Giant Extraluminal Leiomyoma of the Colon: Rare Cause of Symptomatic Pelvic Mass

Leiomyomas (LMs) may appear throughout the entire gastrointestinal tract but are rarely seen in the colon-rectum and only 5 of those measured greater than 15 cm in diameter. Pain and palpable abdominal mass are the most common symptoms. Surgical resection is the treatment of choice for most LMs. We here describe a case of a 46-year-old woman who presented with a 3-month history of abdominal pain associated with worsening constipation and abdominal distension. A pelvic solid, polylobulate, left-sided mass was noted on examination. Preoperative findings revealed a dishomogeneous sigmoid mass with calcified spots compressing small intestine and bladder. At laparotomy, a large polylobulate and well-circumscribed mass arising from the descending colon mesentery and displacing small intestine, uterus, and ovaries. A segmental colon resection was performed. An extraluminal 18- × 12- × 5-cm paucicellular sigmoid colon leiomyoma was histologically diagnosed. Our case is one of the few giant (>15 cm) sigmoid colon LMs reported in the literature. Although rare and benign in nature, LMs of the colon can cause life-threatening complications that could require emergency treatment and they should be included in the differential diagnosis of large abdominopelvic masses. Follow-up after surgery is necessary for tumors with any atypia or mitotic activity.Key words: Leiomyoma, Digestive tract, Bowel obstruction, Pelvic massPrimary leiomyomas (LMs) present most commonly in the female genital tract and skin but they are rarely seen in the colon-rectum. Macroscopically, LMs may be intraluminal, intramural, extramural, or dumbbell.^1,2 The majority of LMs remain asymptomatic until they have reached a large size: most common symptoms are pain and palpable abdominal mass.^1,2 Symptomatic left colon LMs are uncommon and only 5 of those reported in the literature measured greater than 15 cm in diameter.¹ Histologically, most of them arise from the muscularis propria.^1,3 The most important differential diagnoses are malignant leiomyosarcoma and gastrointestinal stromal tumors (GIST).^1,3 Surgical resection is the treatment of choice for large LMs: complete excision should be always attempted and follow up is necessary for tumors with any atypia or mitotic activity.^1,2 Although rare and benign in nature, LMs of the colon can cause life-threatening complications that require emergency treatment.^1–3 We here describe a case of large extraluminal sigmoid colon LM causing pain and worsening bowel obstruction.     

Are Nephroenteric Fistulas Only a Surgical Trouble?

Nephroenteric fistulas can be secondary to different etiologies, the most common of which are pyelocolic fistulas. The absence of pathognomonic symptoms and the heterogeneity of presentation can sometimes result in a delay in diagnosis. We report on three cases: a pyelo-duodenal fistula secondary to kidney stones and subsequent pyonephrosis, a pyelocolic fistula due to inveterate ureteral stones with hydropyonephrosis, and a rare case of posttraumatic pyelocolic fistula. All patients were treated with radical nephrectomy and resection of the involved intestinal tract. Fistulas of the kidney with the gastrointestinal tract are complex not only for the surgical treatment, which is mandatory in the majority of cases, but also for clinical and instrumental diagnosis. Severe infection is a major concern due to the admixture of the enteric bacterial flora with the urinary tract. Nephroenteric fistulas require skilled surgical procedures, close control of the septic risk, management of patient''s overall medical condition, and balance between invasive and conservative approach.     

AKI Recovery Induced by Mesenchymal Stromal Cell-Derived Extracellular Vesicles Carrying MicroRNAs

Phenotypic changes induced by extracellular vesicles have been implicated in mesenchymal stromal cell–promoted recovery of AKI. MicroRNAs are potential candidates for cell reprogramming toward a proregenerative phenotype. The aim of this study was to evaluate whether microRNA deregulation inhibits the regenerative potential of mesenchymal stromal cells and derived extracellular vesicles in a model of glycerol-induced AKI in severe combined immunodeficient mice. We generated mesenchymal stromal cells depleted of Drosha to alter microRNA expression. Drosha-knockdown cells produced extracellular vesicles that did not differ from those of wild-type cells in quantity, surface molecule expression, and internalization within renal tubular epithelial cells. However, these vesicles showed global downregulation of microRNAs. Whereas wild-type mesenchymal stromal cells and derived vesicles administered intravenously induced morphologic and functional recovery in AKI, the Drosha-knockdown counterparts were ineffective. RNA sequencing analysis showed that kidney genes deregulated after injury were restored by treatment with mesenchymal stromal cells and derived vesicles but not with Drosha-knockdown cells and vesicles. Gene ontology analysis showed in AKI an association of downregulated genes with fatty acid metabolism and upregulated genes with inflammation, matrix-receptor interaction, and cell adhesion molecules. These alterations reverted after treatment with wild-type mesenchymal stromal cells and extracellular vesicles but not after treatment with the Drosha-knockdown counterparts. In conclusion, microRNA depletion in mesenchymal stromal cells and extracellular vesicles significantly reduced their intrinsic regenerative potential in AKI, suggesting a critical role of microRNAs in recovery after AKI.     

Mechanisms of altered bone remodeling in children with type 1 diabetes

Bone loss associated with type 1 diabetes mellitus (T1DM) begins at the onset of the disease, already in childhood, determining a lower bone mass peak and hence a greater risk of osteoporosis and fractures later in life. The mechanisms underlying diabetic bone fragility are not yet completely understood. Hyperglycemia and insulin deficiency can affect the bone cells functions, as well as the bone marrow fat, thus impairing the bone strength, geometry, and microarchitecture. Several factors, like insulin and growth hormone/insulin-like growth factor 1, can control bone marrow mesenchymal stem cell commitment, and the receptor activator of nuclear factor-κB ligand/osteoprotegerin and Wnt-b catenin pathways can impair bone turnover. Some myokines may have a key role in regulating metabolic control and improving bone mass in T1DM subjects. The aim of this review is to provide an overview of the current knowledge of the mechanisms underlying altered bone remodeling in children affected by T1DM.     

The Use of Oral Amino-Bisphosphonates and Coronavirus Disease 2019 (COVID-19) Outcomes

The determinants of the susceptibility to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection and severe coronavirus disease 2019 (COVID-19) manifestations are yet not fully understood. Amino-bisphosphonates (N-BPs) have anti-inflammatory properties and have been shown to reduce the incidence of lower respiratory infections, cardiovascular events, and cancer. We conducted a population-based retrospective observational cohort study with the primary objective of determining if oral N-BPs treatment can play a role in the susceptibility to development of severe COVID-19. Administrative International Classification of Diseases, Ninth Revision, Clinical ModificationI (ICD-9-CM) and anatomical-therapeutic chemical (ATC) code data, representative of Italian population (9% sample of the overall population), were analyzed. Oral N-BPs (mainly alendronate and risedronate) were included in the analysis, zoledronic acid was excluded because of the low number of patients at risk. Incidence of COVID-19 hospitalization was 12.32 (95% confidence interval [CI], 9.61–15.04) and 11.55 (95% CI, 8.91–14.20), of intensive care unit (ICU) utilization because of COVID-19 was 1.25 (95% CI, 0.38–2.11) and 1.42 (95% CI, 0.49–2.36), and of all-cause death was 4.06 (95% CI, 2.50–5.61) and 3.96 (95% CI, 2.41–5.51) for oral N-BPs users and nonusers, respectively. Sensitivity analyses that excluded patients with prevalent vertebral or hip fragility fractures and without concomitant glucocorticoid treatment yielded similar results. In conclusion, we found that the incidence of COVID-19 hospitalization, intensive care unit (ICU) utilization, and COVID-19 potentially related mortality were similar in N-BPs–treated and nontreated subjects. Similar results were found in N-BPs versus other anti-osteoporotic drugs. We provide real-life data on the safety of oral N-BPs in terms of severe COVID-19 risk on a population-based cohort. Our results do not support the hypothesis that oral N-BPs can prevent COVID-19 infection and/or severe COVID-19; however, they do not seem to increase the risk. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

B-cell concentration in the apheretic product predicts acute graft-versus-host disease and treatment-related mortality of allogeneic peripheral blood stem cell transplantation

BACKGROUND: The influence of the graft composition on the clinical outcome after allogeneic peripheral blood stem cell (PBSC) transplantation is not well established. METHODS: The cellular composition of the apheretic products obtained from 63 human leukocyte antigen-identical siblings was prospectively correlated with the outcome of patients with hematological malignancies undergoing an allogeneic PBSC transplant after myeloablative conditioning. The concentration of nuclear, mononuclear, CD34+, T-cell subsets, B cells, and natural killer cells in the graft has been analyzed. RESULTS: In univariate analysis, acute graft-versus-host disease (GVHD) correlated with the disease (P=0.002), with the phase of disease at transplant (P=0.01), and with the number of CD20+ cells infused (P=0.05). In multivariate analysis, a dose of CD20+ cells in the graft higher than the median dose remained the only factor negatively affecting the incidence of acute GVHD (P=0.01; 95% confidence interval [CI]: 0.12-0.78). In univariate analysis, treatment-related mortality (TRM) correlated with the disease (P=0.04) and was negatively affected by a dose of infused B cells greater than the median value (28% versus 50%; P=0.02). In multivariate analysis, TRM was close to statistical correlation with the dose of CD20+ cells (P=0.06; 95% CI: 0.02-1.05). No other clinical parameter was influenced by the composition of the graft. CONCLUSIONS: Our results suggest that the concentration of B cells in the apheretic product may predict the incidence of acute GVHD and TRM in patients undergoing an allogeneic PBSC transplantation and open the way to the new preventive and therapeutic strategies for the management of GVHD.     

Increased prevalence of peripheral arterial disease in osteoporotic postmenopausal women

The aim of this study was to investigate the prevalence and correlates of peripheral arterial disease (PAD) in a population of osteoporotic postmenopausal women. The presence of PAD was assessed by ankle brachial index (ABI) in 345 ambulatory osteoporotic postmenopausal women, and in 360 community-based, age- and race-matched postmenopausal women with normal bone mineral density (BMD) (control group). PAD was detected in 63/345 (18.2%) osteoporotic women and in 14/360 (3.8%) control subjects (P < 0.0001). The mean ABI values were significantly lower in the osteoporosis group than in the control group (0.98 ± 0.09 vs. 1.04 ± 0.06, P < 0.0001). No difference in cardiovascular risk factors was observed between osteoporotic patients and controls, or between osteoporotic patients with and without PAD. Osteoporotic patients with PAD had lower femoral neck BMD T scores than those without PAD (−4.2 ± 0.7 vs. −2.3 ± 0.7, P < 0.0001). Only 4 PAD patients (5.1%) had intermittent claudication. In multivariate logistic regression analysis, factors independently associated with PAD within osteoporotic patients were lower femoral neck BMD T score (odds ratio (OR) = 0.20, 95% confidence interval (CI), 0.05–0.70, P = 0.01) and systolic blood pressure (OR = 1.02, 95% CI, 1.00–1.03, P = 0.01). This study shows for the first time an increased prevalence of PAD among osteoporotic postmenopausal women, with a lower femoral neck BMD T score being a significant independent predictor. The findings suggest that vascular status evaluation should be done in osteoporotic postmenopausal women in order to identify candidate patients for preventive and therapeutic cardiovascular interventions.     

Ultrastructural localization of binding sites of sera from patients with linear IgA bullous dermatosis

The localization of the antigen recognized by IgA basement membrane zone (BMZ) antibodies from patients with linear IgA bullous dermatosis (LABD) has not been established. The aim of our study was to find out the binding sites for IgA-BMZ antibodies in LABD in adults and children and, for comparison, the binding sites for IgA antibodies in IgA cicatricial pemphigoid (IgA-CP). Our series comprised 21 sera from adult LABD, 4 sera from childhood LABD, and 2 sera from IgA-CP. The studies were performed using the sodium chloride split-skin method and indirect immunoelectron microscopy (IEM) with the use of the pre-embedding immunoperoxidase techinique on two substrates: monkey oesophagus and normal human skin. Of the 27 sera, 24 reacted with the epidermis (19 from adult, 4 from childhood LABD and 1 from IgA-CP) and at the electron microscopic level labelled the upper part of the lamina lucida (LL) and/or hemidesmosomes, and 2 reacted with the dermis (1 from typical adult LABD and 1 from IgA-CP) and labelled the sublamina densa (SLD) region. Two sera were negative in IEM. In conclusion, the study indicated that the localization of the antigens is similar in adult and childhood LABD, and in IgA-CP.Part of this work was presented during the Second Tricontinental Meeting of the Japanese Society for Investigative Dermatology, the Society for Investigative Dermatology and the European Society for Dermatological Research. October 1993, Kyoto, Japan