A giant cystic lymphangioma in the pancreatic body-tail was diagnosed as an incidental ultrasound mass in a 41-year-old patient, with a progressive size that had increased in the last year by about 20 cm size. An ultrasound guided fine needle puncture was performed and the result was a benign cystic lesion. Given the increase in size, a surgical intervention was decided. A retroperitoneal cystic tumor dependent on the posterior pancreatic wall was identified and a full laparoscopic resection with pancreas and spleen preservation was performed. The pathological report confirmed the diagnosis of benign cystic lymphangioma. The patient was discharged on the fifth postoperative day without any remarkable complications. After one year of follow-up, the patient remains asymptomatic.
Topics: Adult; Humans; Lymphangioma; Lymphangioma, Cystic; Pancreas; Pancreatic Neoplasms; Retroperitoneal Space
PubMed: 33207886
DOI: 10.17235/reed.2020.7003/2020