An Extreme Case of Lethal Abdominal Compartment Syndrome in Pediatric Patient With Synovial Sarcoma.

There is a relative paucity of literature on abdominal compartment syndrome (ACS) in children compared to adults and even less describing ACS in pediatric oncologic patients. We present this case of ACS in a 14-year-old patient to highlight the acuity of lethal consequences despite swift adequate management. Our patient is a 14-year-old male with a history of non-verbal autism and large synovial sarcoma of the left chest wall. He was admitted for scheduled inpatient chemotherapy and radiation. On day 3 of admission, the patient's clinical condition rapidly deteriorated, and a surgical abdomen was found on the exam. In the operating room (OR), massive gaseous distention of the stomach, small intestines, and colon were noted. A loop of small bowel was under such high pressure that the force of evisceration sheared the bowel from the associated mesentery. Due to the severity of the dilated bowel loops, we could not return the eviscerated bowel back inside the abdomen, which led us to leave the Abthera wound vac as sole coverage. The patient was transferred to the PICU, and medical treatment was aimed toward palliative care. The patient passed away three hours later. This case illustrates the acute and lethal nature of ACS in a less studied population, the pediatric oncologic patient. Prompt detection and treatment of ACS are essential for the management of critically ill pediatric patients, especially in those with space occupying tumors within the abdominal cavity. However, extreme presentations of ACS can have lethal consequences despite swift surgical intervention and adequate management.

Single-Incision Laparoscopic Appendectomy Using Standard 5 mm Trocars: Single Pediatric Center Experience.

Purpose: Single-incision laparoscopic appendectomy (SILA) for the treatment of appendicitis has been documented. Typically, SILA requires the use of specialized ports, instruments, and materials. The SILA technique at our institution utilizes the same instrumentation as the conventional laparoscopic approach (CLA), thus obviating the need for these specialized products. This study aims to further demonstrate the noninferiority of our SILA technique for the treatment of uncomplicated appendicitis. Materials and Methods: This is a single-institution retrospective review of patients who underwent SILA from 2011 to 2020 to treat uncomplicated appendicitis. Outcomes including demographics, operative time, length of stay (LOS), and common postsurgical complications were evaluated. These SILA cases were matched with up to 3 CLA controls based on age, gender, and weight utilizing the Greedy match method. Patients with an operative diagnosis of perforated appendicitis were excluded. Results: A total of 137 patients underwent SILA at a single institution. A total of 128 patients were in the final cohort after excluding perforated appendicitis. Mean age was 11.9 years. Case-control matching was conducted with 349 controls included. Between cases and controls, SILA had shorter operative time (27.2 minutes versus 43.7 minutes, P < .001) with no difference in mean LOS (42.4 hours versus 42.4 hours, P = .88). There was no difference in complication rate (5.4% versus 8.5%, P = .06). There was no difference in readmission rate (0.8% versus 3.4%, P = .108). Conclusion: These data suggest that for appropriately selected patients, our SILA technique is noninferior to CLA with shortened operative time.

Congenital Giant Megaureter in a 16-Year-Old Female Presenting With Abdominal Pain: A Case Report and Review of Literature.

We describe a case of congenital giant megaureter in a 16-year-old female. She presented with a 5-day history of abdominal distention, right flank pain and tenderness. Right pyelonephritis was suspected. Computerized tomography showed a large cystic abdominal mass with no appreciably functioning left kidney causing secondary compression of the contralateral right ureter. A left upper nephroureterectomy was performed, draining over 3.5 L of fluid. Our experience suggests that congenital giant megaureter should be considered in the differential for pediatric patients presenting with a cystic abdominal mass.

A Rare Case of Henoch-Schönlein Purpura and Mycobacterium xenopi Pulmonary Infection.

Henoch-Schönlein purpura (HSP) is a small-vessel vasculitis with cutaneous, articular, gastrointestinal, and renal manifestations. Leukocytoclastic vasculitis and IgA deposits are classically found when involved skin and kidneys are biopsied. The disease's etiology remains unknown, although many bacterial and viral infections have been described as triggering factors. A 53-year-old woman presented with fever, arthralgia, and non-thrombocytopenic purpura. She also had a segmental pulmonary collection with peripheral alveolar consolidation. Staphylococcus aureus and mycobacteria growth was found on sputum cultures. In addition to intravenous antibiotics and anti-mycotic drugs, high-dose corticosteroids were urgently administered due to the development of severe intestinal symptoms. A cutaneous biopsy later confirmed HSP. Microbial identification yielded Mycobacterium xenopi. In the review of the literature, we only found 12 cases of Mycobacterium tuberculosis and one case of Mycobacterium avium-intracellulare complex that were associated with HSP. Nearly, half of the cases responded to anti-mycotic treatment alone. The rest required immunosuppressants.  We report the first case of M. xenopi pulmonary infection in HSP. This disease process can have a severe course, which requires rapid recognition and treatment.

A loop involving NRF2, miR-29b-1-5p and AKT, regulates cell fate of MDA-MB-231 triple-negative breast cancer cells.

The present study shows that nuclear factor erythroid 2-related factor 2 (NRF2) and miR-29b-1-5p are two opposite forces which could regulate the fate of MDA-MB-231 cells, the most studied triple-negative breast cancer (TNBC) cell line. We show that NRF2 activation stimulates cell growth and markedly reduces reactive oxygen species (ROS) generation, whereas miR-29b-1-5p overexpression increases ROS generation and reduces cell proliferation. Moreover, NRF2 downregulates miR-29b-1-5p expression, whereas miR-29b-1-5p overexpression decreases p-AKT and p-NRF2. Furthermore, miR-29b-1-5p overexpression induces both inhibition of DNA N-methyltransferases (DNMT1, DNMT3A, and DNMT3B) expression and re-expression of HIN1, RASSF1A and CCND2. Conversely, NRF2 activation induces opposite effects. We also show that parthenolide, a naturally occurring small molecule, induces the expression of miR-29b-1-5p which could suppress NRF2 activation via AKT inhibition. Overall, this study uncovers a novel NRF2/miR-29b-1-5p/AKT regulatory loop that can regulate the fate (life/death) of MDA-MB-231 cells and suggests this loop as therapeutic target for TNBC.

Unexpected Gastric Ectopic Pancreas During Sleeve Gastrectomy: A Case Report.

BACKGROUND Ectopic or heterotopic pancreas is relatively rare pathology described as pancreatic tissue lacking communication with the normal pancreas. Ectopic pancreatic tissue can be found along the gastrointestinal tract, with the most common location the stomach along the greater curvature. This congenital condition could be identified incidentally, or present with symptoms that range from pain and bleeding to obstruction and malignant transformation. CASE REPORT We report a case of a 30-year-old female, who underwent laparoscopic sleeve gastrectomy for morbid obesity of body mass index (BMI) of 46 kg/m², and who was found to have a 3 cm submucosal mass at the lesser curvature while dividing the stomach. The sleeved stomach tube's intraoperative gastroscopy showed a submucosal mass at the posterior stomach wall towards the lesser curvature, increasing the suspicion of gastrointestinal stromal tumor (GIST) tumor. The choice was to continue with a secure margin and conversion to roux-en-y gastric bypass with gastric tumor resection. It turned out that the final pathology was submucosal ectopic pancreas. Despite being a rare pathology, for any submucosal gastric mass, ectopic pancreas should be on the differential diagnosis list. During the sleeve surgery, the mass was found, and the approach was changed to intraoperatively subtotal gastrectomy and roux-en-y gastric bypass. CONCLUSIONS Before any bariatric operation, even in asymptomatic young patients, it is worth doing routine upper endoscopy to prevent surprising intraoperative pathology.

Chest Wall Reconstruction with a Bilayered Wound Matrix Mesh Following Toilet Mastectomy.

BACKGROUND Breast cancer is still the most common malignancy in women. Though management of local disease has been thoroughly studied, management of metastatic breast cancer (MBC) is still under much debate. Modern diagnostic tools allow the detection of early metastatic disease, which may be more responsive to treatment than late metastatic disease. Source control of MBC by "toilet mastectomy" is being studied in many case reports and studies. CASE REPORT We present the case of a 43-year-old woman presenting with MBC and complaining of a recurrent breast fungating disease, aiming to highlight the importance of palliative surgical treatment in systemic breast malignancy and to report our experience with the effectiveness of the 'Integra" mesh. CONCLUSIONS Chest wall reconstruction using bilayered wound matrix mesh following "toilet mastectomy" offers excellent reconstructive results and local control of disease, and is a low-morbidity procedure.

Idiopathic Ileo-Ileo-Cecal Intussuception in a 25-Year-Old Female.

BACKGROUND Intussusception is defined as the penetration or telescoping of a segment of bowel into a more distal segment. Intussusception is a common cause of small bowel obstruction, especially in children. However, this finding is much less common in adults. Furthermore, when present in adults, intussusception is often found in association with some sort of organic mass, such as a tumor or pancreatic divisum that acts as a lead point, dragging the proximal segment into the distal one. The presence of an intussusception in an adult patient with no obvious lead point is very uncommon. CASE REPORT Here we report a case of ileo-ileo-cecal double intussusception in an adult patient that yielded no lead point on surgical exploration. The patient was a 25-year-old female who presented with symptoms of obstruction and was diagnosed with the intussusception via computed tomography scan. Surgical resection of the bowel was necessary as reduction could not be accomplished. CONCLUSIONS The finding of intussusception in an adult patient is far less common than in children, and even more rare when a lead point is not established. When surgery is required, a thorough exploration should be performed to search any signs of a potential lead point. Laparoscopy is usually preferred to laparotomy; however, in this case the degree of distention determined the surgical approach. Thus, due to severe distention, laparotomy was preferred.

Aspirin impairs acetyl-coenzyme A metabolism in redox-compromised yeast cells.

Aspirin is a widely used anti-inflammatory and antithrombotic drug also known in recent years for its promising chemopreventive antineoplastic properties, thought to be mediated in part by its ability to induce apoptotic cell death. However, the full range of mechanisms underlying aspirin's cancer-preventive properties is still elusive. In this study, we observed that aspirin impaired both the synthesis and transport of acetyl-coenzyme A (acetyl-CoA) into the mitochondria of manganese superoxide dismutase (MnSOD)-deficient Saccharomyces cerevisiae EG110 yeast cells, but not of the wild-type cells, grown aerobically in ethanol medium. This occurred at both the gene level, as indicated by microarray and qRT-PCR analyses, and at the protein level as indicated by enzyme assays. These results show that in redox-compromised MnSOD-deficient yeast cells, but not in wild-type cells, aspirin starves the mitochondria of acetyl-CoA and likely causes energy failure linked to mitochondrial damage, resulting in cell death. Since acetyl-CoA is one of the least-studied targets of aspirin in terms of the latter's propensity to prevent cancer, this work may provide further mechanistic insight into aspirin's chemopreventive behavior with respect to early stage cancer cells, which tend to have downregulated MnSOD and are also redox-compromised.

Abdominal Wall Endometriosis: A Case Report.

Abdominal wall endometriosis is a rare condition that occurs after a cesarean section or pelvic surgery and it has an incidence of 0.03%-1.5% in women with previous cesarean delivery. The predominant clinical picture is cyclic pain. We report two cases of abdominal wall endometriosis. The first was a 36-year-old female patient who presented for recurrent cyclic abdominal pain and was found to have endometriosis near the cesarean scar. The second was a 40-year-old female who had the same clinical presentation and was found to have endometriosis away from the scar. These cases highlight the need to have a high index of suspicion when treating women with recurrent cyclic abdominal pain.

Loss of MCL1 function sensitizes the MDA-MB-231 breast cancer cells to rh-TRAIL by increasing DR4 levels.

Triple-negative breast cancer (TNBC) is a form of BC characterized by high aggressiveness and therapy resistance probably determined by cancer stem cells. MCL1 is an antiapoptotic Bcl-2 family member that could limit the efficacy of anticancer agents as recombinant human tumor necrosis factor related apoptosis-inducing ligand (rh-TRAIL). Here, we investigated MCL1 expression in TNBC tissues and cells. We found MCL1 differentially expressed (upregulated or downregulated) in TNBC tissues. Furthermore, in comparison to the human mammary epithelial cells, we found that MDA-MB-231 cells show similar messenger RNA levels but higher MCL1 protein levels, whereas it resulted downregulated in MDA-MB-436 and BT-20 cells. We evaluated the effects of rh-TRAIL and A-1210477, a selective MCL1 inhibitor, on cell viability and growth of MDA-MB-231 cells. We demonstrated that the drug combination reduced the cell growth and activated the apoptotic pathway. Similar effects were observed on three-dimensional cultures and tertiary mammospheres of MDA-MB-231 cells. In MDA-MB-231 cells, after MCL1 silencing, rh-TRAIL confined the cell population in the sub-G0/G1 phase and induced a drop in the mitochondrial transmembrane potential. To understand the molecular mechanism by which the loss of MCL1 function sensitizes the MDA-MB-231 cells to rh-TRAIL, we analyzed by real-time reverse transcription polymerase chain reaction, the expression of genes related to apoptosis, stemness, cell cycle, and those involved in epigenetic regulation. Interestingly, among the upregulated genes through MCL1 silencing or inhibition, there was TNFRSF10A (DR4). Moreover, MCL1 inhibition increased DR4 protein levels and its cell surface expression. Finally, we demonstrated MCL1-DR4 interaction and dissociation of this complex after A-1210477 treatment. Overall, our findings highlight the potential MCL1-roles in MDA-MB-231 cells and suggest that MCL1 targeting could be an effective strategy to overcome TNBC's rh-TRAIL resistance.

Pitfalls of Diagnosing Left Lower Quadrant Pain Causes: Making the Uncommon Common Again.

BACKGROUND Left-sided acute appendicitis, although well described in the literature, is still an easily missed diagnosis. Midgut malrotation and situs inversus are 2 known leading conditions that contribute to misdiagnosis of appendicitis. CASE REPORT Here is the case of a 27-year-old male without any previous medical history, who presented with left lower quadrant tenderness and was misdiagnosed with gastroenteritis as an outpatient and sent home; the patient presented the next day to the emergency department where he was found to have acute appendicitis with situs inversus. He underwent laparoscopic appendectomy where a phlegmon was identified. Pathology came back as peri-appendiceal mucocele with no signs of malignancy. CONCLUSIONS This case report aimed to revisit the idea of left-sided acute appendicitis and discuss the management of a perforated appendiceal mucocele contained by a phlegmon.

Gastrobronchial Fistula Following a Laparoscopic Sleeve Gastrectomy.

BACKGROUND Bariatric operations have been gaining more ground over the past decade. The most commonly used bariatric operation is the laparoscopic sleeve gastrectomy. A complication of laparoscopic sleeve gastrectomy is gastric leak; which can rarely cause a primary subphrenic abscess and a secondary diaphragm rupture that will lead eventually to a gastrobronchial fistula. CASE REPORT We present the case of a 32-year-old patient who started having symptoms suggestive of gastrobronchial fistula at 2 months following laparoscopic sleeve gastrectomy. CONCLUSIONS The treatment of a gastrobronchial fistula is controversial as this complication is rarely covered in published studies. Our expert opinion for this patient case was to opt for a surgical approach seeing that the complexity and severity of the fistula had a low chance of subsiding after only conservative measures.

Bead-based RNA multiplex panels for biomarker detection in oncology samples.

Patient stratification, prognosis and disease monitoring are three important aspects of personalized cancer medicine. With traditional serum tumour protein biomarkers showing lack of specificity and sensitivity, and tumour heterogeneity affecting the response to targeted therapy based on tissue biomarkers, the focus has shifted to the use of molecular tumour signatures as specific biomarkers. Multiplex microsphere-based panels are robust and cost-effective, high throughput molecular assays, which can accurately characterize tumours even from small amounts of poor quality nucleic acids. Only few studies have reported the use of microspheres (beads) to quantify RNA expression of targets of interest simultaneously (multiplexing). This review is an overview of the various applications of bead-based RNA panels in molecular oncology, with focus on the Invitrogen™ QuantiGene™ Plex Assay (Thermo Fisher Scientific), and provides a comparison with PCR-based and other methodologies. The advantages of multiplex bead assays are exemplified by the quantification of RNA expression in formalin-fixed, paraffin embedded (FFPE) archival tissue and the simultaneous detection of biomarkers in low input samples, including quantification of markers in microdissected tissue material, to characterise heterogeneous tumour sites within a sample, and by the detection of markers in low numbers of circulating tumour cells.

An Unusual Case of Intestinal Malrotation Causing Duodenal Obstruction by a Looped Appendix.

BACKGROUND Bowel obstruction is a mechanical or functional obstruction of the intestines which prevents the normal movement of the products of digestion. Intestinal malrotation is one of the rarest causes of mechanical bowel obstruction. In adults, the incidence rate is 0.2%, and 15% of all patients with confirmed diagnosis remain asymptomatic throughout life. Surgery is generally required when the patient is symptomatic. CASE REPORT A 30-year-old man with multiple admissions for chronic intermittent colicky abdominal pain since childhood, was admitted for symptoms suggestive of proximal small bowel obstruction. Tomographic imaging identified a midgut malrotation and a duodenal obstruction by a non-diseased displaced appendix. Laparoscopic liberation of the duodenum and the terminal ilium was done successfully. CONCLUSIONS Intestinal malrotation is infrequently encountered in the adult population, but it should be kept in mind as a differential diagnosis whenever a case of acute intestinal obstruction in an adult presents without any significant past surgical history.

Periampullary Neuroendocrine Tumor as a Cause of Acute Pancreatitis.

BACKGROUND Duodenal and ampullary carcinoids are very rare tumors accounting respectively for 2% and 0.03% of all carcinoid tumors. Clinical findings vary according to the location of the tumor within the periampullary region; with epigastric pain being the most common presenting symptom in duodenal carcinoids and jaundice the most common clinical finding in ampullary carcinoids. Treatment options include pancreaticoduodenectomy, local excision, and endoscopic excision. CASE REPORT In this case report, we present a 60-year-old male who presented with a one-week history of intractable epigastric pain. He was diagnosed with duodenal periampullary carcinoid tumor and treated with local excision. CONCLUSIONS Although duodenal and ampullary carcinoid tumors may have different clinical presentations, as well as histochemistry characteristics and metastatic potential, they appear to benefit from the same surgical treatment.

High Frequency of ß-Catenin Mutations in Mouse Hepatocellular Carcinomas Induced by a Nongenotoxic Constitutive Androstane Receptor Agonist.

Activation of Wnt/ß-catenin signaling is frequent in human and rodent hepatocarcinogenesis. Although in mice the tumor-promoting activity of agonists of constitutive androstane receptor (CAR) occurs by selection of carcinogen-initiated cells harboring ß-catenin mutations, the molecular alterations leading to hepatocellular carcinoma (HCC) development by the CAR agonist 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCP) in the absence of genotoxic injury are unknown. Here, we show that CAR activation per se induced HCC in mice and that 91% of them carried ß-catenin point mutations or large in-frame deletions/exon skipping targeting Ctnnb1 exon 3. Point mutations in HCCs induced by TCP alone displayed different nucleotide substitutions compared with those found in HCCs from mice pretreated with diethylnitrosamine. Moreover, unlike those occurring in HCCs from diethylnitrosamine + TCP mice, they did not result in increased expression of ß-catenin target genes, such as Glul, Lgr5, Rgn, Lect2, Tbx3, Axin2, and Ccnd1, or nuclear translocation of ß-catenin compared with the control liver. Remarkably, in the nontumoral liver tissue, chronic CAR activation led to down-regulation of these genes and to a partial loss of glutamine synthetase-positive hepatocytes. These results show that, although chronic CAR activation per se induces HCCs carrying ß-catenin mutations, it concurrently down-regulates the Wnt/ß-catenin pathway in nontumoral liver. They also indicate that the relationship between CAR and ß-catenin may be profoundly different between normal and neoplastic hepatocytes.

Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material.

Nucleic acid degradation in archival tissue, tumor heterogeneity, and a lack of fresh frozen tissue specimens can negatively impact cancer diagnostic services in pathology laboratories worldwide. Gene amplification and expression diagnostic testing using archival material or material that requires transportation to servicing laboratories, needs a more robust and accurate test adapted to current clinical workflows. Our research team optimized the use of Invitrogen™ QuantiGene™ Plex Assay (Thermo Fisher Scientific) to quantify RNA in archival material using branched-DNA (bDNA) technology on Luminex xMAP® magnetic beads. The gene expression assay described in this manuscript is a novel, quick, and multiplex method that can accurately classify breast cancer into the different molecular subtypes, omitting the subjectivity of interpretation inherent in imaging techniques. In addition, due to the low input of material required, heterogeneous tumors can be laser microdissected using Hematoxylin and Eosin (H&E) stained sections. This method has a wide range of possible applications including tumor classification with diagnostic potential and measurement of biomarkers in liquid biopsies, which would allow better patient management and disease monitoring. In addition, the quantitative measurement of biomarkers in archival material is useful in oncology research with access to libraries of clinically-annotated material, in which retrospective studies can validate potential biomarkers and their clinical outcome correlation.

Leishmania in a Patient with Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia.

BACKGROUND Leishmaniasis is a parasitic infection spread by the bite of infected sand flies that are usually present in the Middle East, Africa, and some parts of Asia and Europe. Leishmaniasis manifests in 3 different forms: Visceral (also known as Kala Azar), which is the most serious type; cutaneous, which is the most common type; and mucocutaneous. The symptoms of this infection range from a silent infection to fever, enlargement of the liver and spleen, weight loss, and pancytopenia. CASE REPORT In this case report, we discuss a 73-year-old man known to have chronic lymphocytic leukemia (CLL), presenting with unremitting fever and who to our surprise was found to have Kala Azar. CONCLUSIONS Early diagnosis and treatment are very important in treating visceral leishmaniasis. While the conventional treatment in immunocompromised patients is liposomal amphotericin B, our patient responded to corticosteroids.

CIP2A expression predicts recurrences of tamoxifen-treated breast cancer.

CIP2A is emerging as an oncoprotein overexpressed commonly across many tumours and generally correlated with higher tumour grade and therapeutic resistance. CIP2A drives an oncogenic potential through inhibiting protein phosphatase 2A, stabilizing MYC, and promoting epithelial-to-mesenchymal transition, although further biological mechanisms for CIP2A are yet to be defined. CIP2A protein expression was studied by immunohistochemistry in oestrogen receptor-positive primary breast cancers (n = 250) obtained from the Leeds Tissue Bank. In total, 51 cases presented with a relapse or metastasis during adjuvant treatment with tamoxifen and were regarded as tamoxifen resistant. CIP2A expression was scored separately for cytoplasmic, nuclear, or membranous staining, and scores were tested for statistically significant relationships with clinicopathological features. Membranous CIP2A was preferentially expressed in cases who experienced a recurrence during tamoxifen treatment thus predicting a worse overall survival (log rank = 8.357, p = 0.004) and disease-free survival (log rank = 21.766, p < 0.001). Cox multivariate analysis indicates that it is an independent prognostic indicator for overall survival (hazard ratio = 4.310, p = 0.013) and disease-free survival (hazard ratio = 5.449, p = 0.002). In this study, we propose the assessment of membranous CIP2A expression as a potential novel prognostic and predictive indicator for tamoxifen resistance and recurrence within oestrogen receptor-positive breast cancer.