Fibrolamellar Hepatocellular Carcinoma (FLHCC) in a Young Patient Presenting With Nausea and Vomiting After a Greasy Meal.

Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare and distinct subtype of liver cancer, predominantly affecting younger patients without underlying liver diseases. This case report discusses a unique presentation of FLHCC in a 38-year-old male with a past medical history of a well-controlled seizure disorder. The patient presented with nausea, vomiting, and abdominal pain following a fatty meal. Laboratory tests revealed elevated liver enzymes and anemia, and imaging showed a large hepatic lesion. Initial management included a septic workup and broad-spectrum antibiotics. However, a liver biopsy performed subsequently revealed the presence of FLHCC. The patient underwent a successful open right hepatectomy and was managed postoperatively with consideration of his seizure disorder. Follow-up at six months showed a stable postoperative condition without any evidence of recurrence. The diagnosis of FLHCC is challenging due to its rarity and nonspecific presentation. The case emphasizes the importance of considering FLHCC in the differential diagnosis of hepatic lesions, particularly in young patients. Surgical resection remains the primary treatment modality. This case underscores the importance of a thorough evaluation of hepatic lesions, especially in younger patients. It also illustrates the complexities in managing patients with FLHCC, requiring a multidisciplinary approach for optimal outcomes. Further research is necessary to better understand the pathogenesis of FLHCC and to develop more effective treatment strategies.

Laparoscopic removal of a dermoid cyst in one ovary and an endometrioma in the other: A case report and literature review.

The coexistence of an endometrioma and a dermoid cyst is very uncommon, and there are few case reports of both conditions in the ovaries. A 41-year-old patient presented with left pelvic pain. She was referred with a bilateral pelvic mass. Magnetic resonance imaging (MRI) confirmed a dermoid cyst on the left ovary and an endometrioma on the right side. The patient was taking ibuprofen to relieve pain until the day of surgery. She was advised to proceed with bilateral laparoscopic cystectomy. During the laparoscopic procedure, the inspection showed that ovaries were bilaterally enlarged with cystic appearances. Bilateral ovarian cystectomy was performed in which a left dermoid cyst was removed intact within the ovary followed by a rupture of the endometrioma on the right. The patient tolerated the procedure without any complications. This case of coexistence of endometrioma and dermoid cyst in each ovary, confirmed by MRI due to atypical findings on ultrasound, highlights how efficient removal of both cyst is crucial.

The Potential of Physical Exercise to Mitigate Radiation Damage-A Systematic Review.

There is a need to investigate new countermeasures against the detrimental effects of ionizing radiation as deep space exploration missions are on the horizon. Objective: In this systematic review, the effects of physical exercise upon ionizing radiation-induced damage were evaluated. Methods: Systematic searches were performed in Medline, Embase, Cochrane library, and the databases from space agencies. Of 2,798 publications that were screened, 22 studies contained relevant data that were further extracted and analyzed. Risk of bias of included studies was assessed. Due to the high level of heterogeneity, meta-analysis was not performed. Five outcome groups were assessed by calculating Hedges' g effect sizes and visualized using effect size plots. Results: Exercise decreased radiation-induced DNA damage, oxidative stress, and inflammation, while increasing antioxidant activity. Although the results were highly heterogeneous, there was evidence for a beneficial effect of exercise in cellular, clinical, and functional outcomes. Conclusions: Out of 72 outcomes, 68 showed a beneficial effect of physical training when exposed to ionizing radiation. As the first study to investigate a potential protective mechanism of physical exercise against radiation effects in a systematic review, the current findings may help inform medical capabilities of human spaceflight and may also be relevant for terrestrial clinical care such as radiation oncology.

A Review of Orthopaedic Surgical Set-Up and Introduction of the TULIPS Mnemonic - Six Simple Steps for Optimising Set-Up in Orthopaedic Surgery.

Conducting a thorough check to ensure that all equipment and personnel are positioned correctly at the start of any operation is essential for both the safety of the surgical team and the patient outcome. Orthopaedic surgery in particular carries a high risk of occupational injury and this group could benefit greatly from ergonomic improvements. This review highlights multiple factors that can influence safety of surgeons, surgical efficiency and patient outcomes. "TULIPS" is a mnemonic that lists six key steps in optimising the surgical procedure through effective positioning of equipment and personnel pre-operatively. This was trialled by distribution amongst orthopaedic registrars regionally and it received excellent feedback, with the majority changing their current practice. Here we report that using this simple and memorable checklist can assist orthopaedic surgeons in setting up the operating theatre, facilitating ergonomic improvements that can reduce the risk of musculoskeletal injury and radiation exposure.

Cancer stem cell plasticity in glioblastoma multiforme: a perspective on future directions in oncolytic virotherapy.

The cancer stem cell (CSC) hypothesis suggests that a rare population of stem-like cells underpin tumorigenesis. Oncolytic viruses (OVs) demonstrate novel mechanisms of targeting the elusive CSCs with greater selectivity - promising therapeutic potential against solid tumors such as glioblastoma (GBM) that are resistant to conventional treatment. In general, OVs have failed to translate the efficacy from bench to bedside. The success of OVs rely on the hypothesis that eliminating CSCs is key to preventing recurrence. However, newly emerging evidence of CSC plasticity challenge this hypothesis by proposing that the CSC pool can be regenerated from non-CSCs post-treatment. We review this evidence surrounding the CSC hypothesis to propose an original perspective on why several advanced OVs may be failing to reflect their true potential in clinical trials. We argue that preventing non-CSC to CSC dedifferentiation may be critical to achieving long-term treatment efficacy in future OV clinical trials.

Laparoscopy, dorsal lumbotomy and flank incision live donor nephrectomy: comparison of donor outcomes.

BACKGROUND: Flank incision (FL), dorsal lumbotomy (DL) and laparoscopic surgery have been effective approaches to donor nephrectomy. While laparoscopic donor nephrectomy (LDN) has become increasingly popular, there has yet to be a direct comparison of the three modalities. METHODS: We performed a retrospective chart review of FL, DL and LDN operations between 2002 and 2010 within a single institution. Donor and recipient characteristics, as well as surgical outcomes, were assessed. RESULTS: There were 496 donor nephrectomy operations available for analyses. Patients in the LDN group had the lowest estimated blood loss, compared to the DL and FL groups (p < 0.001), lowest rate of complications (p < 0.01), and shortest hospital stay (p < 0.0001). Donors who underwent DL used an average of 60.12 ± 5.0 mg of morphine, which was significantly less than that used by patients in the LDN (93.2 mg, p < 0.0001) and FL (111.82 mg, p < 0.001) groups. Mean serum creatinine of recipients at day 1 post-op was the highest in the FL group (p < 0.0001 FL vs. LDN, p < 0.001 FL vs. DL), but there were no significant differences between the three groups at 2 weeks, 6, 12, 18, and 24 months post-operation (p > 0.45). CONCLUSIONS: Although a lower pain experience of LDN was not indicated, the use of LDN should be favoured over DL and FL as it is associated with fewer complications, and shorter length of stay. Of note, DL appears to be associated with higher complications and is likely not a preferred option for donor nephrectomy.

CONTEXTE: L'incision du flanc, la lombotomie dorsale et la laparoscopie sont des techniques efficaces pour une néphrectomie chez un donneur vivant. Même si la laparoscopie a connu une montée en popularité, aucune comparaison directe entre les trois modalités n'a été effectuée. MÉTHODOLOGIE: Nous avons procédé à un examen rétrospectif des dossiers de patients ayant subi une néphrectomie par incision du flanc, par lombotomie dorsale et par laparoscopie entre 2002 et 2010 dans un même établissement. Les caractéristiques des donneurs et des receveurs ainsi que les résultats de la chirurgie ont été évalués. RÉSULTATS: Les analyses ont porté sur 496 néphrectomies. En comparaison avec les donneurs ayant subi une incision du flanc ou une lombotomie dorsale, les donneurs ayant subi une laparoscopie présentaient la perte sanguine estimée la plus faible (p < 0,001), le taux le plus bas de complications (p < 0,01) et la plus courte durée du séjour en hôpital (p < 0,0001). Les donneurs qui ont subi une lombotomie dorsale ont utilisé en moyenne 60,12 ± 5,0 mg de morphine, soit une valeur significativement plus faible que celle notée chez les patients ayant subi une laparoscopie (93,2 mg, p < 0,0001) et une incision du flanc (111,82 mg, p < 0,001). Le taux moyen de créatinine sérique le lendemain de l'intervention était le plus élevé chez les patients ayant subi une incision du flanc p ( < 0,0001 incision du flanc vs laparoscopie, p < 0,001 incision du flanc vs lombotomie dorsale), mais les différences entre les trois groupes n'étaient pas significatives 2 semaines, 6, 12, 18 et 24 mois après l'opération (p > 0,45). CONCLUSIONS: Même si aucune réduction de la douleur n'a été observée avec la laparoscopie, il faut tout de même favoriser le recours à cette technique plutôt qu'à une lombotomie dorsale ou une incision du flanc, car elle est associée à moins de complications et à un séjour plus court en hôpital. Il est à noter que la lombotomie dorsale semble associée à un taux plus élevé de complications et n'est probablement pas une option à privilégier pour une néphrectomie chez un donneur.

Blastomycosis presenting as a nonhealing wound.

A 41-year-old man was referred to the wound clinic for an enlarging 9.5 x 14-cm ulceration of the right upper arm of 8 months' duration. A biopsy was obtained, and fungal stains showed broad-based budding spores typical of blastomycosis. He was treated with oral itraconazole, and the ulcer healed in 2 months. Blastomycosis is a systemic fungal infection acquired by inhalation of the spores of the fungus Blastomyces dermatitidis. Initially a pulmonary infection, the skin is the most common secondary site of involvement. More typically presenting as hyperkeratotic nodules, it may occur as ulcerations. Blastomycosis has significant morbidity and mortality, and in unsuspected or asymptomatic cases, the skin lesions may be the key to successful diagnosis and treatment.

DEK expression in melanocytic lesions.

The diagnosis of malignant melanoma presents a clinical challenge and relies principally on histopathological evaluation. Previous studies have indicated that increased expression of the DEK oncogene, a chromatin-bound factor, could contribute to the development of melanoma and may be a frequent event in melanoma progression. Here, we investigated DEK expression by immunohistochemistry in a total of 147 melanocytic lesions, including ordinary nevi, dysplastic nevi, Spitz nevi, melanoma in situ, primary invasive melanomas, and metastatic melanomas. Most benign nevi (ordinary, dysplastic, and Spitz nevi) were negative or exhibited weak staining for DEK, with only 4 of 49 cases showing strong staining. Similar to benign nevi, melanoma in situ also demonstrated low levels of DEK expression. In contrast, the expression of DEK in primary invasive melanomas was significantly higher than benign nevi (P < .0001). Moreover, DEK expression was significantly increased in deep melanomas (Breslow depth >1 mm) and metastatic melanomas as compared with superficial melanomas (Breslow depth ≤1 mm) (P < .05). Our findings indicate that DEK overexpression may be a frequent event in invasive melanomas, and further augmentation of DEK expression may be associated with the acquisition of ominous features such as deep dermal invasion and metastasis. These data suggest a role of DEK in melanoma progression.

Melanoma proliferation and chemoresistance controlled by the DEK oncogene.

Gain of chromosome 6p is a consistent feature of advanced melanomas. However, the identity of putative oncogene(s) associated with this amplification has remained elusive. The chromatin remodeling factor DEK is an attractive candidate as it maps to 6p (within common melanoma-amplified loci). Moreover, DEK expression is increased in metastatic melanomas, although the functional relevance of this induction remains unclear. Importantly, in other tumor types, DEK can display various tumorigenic effects in part through its ability to promote proliferation and inhibit p53-dependent apoptosis. Here, we report a generalized up-regulation of DEK protein in aggressive melanoma cells and tumors. In addition, we provide genetic and mechanistic evidence to support a key role of DEK in the maintenance of malignant phenotypes of melanoma cells. Specifically, we show that long-term DEK down-regulation by independent short hairpin RNAs resulted in premature senescence of a variety of melanoma cell lines. Short-term abrogation of DEK expression was also functionally relevant, as it attenuated the traditional resistance of melanomas to DNA-damaging agents. Unexpectedly, DEK short hairpin RNA had no effect on p53 levels or p53-dependent apoptosis. Instead, we identified a new role for DEK in the transcriptional activation of the antiapoptotic MCL-1. Other MCL-1-related factors such as BCL-2 or BCL-xL were unaffected by changes in the endogenous levels of DEK, indicating a selective effect of this gene on the apoptotic machinery of melanoma cells. These results provide support for DEK as a long sought-after oncogene mapping at chromosome 6, with novel functions in melanoma proliferation and chemoresistance.

CARMA3/Bcl10/MALT1-dependent NF-kappaB activation mediates angiotensin II-responsive inflammatory signaling in nonimmune cells.

Angiotensin II (Ang II) is a peptide hormone that, like many cytokines, acts as a proinflammatory agent and growth factor. After injury to the liver, the hormone assists in tissue repair by stimulating hepatocytes and hepatic stellate cells to synthesize extracellular matrix proteins and secrete secondary cytokines and by stimulating myofibroblasts to proliferate. However, under conditions of chronic liver injury, all of these effects conspire to promote pathologic liver fibrosis. Much of this effect of Ang II results from activation of the proinflammatory NF-kappaB transcription factor in response to stimulation of the type 1 Ang II receptor, a G protein-coupled receptor. Here, we characterize a previously undescribed signaling pathway mediating Ang II-dependent activation of NF-kappaB, which is composed of three principal proteins, CARMA3, Bcl10, and MALT1. Blocking the function of any of these proteins, through the use of either dominant-negative mutants, RNAi, or gene targeting, effectively abolishes Ang II-dependent NF-kappaB activation in hepatocytes. In addition, Bcl10(-/-) mice show defective hepatic cytokine production after Ang II treatment. Evidence also is presented that this pathway activates NF-kappaB through ubiquitination of IKKgamma, the regulatory subunit of the IkappaB kinase complex. These results elucidate a concrete series of molecular events that link ligand activation of the type 1 Ang II receptor to stimulation of the NF-kappaB transcription factor. These findings also uncover a function of the CARMA, Bcl10, and MALT1 proteins in cells outside the immune system.