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Colchicine is an alkaloid drug used in multiple medical conditions. It has a narrow therapeutic index, and gastrointestinal symptoms can occur at the beginning or after long-term therapy. Unintentional toxicity is common and has a high mortality rate when missed. Histopathologic recognition is challenging, and timely identification is conducted to improve patients' outcomes. We describe the case of a 77-year-old female who presented to the emergency room for dehydration, longstanding diarrhea, and weight loss. Upper and lower endoscopies showed erythematous mucosa without bleeding in the gastric antrum and an unremarkable duodenum and colon. Duodenal biopsies demonstrated partial villous atrophy with elongated glands and numerous arrested ring mitoses, consistent with colchicine toxicity.

Cancer therapy-induced oral mucositis is a frequent major oncological problem, secondary to cytotoxicity of chemo-radiation treatment. Oral mucositis commonly occurs 7–10 days after initiation of therapy; it is a dose-limiting side effect causing significant pain, eating difficulty, need for parenteral nutrition and a rise of infections. The pathobiology derives from complex interactions between the epithelial component, inflammation, and the oral microbiome. Our longitudinal study analysed the dynamics of the oral microbiome (bacteria and fungi) in nineteen patients undergoing chemo-radiation therapy for oral and oropharyngeal squamous cell carcinoma as compared to healthy volunteers. The microbiome was characterized in multiple oral sample types using rRNA and ITS sequence amplicons and followed the treatment regimens. Microbial taxonomic diversity and relative abundance may be correlated with disease state, type of treatment and responses. Identification of microbial-host interactions could lead to further therapeutic interventions of mucositis to re-establish normal flora and promote patients’ health. Data presented here could enhance, complement and diversify other studies that link microbiomes to oral disease, prophylactics, treatments, and outcome.

Background MUTYH‐associated polyposis is a rare disorder resulting from mutations involved in DNA mismatch repair. This results in an increased susceptibility to colonic adenomatosis and other cancers. Studies have examined the resulting frequency of extracolonic manifestations; however, these typically occur alone, concurrently, or temporally separate from an already diagnosed colorectal cancer in individuals with a biallelic mutation. Case Reported here is a case of five distinct primary neoplasms presenting simultaneously in a patient monoallelic for an MYH mutation. These neoplasms included squamous cell carcinoma of the vulva, rectal adenocarcinoma, synchronous anal adenocarcinoma, papillary thyroid carcinoma, and ovarian serous psammocarcinoma. Throughout her course, she underwent multiple surgical procedures, neoadjuvant chemoradiation, with further adjuvant therapy, and treatment ongoing. Due to her unique presentation, she underwent genetic testing that demonstrated she was monoallelic for an MYH mutation. Conclusion The patient had a positive response to her treatment and surgical procedures with ongoing adjuvant therapy. She will continue to undergo further genetic testing, and testing for her children is being considered. This case demonstrates a unique presentation associated with a monoallelic MYH mutation that is not described in the current literature and warrants further investigation.

Background Acute kidney injury (AKI) is associated with a severe decline in kidney function caused by abnormalities within the podocytes' glomerular matrix. Recently, AKI has been linked to alterations in glycolysis and the activity of glycolytic enzymes, including pyruvate kinase M2 (PKM2). However, the contribution of this enzyme to AKI remains largely unexplored. Methods Cre-loxP technology was used to examine the effects of PKM2 specific deletion in podocytes on the activation status of key signaling pathways involved in the pathophysiology of AKI by lipopolysaccharides (LPS). In addition, we used lentiviral shRNA to generate murine podocytes deficient in PKM2 and investigated the molecular mechanisms mediating PKM2 actions in vitro. Results Specific PKM2 deletion in podocytes ameliorated LPS-induced protein excretion and alleviated LPS-induced alterations in blood urea nitrogen and serum albumin levels. In addition, PKM2 deletion in podocytes alleviated LPS-induced structural and morphological alterations to the tubules and to the brush borders. At the molecular level, PKM2 deficiency in podocytes suppressed LPS-induced inflammation and apoptosis. In vitro, PKM2 knockdown in murine podocytes diminished LPS-induced apoptosis. These effects were concomitant with a reduction in LPS-induced activation of β-catenin and the loss of Wilms’ Tumor 1 (WT1) and nephrin. Notably, the overexpression of a constitutively active mutant of β-catenin abolished the protective effect of PKM2 knockdown. Conversely, PKM2 knockdown cells reconstituted with the phosphotyrosine binding–deficient PKM2 mutant (K433E) recapitulated the effect of PKM2 depletion on LPS-induced apoptosis, β-catenin activation, and reduction in WT1 expression. Conclusions Taken together, our data demonstrates that PKM2 plays a key role in podocyte injury and suggests that targetting PKM2 in podocytes could serve as a promising therapeutic strategy for AKI. Trial registration Not applicable. 66jzd3p7x7ZtqB-vdEamwa Video abstract

Groove pancreatitis is an uncommon, yet well-described, type of focal chronic pancreatitis, affecting “the groove”—the area between the head of the pancreas, the duodenum, and the common bile duct. Men aged 40 to 50 years are most commonly affected, with a history of alcohol abuse frequently disclosed. Clinical manifestations are similar to other forms of chronic pancreatitis, and vomiting secondary to duodenal stenosis is the main feature. It is postulated that pancreatitis in the groove area arises from obstruction of pancreatic juices in the ductal system, causing fibrosis and stasis with resultant inflammation of surrounding structures. The minor papilla is frequently the anatomic area of preferential involvement. Groove pancreatitis poses diagnostic challenges, forming a “pseudotumor” that mimics pancreatic carcinoma. The distinction is important, although often impossible to make because of their similar presentation, with groove pancreatitis usually affecting younger patients. Most patients are successfully treated with pancreaticoduodenectomy when definitive pathologic diagnoses can be made.

Phyllodes tumors of the vulva are rare proliferations that share morphologic similarities with breast neoplasms. Their histogenetic origin is elusive and may be associated with specialized mammary-like glands of the vulva. Because of their rarity, the clinical and pathologic features, classification, and therapy are not well defined, and their biologic behavior is difficult to predict by histology alone. Immunohistochemical expression of estrogen and progesterone receptors and breast markers provide further support for a common origin. Surgical resection is the current mainstay of therapy and is definitive in most cases.

Spindle cell rhabdomyosarcoma is a rare variant of embryonal rhabdomyosarcoma that has a predilection for young males and most commonly involves the paratesticular region followed by head and neck. Histopathology demonstrates elongated spindle cells with fusiform to cigar-shaped nuclei and indistinct eosinophilic cytoplasm arranged in fascicles or whorls. Although the tumor demonstrates increased cellularity and moderate atypia, the microscopic and architectural patterns can allow this tumor to be confused with multiple entities, such as leiomyosarcoma, spindle cell carcinoma, desmoplastic melanoma, or fibrosarcoma, with important therapeutic implications. Immunohistochemical workup demonstrates sarcomeric differentiation with reactivity for desmin, myogenin, and MyoD1 markers. Compared with other subtypes, the spindle cell variant in children is associated with a favorable outcome; however, in the adult population there does not appear to be any prognostic advantage.

Ameloblastoma is an odontogenic tumor with a variety of histologic appearances and an unpredictable biologic behavior. Little is known about allelic losses of tumor suppressor genes in ameloblastomas. This study surveyed DNA damage in ameloblastomas and correlated this with histologic sub-type and clinical outcome. There were 12 ameloblastomas (two peripheral, eight solid, and two unicystic) and three ameloblastic carcinoma studied for loss of heterozygosity of tumor suppressor genes on chromosomes 1p, 3p, 9p,10q, and 17p (L-myc, hOGG1, p16, pten, and p53). The frequency of allelic loss and the intratumoral heterogeneity were calculated. L-myc (71% frequency of allelic loss) and pten (62% frequency of allelic loss) had the most frequent allelic losses. Overall frequency of allelic loss and intratumoral heterogeneity were higher in mandibular and in unicystic tumors and lower in tumors that recurred/metastasized. The rate of allelic loss in the three carcinomas was similar to that seen in benign tumors. The frequency of allelic loss and intratumoral heterogeneity did not correlate with age, gender, histologic subtype, or prognosis. Since tumors that behaved aggressively did not harbor more allelic losses, it is likely that DNA damage in ameloblastomas and ameloblastic carcinomas is sporadic and cumulative. We conclude that other genetic or epigenetic mechanisms may be responsible for malignant behavior in ameloblastic carcinomas.